Supplementary Information for Gold-catalyzed

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Feb 2, 2018 - 1b is poor (Supplementary Table 1, entry 6); the reaction ...... 4.13 (q, J = 7.1 Hz, 2H, OCH2), 2.48-2.36 (m, 2H, CH2), 2.35-2.22 (m, 2H, CH2), ...... CH), 3.59 (t, J = 6.5 Hz, 2H, CH2), 2.44 (d, J = 2.4 Hz, 1H, ≡CH), 2.08 (s, 3H, CH3), ...... 2.463. 2.456. 2.433. 2.404. 2.378. 2.353. 2.346. 2.324. 2.304. 2.282.

Supplementary Information for Gold-catalyzed Stereoselective Cycloisomerization of Allenoic Acids for Two Types of Common Natural γ-Butyrolactones

Zhou et al.

Supplementary Methods Materials: 1

H and 13C nuclear magnetic resonance spectra were recorded with an instrument

operated at 300 MHz for 1H NMR spectra and 75 MHz for 13C NMR spectra. CDCl3 was used as solvent in all NMR experiments. Chemical shifts (δ) are given in parts per million (ppm). Infrared spectra were recorded from the films of pure samples on sodium chloride plates on a FT-IR spectrometer. Mass and HRMS spectra were carried out in EI or ESI mode. Flash column chromatography was performed on silica gel H. Dioxane and THF were refluxed over sodium wire using diphenyl ketone as indicator and distilled right before use. CuBr2 was purchased from J & K. (S)-α,α-diphenylprolinol and (R)-α,α-diphenylprolinol were purchased from Shanghai Darui Fine Chemicals. Aldehydes were distilled right before use. AgOTs was purchased from Alfa Aesar. CBr4 used was recrystallized from EtOH, washed with ethyl ether, and dired by vacuum. Other commercially available reagents were purchased and used as received.

Synthesis of enantioenriched 4-allenoic acids. Enantioselective allenylation of terminal alkynes 1a with aldehyde 2a in the presence of amine (S)-3a (EATA) afforded the desired product (Ra)-4aa in 36% yield with 95% ee in a sealed tube at 130 oC for 15 h (Supplementary Table 1, entry 1).1 With 1.1 equiv. of benzyl pent-4-ynoate 1a, the yield of (Ra)-4aa was improved to 38% albeit with 94% ee (Supplementary Table 1, entry 2). By replacing benzyl pent-4-ynoate 1a with ethyl pent-4-ynoate 1b, the yield of 4,5-dienoate (Ra)-4ba was improved to 53% but ee dropped to 85% (Supplementary Table 1, entry 3). We then screened the effect of the loading of 1b, showing that 1.2 equiv. are the best (Supplementary Table 1, entries 4 and 5). The yield for the reaction at 120 oC in the sealed tube with 1.2 equiv. 1b is poor (Supplementary Table 1, entry 6); the reaction under reflux at 120 oC afforded (Ra)-4ba in 46% yield with 96% ee (Supplementary Table 1, entries 7-11). Thus, the optimal reaction conditions were established as follows: 20 mol% CuBr2, alkyne 1b/aldehyde 2a/amine (S)-3a = 1.2/1.5/1 in dioxane

1

under reflux (Supplementary Table 1, entry 7).

Supplementary Table 1 Synthesis of 4,5-allenoatea (Ra)-4aa and (Ra)-4ba a

1

T/oC

entry

a

(Ra)-4 yield b (%)

ee c (%)

130 d

36 ((Ra)-4aa)

95

1.1

130 d

38 ((Ra)-4aa)

94

Et (1b)

1.1

130 d

53 ((Ra)-4ba)

85

4

Et (1b)

1.2

130 d

60 ((Ra)-4ba)

93

5

Et (1b)

1.4

130 d

63 ((Ra)-4ba)

91

6

Et (1b)

1.2

120 d

49 ((Ra)-4ba)

93

7

Et (1b)

1.2

120 e

46 ((Ra)-4ba)

96

8

Et (1b)

1.1

120 e

37 ((Ra)-4ba)

95

9

Et (1b)

1.3

120 e

44 ((Ra)-4ba)

94

10

Et (1b)

1.4

120 e

47 ((Ra)-4ba)

96

11

Et (1b)

1.5

120 e

45 ((Ra)-4ba)

93

R

X (equiv.)

1

Bn (1a)

1.5

2

Bn (1a)

3

The reactions were conducted on a 1.0 mmol of (S)-3a in 3 mL of dioxane with 1.5 equiv. 2a

under nitrogen atmosphere.

b

c

Isolated yield. Determined by chiral HPLC analysis of isolated

product. d Reactions were conducted in a sealed tube. e Reactions were conducted under reflux under N2 atmosphere.

Then a series of 4-allenoic acids (Ra)-5 were prepared by treating the corresponding carboxylates (Ra)-4 with 1.5 equiv. of LiOH∙H2O in EtOH/H2O under reflux at 90 oC (Supplementary Table 2).

2

Supplementary Table 2 Synthesis of 4-allenoic acids (Ra)-5 a

2

a

(Ra)-5

t1

Entry

t2 (h)

yield b (%)

ee c (%)

8

40 ((Ra)-5a)

96

18

8

38 ((Ra)-5b)

97

n-C11H23 (2c)

17

19

46 ((Ra)-5c)

97

4e

i-Pr (2d)

15.5

12

24 ((Ra)-5d)

98

5

Cy (2e)

15

18

34 ((Ra)-5e)

97

6

Bn (2f)

17

12

34 ((Ra)-5f)

96

7

BnCH2 (2g)

17.5

18

45 ((Ra)-5g)

96

8

CH2=CH(CH2)8 (2h)

19

18

40 ((Ra)-5h)

96

9f

TBSCC(CH2)6 (2i)

18

5

42 ((Ra)-5i)

97

R

(h)

1

n-C7H15 (2a)

15

2d

n-C4H9 (2b)

3

The reactions were conducted on a 15 mmol scale of (S)-3a with 1.2 equiv. 1b and 1.5 equiv. 2 b

c

under nitrogen atmosphere. Combined yield of 2 steps. Determined by chiral HPLC analysis of d

the corresponding carboxylate of (Ra)-5. The reaction was conducted on a 25 mmol scale of e

f

(S)-3a. The reaction was conducted on a 20 mmol scale of (S)-3a. The reaction was conducted on a 7 mmol scale; Hydrolysis under a mild condition: 1.0 equiv. of LiOH∙H2O in THF/MeOH/H2O = 1:1:1 at room temperature for 5 h.

Optimization of the lactonization reaction for gram scale synthesis For gram scale synthesis of (E)-6, further adjustments for the temperature of the lactonization reaction were conducted to improve the E/Z selectivity: runing the reaction at 0 oC made no difference as compared with tht at 25 oC (Supplementary Table 3, entries 1-2), while the reaction at -20 oC gave a higher selectivity (E/Z = 98:2) (Supplementary Table 3, entry 3); when the reaction was conducted at -40 oC, a result

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of 99:1 E/Z selectivity in 44% yield with 56% recovery of acid 5b was observed (Supplementary Table 3, entry 4). Thus, we defined the reaction temperature as -20 o

C.

Supplementary Table 3 Further optimization of the reaction conditions for racemic (E)-6b

a

a

6b

Entry

T (oC)

t (h)

1

25

2

NMR yield b (%)

E/Z b

3

100

96/4

0

12

100

97/3

3

-20

12

100

98/2

4c

- 40

17

44

99/1

AgOTs, AuCl(LB-Phos), and CHCl3 (2 mL) were stirred for 15 min under nitrogen atmosphere;

then 0.2 mmol 5b and CHCl3 (1 mL) were added.

b

1

Determined by H NMR of crude product

using 1,3,5-trimethylbenzene as internal standard. c 56% recovery of 5b was detected.

Optimization of the the synthesis of rac-xestospongiene Under the optimized conditions, the Au-catalyzed lactonization reaction of rac-5k was executed to afford racemic xestospongiene (6k) with an E/Z selectivity of 94:6 (Supplementary Table 4, entry 1). The reaction at -30 oC for 31 h led to an E/Z selectivity of 97:3 but with 11% rac-5k being recovered (Supplementary Table 4, entry 2); further lowering the temperature to -40 oC couldn’t make a better selectivity while more starting acid rac-5k was recovered even after 36 h (Supplementary Table 4, entry 3). Then, we tried to increase the loading of the catalysts. When the reaction at -20 oC with 10 mol% catalysts, 6k was formed in 99% NMR yield with a E/Z

4

selectivity of 96:4 after 20 h (Supplementary Table 4, entry 4); Reducing the temperature to -30 oC with 10 mol% catalysts gave 6k a higher 97:3 selectivity with no rac-5k recovered after 24 h (Supplementary Table 4, entry 5). Thus, we defined 10 mol% catalyst at -30 oC for 24 h as the standard reaction conditions.

Supplementary Table 4 Optimization of the reaction conditions for the cyclization of rac-5k a

rac-5k

6k Entry

a

X mol%

o

T ( C)

t (h)

b

NMR yield (%)

E/Z

b

recovery b (%)

1c

5

22

2.5

100

94:6

0

2

5

-30

31

88

97:3

11

3

5

-40

36

90

97:3

10

4d

10

-20

20

99

96:4

0

5

10

-30

24

97

97:3

0

AgOTs, AuCl(LB-Phos), and CHCl3 (2 mL) were stirred for 15 min under nitrogen atmosphere; b

1

then 0.2 mmol rac-5k and CHCl3 (1 mL) were added. Determined by H NMR of the crude c

product using 1,3,5-trimethylbenzene as internal standard. The reaction was conducted on a 1.0 mmol scale of rac-5k in 10 mL of CHCl3 under N2 atomosphere. d The reaction was conducted on a 0.1 mmol scale of rac-5k in 1.5 mL of CHCl3 under N2 atomosphere.

Kinetic resolution of racemic 8: synthesis of optically active propargylic alcohols (R)-8 and (S)-8 A

novozym-435-catalyzed

kinetic

resolution

of

9-((tert-butyldimethylsilyl)oxy)non-1-yn-3-ol 8 with vinyl acetate was studied and some typical results are presented in Supplementary Table 5. We ran the reaction under the reported conditions initially:2 The treatment of racemic propargylic alcohol

5

8 with 10 w% novozym-435-catalyzed in 3 mL of vinyl acetate at 60 oC for 2.75 h afforded propargylic acetate (S)-11 in 33% NMR yield with 93 % ee and 66% NMR yield of propargylic alcohol (R)-8 (Supplementary Table 5, entry 1); shorten the time to 1.5 h led to a slightly higher ee of 94% for (S)-11 but a lower 21% yield (Supplementary Table 5, entry 2); prolonging the time to the point when acetate (S)-11 and alcohol (R)-8 were approximately equal in yield didn’t give a better ee (Supplementary Table 5, entry 3); further extending the time to 19.5 h made the yield of (S)-11 55% with 81 % ee and 45% of alcohol (R)-8 recovered in 79% ee (Supplementary Table 5, entry 4). Then the loadings of enzyme and vinyl acetate were also screened (Supplementary Table 5, entries 5-7). The ee of (S)-11 was improved to 95% with an increased yield of 37% when temperature went down to 30 oC (Supplementary Table 5, entry 8). 20% w of the catalyst used for the reaction at this temperature for 6 h led to a better result of 41% yield of acetate (S)-11 with 99% ee (Supplementary Table 5, entry 9).

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Supplementary Table 5 Novozym-435-catalyzed kinetic resolution of racemic 8 a.

(S)-11

Entry T (oC) X (% w)b V (mL) t (h)

a

(R)-8

yieldc (%) eed (%) yieldc (%) eee (%)

1

60

10

3

2.75

33

93

66

-

2

60

10

3

1.5

21

94

77

-

3

60

10

3

11

51

86

49

86

4

60

10

3

19.5

55

81

45

79

5

60

20

3

2.75

41

89

51

-

6

60

20

6

2.75

30

91

64

-

7

60

20

6

1.75

28

93

71

-

8

30

10

3

9

37

95

60

-

9

30

20

3

6

41

99f

59

-

b

c

1

Reactions were conducted on a 0.5 mmol scale of rac-8. % by weight. Determined by H

NMR of the crude product using 1,3,5-trimethylbenzene as internal standard.

d

Determined by

chiral HPLC analysis of isolated acetate (S)-11. e Determined by chiral HPLC analysis of acetate of isolated alcohol (R)-8. f Determined by chiral GC analysis of isolated acetate (S)-11.

On the basis of these observations, we set out to explore how to get higher ees of (S)-11 and alcohol (R)-8 at the same time. For this purpose, we identified n-hexane as the solvent with the addition of different amounts of vinyl acetate for the reaction at 30 oC. Fortunately, when 20 w% of enzyme was used with 5.2 equiv. of vinyl acetate in n-hexane for 11.5 h, ee of (R)-8 reached 97% in 44% yield along with 93% ee of (S)-11 in 46% yield (Supplementary Table 6, entry 1). Reducing the reaction time to 2.5 h failed to give a better ee of (S)-11 (Supplementary Table 6, entry 2) (compare with the best result showed in Supplementary Table 5); we then prolonged the reaction time to 19 h, affording (R)-8 with 98% ee and 47% yield (Supplementary Table 6, entry 3).

7

Supplementary Table 6 Further optimization of Novozym-435-catalyzed kinetic resolution of 8 a

(S)-11

a

Entry

T (h)

1

(R)-8

yield b (%)

ee c (%)

yield b (%)

ee d (%)

11.5

46

93

44

97

2

2.5

35

97

44

-

3

19

50

92

47

98

b

1

Reactions were conducted on a 0.5 mmol scale of rac-8 at 30 oC. Determined by H NMR of

the crude product using 1,3,5-trimethylbenzene as internal standard. c Determined by chiral HPLC analysis of isolated acetate (S)-11.

d

Determined by chiral HPLC analysis of acetate of isolated

alcohol (R)-8.

Synthesis of enantioenriched 4-allenoic acids 1. Synthesis of (Ra)-benzyl 4,5-tridecadienoate (Ra)-4aa (zj-8-078)

To a flame-dried Schlenk tube with a polytetrafluoroethylene plug were added CuBr2 (0.0462 g, 0.2 mmol, 98%), (S)-3a (0.2582 g, 1 mmol,98%), 1a (0.2824 g, 1.5 mmol)/dioxane (2 mL), and octaldehyde 2a (0.1927 g, 1.5 mmol)/dioxane (1 mL) sequentially under nitrogen atmosphere. The Schlenk tube was then sealed with screwing the polytetrafluoroethylene plug tightly. The reaction was complete after being stirred in an oil bath preheated at 130 oC for 15 h as monitored by TLC. The mixture was filtrated through a short column of silica gel [eluent: Et2O (10 mL × 3)] and then washed with an aqueous solution of hydrochloric acid (3 M, 10 mL × 3). The organic layer was separated and the aqueous layer was extracted with Et2O (10 mL).

8

The combined organic layer was washed with brine and dried over anhydrous Na2SO4. After filtration and evaporation, the residue was purified by chromatography [eluent: petroleum ether (60-90 oC)/ diethyl ether = 100/1 (600 mL)] on silica gel to afford (Ra)-4aa (0.1089 g, 36%) as a liquid: 95% ee (HPLC conditions: Chiralcel OJ-H column, n-hexane/i-PrOH = 200/1, 0.8 mL/min, λ = 214 nm, tR (major) = 9.6 min, tR (minor) = 8.5 min); [α]D20 = -54.5 (c = 1.01, CHCl3); 1H NMR (300 MHz, CDCl3) δ 7.45-7.25 (m, 5H, Ar-H), 5.19-5.04 (m, 4H, =CH × 2 + CH2), 2.53-2.41 (m, 2H, CH2), 2.37-2.25 (m, 2H, CH2), 2.00-1.87 (m, 2H, CH2), 1.43-1.18 (m, 10H, CH2 × 5), 0.87 (t, J = 6.8 Hz, 3H, CH3); 13C NMR (75 MHz, CDCl3) δ 203.6, 172.8, 135.9, 128.4, 128.1, 128.0, 92.5, 89.3, 60.0, 33.3, 31.7, 29.03, 28.99, 28.7, 23.7, 22.5, 14.0; IR (neat) ν (cm−1) 3093, 3066, 3034, 2955, 2926, 2855, 1962, 1740, 1498, 1456, 1380, 1353, 1256, 1154, 1002; MS (70 ev, EI) m/z (%) 301 (M+ + 1, 2.36), 300 (M+, 2.56), 167 (100), 91 (100); HRMS calcd for C20H28O2 [M+]: 300.2089, found: 300.2090.

2. Synthesis of (Ra)-4,5-tridecadienoic acid (Ra)-5a (zj-8-039, 8-040)

Typical Procedure I: To a dry Schlenk flask were added CuBr2 (0.6768 g, 3 mmol, 99%), (S)-2-(diphenylhydroxymethyl)pyrrolidine (S)-3a (3.8707 g, 15 mmol, 98%), ethyl pent-4-ynoate 1b3 (2.2715 g, 18 mmol)/dioxane (20 mL), and octaldehyde 2a (3.5 mL, d = 0.821 g cm-3, 2.8739 g, 22.45 mmol)/dioxane (10 mL) sequentially under nitrogen atmosphere. After continuous stirring for 15 h under reflux at 120 oC, the reaction was complete as monitored by TLC. Then the resulting mixture was cooled down to room temperature. The mixture was diluted with ether (60 mL) and then washed with an aqueous solution of hydrochloric acid (3 M, 10 mL × 3). The organic layer was separated and the aqueous layer was extracted with Et2O (10 mL). The combined organic layer was washed with brine and dried over anhydrous Na2SO4. After filtration and evaporation, the residue was purified by

9

chromatography [eluent: petroleum ether (60-90 oC)/diethyl ether = 100/1 (500 mL × 3) to 50:1 (300 mL)] on silica gel to afford (Ra)-4ba (1.4870 g) as a liquid, which was then used in the next step without further characterization. Typical Procedure II: To a round-bottom flask were added (Ra)-4ba (1.4870 g, 6.25 mmol, prapared above), EtOH/H2O = 1:1 by volume (pre-mixed by using 31 mL of H2O and 31 mL of EtOH), and LiOH∙H2O (0.4147 g, 9.375 mmol, 95%) sequentially. After continuous stirring for 8 h under reflux at 90 oC, the reaction was complete as monitored by TLC. Then the mixture was cooled down to room temperature. After evaporation to remove EtOH, the resulting mixture was acidified with an aqueous solution of hydrochloric acid (aq., 3.0 M) until pH = 1 and extracted with Et2O (20 mL × 3). The combined organic layer was washed with brine and dried over anhydrous Na2SO4, filtration, evaporation, and column chromatography on silica gel gave (Ra)-5a4 (1.2547 g, 40%, 2 steps) [eluent: petroleum ether (60-90 oC)/ ethyl acetate = 15/1 (480 mL) to 10:1 (600 mL) to 5:1 (300 mL)] as an oil: 96% ee (determined by the corrsponding esterification product (R)-ethyl trideca-4,5-dienoate (Ra)-4ba); [α]D20 = -70.1 (c = 1.00, CHCl3); 1H NMR (300 MHz, CDCl3) δ 11.21 (bs, 1H, COOH), 5.27-5.04 (m, 2H, =CH × 2), 2.48 (t, J = 7.5 Hz, 2H, CH2), 2.36-2.23 (m, 2H, CH2), 2.03-1.90 (m, 2H, CH2), 1.45-1.18 (m, 10H, CH2 × 5), 0.88 (t, J = 6.8 Hz, 3H, CH3);

13

C NMR (75 MHz, CDCl3) δ 203.7, 179.7, 92.9, 89.2, 33.1, 31.8, 29.1,

28.8, 23.5, 22.6, 14.1; IR (neat) ν (cm−1) 3582-2257 (COOH), 3031, 2957, 2926, 2855, 2662, 1963, 1713, 1436, 1412, 1378, 1335, 1277, 1249, 1211, 1173, 1077; MS (70 ev, EI) m/z (%) 210 (M+, 4.49), 126 (100).

Esterification for determination of the ee value of (Ra)-5a: synthesis of (Ra)-ethyl 4,5-tridecadienoate (Ra)-4ba5 (zj-8-043)

Typical Procedure III: To a Schlenk tube were added (Ra)-5a (0.0846 g, 0.4 mmol, prapared above) and DMF (4 mL). Then K2CO3 (0.1657 g, 1.2 mmol) and EtI

10

(0.04 mL, d = 1.94 g cm-3, 0.0768 g, 0.49 mmol, 99%) were added sequentially. After continuous stirring at room temperature for 8 h, the reaction was complete as monitored by TLC. After quenching with water (10 mL) and being stirred for 10 min, the aqueous solution was extracted with Et2O (15 mL × 3). The combined organic layer was washed with H2O then brine and dried over anhydrous Na2SO4. Filtration, evaporation, and column chromatography on silica gel gave (Ra)-4ba (0.0917 g, 96%) [eluent: petroleum ether (60-90 oC)/ ethyl acetate = 50/1 (450 mL)] as a liquid: 96% ee (HPLC conditions: Chiralcel OD-H column, n-hexane, 0.5 mL/min, λ = 214 nm, tR (major) = 15.8 min, tR (minor) = 15.4 min); [α]D20 = -61.9 (c = 0.99, CHCl3); 1H NMR (300 MHz, CDCl3) δ 5.30-4.95 (m, 2H, =CH × 2), 4.13 (q, J = 7.1 Hz, 2H, OCH2), 2.45-2.34 (m, 2H, CH2), 2.34-2.23 (m, 2H, CH2), 2.02-1.88 (m, 2H, CH2), 1.44-1.18 (m, 13H, CH2 × 5 + CH3), 0.88 (t, J = 6.6 Hz, 3H, CH3); 13C NMR (75 MHz, CDCl3) δ 203.6, 173.0, 92.4, 89.4, 60.1, 33.3, 31.7, 29.03, 28.99, 28.8, 23.8, 22.5, 14.1, 13.9; IR (neat) ν (cm−1) 2958, 2926, 2855, 1962, 1739, 1464, 1446, 1421, 1372, 1349, 1300, 1259, 1195, 1158, 1133, 1096, 1077, 1039; MS (70 ev, EI) m/z (%) 238 (M+, 5.49), 80 (100); HRMS calcd for C15H26O2 [M+]: 238.1933, found: 238.1933.

3. Synthesis of (Ra)-4,5-decadienoic acid (Ra)-5b (zj-6-047, 6-053)

Typical Procedure IV: To a dry Schlenk flask were added CuBr2 (1.1261 g, 5.0 mmol, 99%), (S)-3a (6.4555 g, 25 mmol, 98%), 1b (3.7875 g, 30 mmol)/dioxane (30 mL), and valeraldehyde 2b (4.0 mL, d = 0.81 g cm-3, 3.24 g, 37.67 mmol)/dioxane (15 mL) sequentially under nitrogen atmosphere. After continuous stirring for 18 h under reflux at 120 oC, the reaction was complete as monitored by TLC. Then the resulting mixture was cooled down to room temperature. The mixture was filtrated through a short column of silica gel [eluent: Et2O (25 mL × 3)], and then washed with an aqueous solution of hydrochloric acid (3 M, 10 mL × 3). The organic layer was

11

separated and the aqueous layer was extracted with Et2O (10 mL). The combined organic layer was washed with brine and dried over anhydrous Na2SO4. After filtration and evaporation, the residue was purified by chromatography [(eluent: petroleum ether (60-90 oC)/diethyl ether = 100/1 (500 mL × 2) to 50/1 (500 mL × 2)] on silica gel to afford (Ra)-4bb (2.0071 g) as a liquid, which was then used in the next step without further characterization. Following Typical Procedure II, the reaction of (Ra)-4bb (2.0071 g, 10.2 mmol, prepared above), EtOH/H2O = 1:1 by volume (pre-mixed by using 50 mL of H2O and 50 mL of EtOH), and LiOH·H2O (0.6768 g, 15.3 mmol, 95%) at 90 oC for 8 h afforded (Ra)-5b (1.6152 g, 38%, 2 steps) [(eluent: petroleum ether (60-90 oC)/ethyl acetate = 10/1 (550 mL) to 8/1 (540 mL) to 5/1 (600 mL)] as an oil: 97% ee (determined by the corrsponding esterification product (Ra)-4bb); [α]D20 = -77.3 (c = 0.995, CHCl3); 1H NMR (300 MHz, CDCl3) δ 11.42 (bs, 1H, COOH), 5.26-5.08 (m, 2H, =CH × 2), 2.48 (t, J = 7.4 Hz, 2H, CH2), 2.36-2.23 (m, 2H, CH2), 2.06-1.90 (m, 2H, CH2), 1.45-1.24 (m, 4H, CH2 × 2), 0.90 (t, J = 7.2 Hz, 3H, CH3); 13C NMR (75 MHz, CDCl3) δ 203.7, 179.9, 92.8, 89.2, 33.1, 31.2, 28.5, 23.5, 22.1, 13.8; IR (neat) ν (cm−1) 3699-2161 (COOH), 3031, 2958, 2928, 2871, 2863, 2668, 1963, 1711, 1436, 1412, 1377, 1333, 1274, 1247, 1211, 1173; MS (70 ev, EI) m/z (%) 169 (M+ + 1, 2.39), 168 (M+, 5.55), 126 (100); HRMS calcd for C10H16O2 [M+]: 168.1150, found: 168.1148.

Esterification for determination of the ee value of (Ra)-5b: synthesis of (Ra)-ethyl 4,5-decadienoate (Ra)-4bb (zj-6-055)

Following Typical Procedure III, the reaction of (Ra)-5b (0.0839 g, 0.5 mmol)/DMF (5 mL), EtI (0.05 mL, d = 1.94 g cm-3, 0.0951 g, 0.61 mmol, 98%), and K2CO3 (0.2072 g, 1.5 mmol) for 14 h afforded (Ra)-4bb (0.0924 g, 94%) [eluent: petroleum ether (60-90 oC)/ethyl acetate = 100/1 (500 mL) to 50/1 (300 mL)] as a

12

liquid: 97% ee (HPLC conditions: Chiralcel PC-2 column, n-hexane, 0.7 mL/min, λ = 214 nm, tR (major) = 44.8 min, tR (minor) = 38.4 min); [α]D20 = -68.0 (c = 0.99, CHCl3); 1H NMR (300 MHz, CDCl3) δ 5.18-5.07 (m, 2H, =CH × 2), 4.13 (q, J = 7.1 Hz, 2H, OCH2), 2.47-2.36 (m, 2H, CH2), 2.35-2.23 (m, 2H, CH2), 2.06-1.91 (m, 2H, CH2), 1.44-1.28 (m, 4H, CH2 × 2), 1.26 (t, J = 7.2 Hz, 3H, CH3) 0.90 (t, J = 7.1 Hz, 3H, CH3);

13

C NMR (75 MHz, CDCl3) δ 203.7, 173.0, 92.3, 89.4, 60.1, 33.4, 31.2,

28.5, 23.8, 22.1, 14.1, 13.7; IR (neat) ν (cm−1) 2959, 2929, 2875, 2859, 1963, 1738, 1466, 1444, 1418, 1372, 1350, 1300, 1250, 1159, 1097, 1052, 1033; MS (70 ev, EI) m/z (%) 197 (M+ + 1, 10.80), 196 (M+, 24.87), 81 (100); HRMS calcd for C12H20O2 [M+]: 196.1463, found: 196.1461.

4. Synthesis of (Ra)-4,5-heptadecadienoic acid (Ra)-5c (zj-4-028, 4-033)

Following Typical Procedure IV, the reaction of CuBr2 (0.6767 g, 3.0 mmol, 99%), (S)-3a (3.8698 g, 15 mmol, 98%), 1b (2.2795 g, 18 mmol)/dioxane (15 mL), and n-dodecanal 2c (4.98 mL, d = 0.831 g cm-3, 4.1384 g, 22.49 mmol)/dioxane (10 mL) for 17 h afforded product (Ra)-4bc (1.9936 g) [(eluent: petroleum ether (60-90 oC) (500 mL) to petroleum ether (60-90 oC)/diethyl ether = 100/1 (500 mL × 2)] as a liquid, which was then submitted to next step. Following Typical Procedure II, the reaction of product (Ra)-4bc (1.9936 g, 6.78 mmol, prepared above), EtOH/H2O = 1:1 by volume (pre-mixed by using 33.5 mL of H2O and 33.5 mL of EtOH), and LiOH·H2O (0.4460 g, 10.17 mmol, 95%) for 19 h afforded (Ra)-5c (1.8322 g, 46%, 2 steps) [(eluent: petroleum ether (60-90 oC)/ethyl acetate = 20/1 (500 mL) to 10/1 (500 mL × 3)] as an oil: 97% ee (determined by the corrsponding esterification product (Ra)-4bc); [α]D20 = -56.5 (c = 1.00, CHCl3); 1H NMR (300 MHz, CDCl3) δ 11.39 (bs, 1H, COOH), 5.24-5.07 (m, 2H, =CH × 2), 2.48 (t, J = 7.2 Hz, 2H, CH2), 2.36-2.23 (m, 2H, CH2), 2.04-1.90 (m, 2H, CH2), 1.45-1.18

13

(m, 18H, CH2 × 9), 0.88 (t, J = 6.6 Hz, 3H, CH3); 13C NMR (75 MHz, CDCl3) δ 203.7, 179.9, 92.8, 89.2, 33.1, 31.9, 29.6, 29.5, 29.4, 29.2, 29.1, 28.8, 23.5, 22.7, 14.1; IR (neat) ν (cm−1) 3657-2311 (COOH), 2955, 2924, 2854, 1963, 1712, 1438, 1278, 1210, 1196, 1132, 1077; MS (70 ev, EI) m/z (%) 267 (M+ + 1, 2.88), 266 (M+, 5.98), 126 (100); HRMS calcd for C17H30O2 [M+]: 266.2246, found: 266.2251.

Esterification for determination of the ee value of (Ra)-5c: synthesis of (Ra)-ethyl 4,5-heptadecadienoate (Ra)-4bc (zj-4-111)

Following Typical Procedure III, the reaction of (Ra)-5c (0.1326 g, 0.5 mmol)/DMF (5 mL), EtI (0.05 mL, d = 1.94 g cm-3, 0.0960 g, 0.616 mmol, 99%), and K2CO3 (0.2079 g, 1.5 mmol) for 24 h afforded (Ra)-4bc (0.1355 g, 92%) [eluent: petroleum ether (60-90 oC)/ethyl acetate = 100/1 (500 mL)] as a liquid: 97% ee (HPLC conditions: Chiralcel OD-H column, n-hexane, 0.7 mL/min, λ = 214 nm, tR (major) = 14.2 min, tR (minor) = 13.9 min); [α]D20 = -51.0 (c = 1.00, CHCl3); 1H NMR (300 MHz, CDCl3) δ 5.19-5.07 (m, 2H, =CH × 2), 4.13 (q, J = 7.1 Hz, 2H, OCH2), 2.47-2.37 (m, 2H, CH2), 2.36-2.23 (m, 2H, CH2), 2.02-1.89 (m, 2H, CH2), 1.45-1.15 (m, 21H, CH3 + CH2 × 9), 0.88 (t, J = 6.6 Hz, 3H, CH3); 13C NMR (75 MHz, CDCl3) δ 203.6, 173.1, 92.5, 89.5, 60.2, 33.4, 31.9, 29.6, 29.5, 29.3, 29.1, 28.9, 23.9, 22.6, 14.2, 14.1; IR (neat) ν (cm−1) 2956, 2925, 2854, 1963, 1739, 1466, 1372, 1350, 1300, 1250, 1159, 1097, 1038; MS (70 ev, EI) m/z (%) 294 (M+, 6.39), 80 (100); HRMS calcd for C19H34O2 [M+]: 294.2559, found: 294.2556.

5. Synthesis of (Ra)-7-methyl-4,5-octadienoic acid (Ra)-5d (zj-8-048, 8-051)

Following Typical Procedure I, the reaction of CuBr2 (0.9014 g, 4 mmol, 99%),

14

(S)-3a (5.1672 g, 20 mmol, 98%), 1b (3.7830 g, 30 mmol)/dioxane (35 mL), and isobutaldehyde 2d (2.73 mL, d = 0.79 g cm-3, 2.1567 g, 29.95 mmol)/dioxane (15 mL) for 15.5 h afforded product (Ra)-4bd (0.9565 g, 26% ) [(eluent: petroleum ether (60-90 oC)/diethyl ether = 100/1 (500 mL × 3)] as a liquid: 98% ee (HPLC conditions: Chiralcel OD-H column, n-hexane, 1.0 mL/min, λ = 214 nm, tR (major) = 12.9 min, tR (minor) = 12.2 min); [α]D20 = -66.0 (c = 1.00, CHCl3); 1H NMR (300 MHz, CDCl3) δ 5.26-5.12 (m, 2H, =CH × 2), 4.13 (q, J = 7.2 Hz, 2H, CH2), 2.46-2.36 (m, 2H, CH2), 2.35-2.18 (m, 3H, CH + CH2), 1.26 (t, J = 7.2 Hz, 3H, CH3), 0.99 (d, J = 6.9 Hz, 6H, CH3 × 2); 13C NMR (75 MHz, CDCl3) δ 202.0, 172.9, 99.8, 90.7, 60.1, 33.3, 27.8, 23.8, 22.3, 22.2, 14.1; IR (neat) ν (cm−1) 2961, 2925, 2869, 1961, 1738, 1466, 1447, 1420, 1372, 1350, 1299, 1251, 1227, 1199, 1159, 1097, 1055, 1029; MS (70 ev, EI) m/z (%) 182 (M+, 27.17), 93 (100); HRMS calcd for C11H18O2 [M+]: 182.1307, found: 182.1310. Following Typical Procedure II, the reaction of (Ra)-4bd (0.8194 g, 4.5 mmol, prepared above), EtOH/H2O = 1:1 by volume (pre-mixed by using 22.5 mL of H2O and 22.5 mL of EtOH), and LiOH·H2O (0.2990 g, 6.75 mmol, 95%) for 12 h afforded (Ra)-5d (0.6317 g, 91%) [(eluent: petroleum ether (60-90 oC)/ethyl acetate = 15/1 (480 mL) to 10/1 (550 mL) to 5/1 (600 mL)] as an oil: 98% ee (determined by the corrsponding esterification product (Ra)-4bd); [α]D20 = -71.8 (c = 1.00, CHCl3); 1H NMR (300 MHz, CDCl3) δ 10.90 (bs, 1H, COOH), 5.28-5.16 (m, 2H, =CH × 2), 2.48 (t, J = 7.2 Hz, 2H, CH2), 2.38-2.18 (m, 3H, CH + CH2), 0.99 (d, J = 6.9 Hz, 6H, CH3 × 2); 13C NMR (75 MHz, CDCl3) δ 202.1, 179.9, 100.3, 90.5, 33.1, 27.9, 23.5, 22.4, 22.3; IR (neat) ν (cm−1) 3749-2203 (COOH), 3036, 2961, 2923, 2869, 2661, 1961, 1713, 1412, 1382, 1364, 1297, 1251, 1212, 1169, 1107, 1080, 1049, 1018; MS (70 ev, EI) m/z (%) 154 (M+, 14.69), 67 (100); HRMS calcd for C9H14O2 [M+]: 154.0994, found: 154.0991.

Esterification for determination of the ee value of (Ra)-5d: synthesis of (Ra)-ethyl 7-methyl-4,5-octadienoate (Ra)-4bd (zj-8-063)

15

Following Typical Procedure III, the reaction of (Ra)-5d (0.0773 g, 0.5 mmol)/DMF (5 mL), EtI (0.05 mL, d = 1.94 g cm-3, 0.096 g, 0.616 mmol, 99%), and K2CO3 (0.2075 g, 1.5 mmol) for 11 h afforded (Ra)-4bd (0.0867 g, 95%) [eluent: petroleum ether (60-90 oC)/ethyl acetate = 50/1 (800 mL)] as a liquid: 98% ee (HPLC conditions: Chiralcel OD-H column, n-hexane, 1.0 mL/min, λ = 214 nm, tR (major) = 11.4 min, tR (minor) = 10.8 min); [α]D20 = -66.4 (c = 1.02, CHCl3); 1H NMR (300 MHz, CDCl3) δ 5.28-5.11 (m, 2H, =CH × 2), 4.13 (q, J = 7.2 Hz, 2H, OCH2), 2.45-2.37 (m, 2H, CH2), 2.36-2.18 (m, 3H, CH + CH2), 1.26 (t, J = 7.1 Hz, 3H, CH3), 0.99 (d, J = 6.9 Hz, 6H, CH3 × 2); 13C NMR (75 MHz, CDCl3) δ 202.1, 173.1, 99.9, 90.7, 60.2, 33.3, 27.8, 23.9, 22.4, 22.3, 14.1.

6. Synthesis of (Ra)-6-cyclohexyl-4,5-hexadienoic acid (Ra)-5e (zj-3-175, 3-196)

Following Typical Procedure IV, the reaction of CuBr2 (0.6757 g, 3 mmol, 99%), (S)-3a (3.8745 g, 15 mmol, 98%), 1b (2.2739 g, 18 mmol)/dioxane (17 mL), and cyclohexanaldehyde 2e (2.72 mL, d = 0.926 g cm-3, 2.5187 g, 22.49 mmol)/dioxane (8 mL) for 15 h afforded product (Ra)-4be (1.1104 g ) [(eluent: petroleum ether (60-90 oC)/diethyl ether = 100/1 (500 mL × 3)] as a liquid, which was then submitted to next step. Typical Procedure V: To a round-bottom flask were added (Ra)-4be (1.1104 g, 5.0 mmol, prepared above), EtOH/H2O = 1:1 by volume (pre-mixed by using 25 mL of H2O and 25 mL of EtOH), and LiOH·H2O (0.3321 g, 7.5 mmol, 95%) sequentially. After continuous stirring for 18 h under reflux at 90 oC, the reaction was complete as monitored by TLC. Then the mixture was cooled down to room temperature. After

16

evaporation to remove EtOH, the resulting mixture was extracted with 5 mL of Et2O. The organic layer was separated and the aqueous layer was acidified with an aqueous solution of hydrochloric acid (aq., 3.0 M) until pH = 1. The aqueous layer was then extracted with Et2O (20 mL × 3). The combined organic layer was washed with brine and

dried

over

anhydrous

Na2SO4.

Filtration,

evaporation,

and

column

chromatography on silica gel [(eluent: petroleum ether (60-90 oC)/ethyl acetate = 8/1 (450 mL) to 5/1 (500 mL × 3)] gave impure (Ra)-5e (0.9991) as an oil; then the impure (Ra)-5e was purified again on silica gel [(eluent: petroleum ether (30-60 o

C)/ethyl acetate = 8/1 (270 mL) to 5/1 (500 mL × 2)] to afford pure (Ra)-5e (0.9826 g,

34%, 2 steps) as an oil: 97% ee (determined by the corrsponding esterification product (Ra)-4be); [α]D20 = -91.6 (c = 1.005, CHCl3); 1H NMR (300 MHz, CDCl3) δ 11.18 (bs, 1H, COOH), 5.26-5.11 (m, 2H, =CH × 2), 2.55-2.42 (m, 2H, CH2), 2.36-2.22 (m, 2H, CH2), 2.01-1.86 (m, 1H, CH), 1.81-1.55 (m, 5H, one proton of CH2 + CH2 × 2), 1.35-0.95 (m, 5H, one proton of CH2 + CH2 × 2); 13C NMR (75 MHz, CDCl3) δ 202.4, 180.0, 98.9, 90.1, 37.1, 33.1, 32.9, 26.1, 26.0, 23.5; IR (neat) ν (cm−1) 3624-2266 (COOH), 3032, 2924, 2851, 2659, 1962, 1712, 1448, 1412, 1335, 1288, 1250, 1211, 1175, 1132, 1077; MS (70 ev, EI) m/z (%) 194 (M+, 2.79), 41 (100); HRMS calcd for C12H18O2 [M+]: 194.1307, found: 194.1305.

Esterification for determination of the ee value of (Ra)-5e: synthesis of (Ra)-ethyl 6-cyclohexyl-4,5-hexadienoate (Ra)-4be6 (zj-4-006)

To a reaction tube were added (Ra)-5e (0.0978 g, 0.5 mmol, prapared above), EtOH (0.09 mL, d = 0.789 g cm-3, 0.071g, 1.54 mmol), and DCM (5 mL). Then DCC (0.1160 g, 0.55 mmol, 98%) and DMAP (0.0062 g, 0.05 mmol, 98%) were added sequentially. After continuous stirring at room temperature for 6 h, the reaction was complete as monitored by TLC. After quenching with water (10 mL) with stirring for 10 min, the aqueous solution was extracted with Et2O (10 mL × 3). The combined

17

organic layer was washed with brine and dried over anhydrous Na2SO4. Filtration, evaporation, and column chromatography on silica gel gave (Ra)-4be (0.0933 g, impure) [(eluent: petroleum ether (60-90 oC)/ethyl acetate = 100/1 (800 mL)] as a liquid. The impure (Ra)-4be was diluted with 10 mL of Et2O and then washed with an aqueous solution of hydrochloric acid (aq., 3.0 M) (10 mL × 3) and brine. After drying over anhydrous Na2SO4, filtration, evaporation, and column chromatography on silica gel gave pure (Ra)-4be (0.0817 g, 73%) [(eluent: petroleum ether (60-90 o

C)/ethyl acetate = 100/1 (800 mL)] as a liquid: 97% ee (HPLC conditions: Chiralcel

AY column, n-hexane, 0.6 mL/min, λ = 214 nm, tR (major) = 17.32 min), [α]D20 = -81.9 (c = 0.99, CHCl3); 1H NMR (300 MHz, CDCl3) δ 5.26-5.08 (m, 2H, =CH × 2), 4.13 (q, J = 7.1 Hz, 2H, OCH2), 2.48-2.36 (m, 2H, CH2), 2.35-2.22 (m, 2H, CH2), 2.01-1.84 (m, 1H, CH), 1.81-1.56 (m, 5H, one proton of CH2 + CH2 × 2), 1.36-0.95 (m, 8H, CH3 + one proton of CH2 + CH2 × 2); 13C NMR (75 MHz, CDCl3) δ 202.4, 173.1, 98.5, 90.4, 60.2, 37.1, 33.3, 33.0, 32.9, 26.1, 26.0, 23.8, 14.1; IR (neat) ν (cm−1) 2977, 2925, 2851, 1960, 1738, 1448, 1418, 1372, 1348, 1302, 1290, 1250, 1227, 1195, 1158, 1096, 1037; MS (70 ev, EI) m/z (%) 222 (M+, 6.25), 29 (100); HRMS calcd for C14H22O2 [M+]: 222.1620, found: 222.1618;

7. Synthesis of (Ra)-7-phenyl-4,5-heptadienoic acid (Ra)-5f (zj-4-163, 4-169)

Following Typical Procedure IV, the reaction of CuBr2 (0.6763 g, 3.0 mmol, 99%), (S)-3a (3.8769 g, 15 mmol, 98%), 1b (2.2719 g, 18 mmol)/dioxane (15 mL), and phenylacetaldehyde 2f (2.69 mL, d = 1.025 g cm-3, 2.7021 g, 22.52 mmol, 98%)/dioxane (10 mL) for 17 h afforded (Ra)-4bf (1.3907 g) [(eluent: petroleum ether (60-90 oC)/diethyl ether = 100/1 (500 mL × 2) to 50/1 (500 mL × 2)] as a liquid, which was then submitted to next step. Following Typical Procedure V, the reaction of (Ra)-4bf (1.3907 g, 6.0 mmol,

18

prepared above), EtOH/H2O = 1:1 by volume (pre-mixed by using 30 mL of H2O and 30 mL of EtOH), and LiOH·H2O (0.4017 g, 9.0 mmol, 95%) for 12 h afforded (Ra)-5f (1.0324 g, 34%, 2 steps) [(eluent: petroleum ether (60-90 oC)/ethyl acetate = 20/1 (420 mL) to 10/1 (500 mL × 2)] as an oil: 96% ee (determined by the corrsponding esterification product (Ra)-4bf); [α]D20 = -79.7 (c = 1.005, CHCl3); 1H NMR (300 MHz, CDCl3) δ 10.53 (bs, 1H, COOH), 7.33-7.24 (m, 2H, ArH), 7.24-7.11 (m, 3H, ArH), 5.39-5.26 (m, 1H, =CH), 5.25-5.12 (m, 1H, =CH), 3.31 (dd, J1 = 6.9 Hz, J2 = 2.7 Hz, 2H, CH2), 2.46-2.37 (m, 2H, CH2), 2.34-2.21 (m, 2H, CH2);

13

C NMR (75

MHz, CDCl3) δ 204.2, 179.7, 140.1, 128.4, 128.3, 126.1, 92.2, 89.9, 35.5, 33.0, 23.4; IR (neat) ν (cm−1) 3600-2197 (COOH), 3084, 3060, 3028, 2980, 2915, 2665, 1964, 1712, 1603, 1494, 1453, 1428, 1334, 1279, 1251, 1212, 1173, 1075, 1029; MS (70 ev, EI) m/z (%) 202 (M+, 4.51), 143 (100), 142 (100), 129 (100), 128 (100), 91 (100); HRMS calcd for C13H14O2 [M+]: 202.0994, found: 202.0997.

Esterification for determination of the ee value of (Ra)-5f: synthesis of (Ra)-ethyl 7-phenyl-4,5-heptadienoate (Ra)-4bf (zj-4-174)

Following Typical Procedure III, the reaction of (Ra)-5f (0.1017 g, 0.5 mmol)/DMF (5 mL), EtI (0.05 mL, d = 1.94 g cm-3, 0.096 g, 0.616 mmol, 99%), and K2CO3 (0.2075 g, 1.5 mmol) for 11 h afforded (Ra)-4bf (0.1066 g, 92%) [eluent: petroleum ether (60-90 oC)/ethyl acetate = 100/1 (500 mL)] as a liquid: 96% ee (HPLC conditions: Chiralcel AS-H column, n-hexane, 1.0 mL/min, λ = 214 nm, tR (major) = 20.3 min, tR (minor) = 23.3 min); [α]D20 = -75.3 (c = 1.00, CHCl3); 1H NMR (300 MHz, CDCl3) δ 7.33-7.24 (m, 2H, ArH), 7.24-7.13 (m, 3H, ArH), 5.35-5.24 (m, 1H, =CH), 5.24-5.13 (m, 1H, =CH), 4.10 (q, J = 7.2 Hz, 2H, OCH2), 3.31 (dd, J1 = 7.1 Hz, J2 = 2.9 Hz, 2H, CH2), 2.42-2.22 (m, 4H, CH2 × 2), 1.23 (t, J = 7.2 Hz, 3H, CH3);

13

C NMR (75 MHz, CDCl3) δ 204.2, 172.9, 140.1, 128.3, 128.2, 126.0, 91.7,

90.2, 60.1, 35.5, 33.2, 23.7, 14.1; IR (neat) ν (cm−1) 3084, 3060, 3027, 2980, 2908,

19

2871, 2848, 1963, 1735, 1603, 1494, 1453, 1420, 1372, 1350, 1301, 1251, 1159, 1096, 1054, 1030; MS (70 ev, EI) m/z (%) 230 (M+, 10.54), 91 (100); HRMS calcd for C15H18O2 [M+]: 230.1307, found: 230.1311.

8. Synthesis of (Ra)-8-phenyl-4,5-octadienoic acid (Ra)-5g (zj-4-136, 4-139)

Following Typical Procedure IV, the reaction of CuBr2 (0.6764 g, 3.0 mmol, 99%), (S)-3a (3.8655 g, 15 mmol, 98%), 1b (2.2671 g, 18 mmol)/dioxane (15 mL), and phenylpropyl aldehyde 2g (3.0 mL, d = 1.015 g cm-3, 3.045 g, 22.7 mmol)/dioxane (10 mL) for 17.5 h afforded (Ra)-4bg (1.8685 g) [(eluent: petroleum ether (60-90 oC)/diethyl ether = 100/1 (500 mL × 3) to 50/1 (500 mL × 2)] as a liquid, which was then submitted to next step. Following Typical Procedure V, the reaction of (Ra)-4bg (1.8685 g, 7.66 mmol, prepared above), EtOH/H2O = 1:1 by volume (pre-mixed by using 30 mL of H2O and 30 mL of EtOH), and LiOH·H2O (0.5082 g, 11.5 mmol, 95%) for 18 h afforded (Ra)-5g (1.4516 g, 45%, 2 steps) [(eluent: petroleum ether (60-90 oC)/ethyl acetate = 20/1 (220 mL) to 10/1 (500 mL) to 5/1 (500 mL × 2)] as an oil: 96% ee (determined by the corrsponding esterification product (Ra)-4bg); [α]D20 = -71.8 (c = 1.005, CHCl3); 1H NMR (300 MHz, CDCl3) δ 11.15 (bs, 1H, COOH), 7.32-7.23 (m, 2H, ArH), 7.23-7.13 (m, 3H, ArH), 5.27-5.10 (m, 2H, =CH × 2), 2.76-2.65 (m, 2H, CH2), 2.42-2.15 (m, 6H, CH2 × 3); 13C NMR (75 MHz, CDCl3) δ 203.8, 179.7, 141.7, 128.5, 128.2, 125.8, 92.1, 89.8, 35.2, 32.9, 30.4, 23.3; IR (neat) ν (cm−1) 3696-2194 (COOH), 3087, 3062, 3027, 2974, 2920, 2856, 2660, 1963, 1713, 1603, 1496, 1454, 1435, 1411, 1336, 1278, 1250, 1211, 1175, 1133, 1078, 1030; MS (70 ev, EI) m/z (%) 216 (M+, 4.92), 129 (100), 91 (100); HRMS calcd for C14H16O2 [M+]: 216.1150, found: 216.1154.

20

Esterification for determination of the ee value of (Ra)-5g: synthesis of (Ra)-ethyl 8-phenyl-4,5-octadienoate (Ra)-4bg (zj-4-141)

Following Typical Procedure III, the reaction of (Ra)-5g (0.1081 g, 0.5 mmol)/DMF (5 mL), EtI (0.05 mL, d = 1.94 g cm-3, 0.096 g, 0.616 mmol, 99%), and K2CO3 (0.2079 g, 1.5 mmol) for 11 h afforded (Ra)-4bg (0.1177 g, 96%) [eluent: petroleum ether (60-90 oC)/ethyl acetate = 100/1 (800 mL)] as a liquid: 96% ee (HPLC conditions: Chiralcel AS-H column, n-hexane, 0.7 mL/min, λ = 214 nm, tR (major) = 18.5 min, tR (minor) = 22.8 min); [α]D20 = -71.3 (c = 1.00, CHCl3); 1H NMR (300 MHz, CDCl3) δ 7.31-7.22 (m, 2H, ArH), 7.22-7.09 (m, 3H, ArH), 5.26-5.09 (m, 2H, =CH × 2), 4.12 (q, J = 7.3 Hz, 2H, OCH2), 2.70 (t, J = 7.7 Hz, 2H, CH2), 2.39-2.18 (m, 6H, CH2 × 3), 1.25 (t, J = 7.2 Hz, 3H, CH3); 13C NMR (75 MHz, CDCl3) δ 203.8, 173.0, 141.6, 128.4, 128.2, 125.8, 91.7, 90.1, 60.2, 35.2, 33.3, 30.4, 23.7, 14.2; IR (neat) ν (cm−1) 3085, 3062, 3027, 2979, 2924, 2855, 1963, 1737, 1603, 1496, 1454, 1372, 1349, 1300, 1250, 1196, 1158, 1133, 1096, 1077, 1030; MS (70 ev, EI) m/z (%) 244 (M+, 3.56), 129 (100), 91 (100); HRMS calcd for C16H20O2 [M+]: 244.1463, found: 244.1470.

9. Synthesis of (Ra)-4,5,15-hexadecatrienoic acid (Ra)-5h (zj-5-035, 5-056)

Following Typical Procedure IV, the reaction of CuBr2 (0.6760 g, 3.0 mmol, 99%), (S)-3a (3.8667 g, 15 mmol, 98%), 1b (2.2702 g, 18 mmol)/dioxane (15 mL), and 10-undecylenealdehyde 2h (4.6 mL, d = 0.84 g cm-3, 3.7867 g, 22.54 mmol, 98%)/dioxane (10 mL) for 19 h afforded (Ra)-4bh (2.6107 g) [(eluent: petroleum ether (60-90 oC)/diethyl ether = 100/1 (500 mL × 3) to 50/1 (500 mL)] as a liquid, which

21

was then submitted to next step. Following Typical Procedure V, the reaction of (Ra)-4bh (2.6107 g, 9.4 mmol, prepared above), EtOH/H2O = 1:1 by volume (pre-mixed by using 30 mL of H2O and 30 mL of EtOH), and LiOH·H2O (0.6235 g, 14.1 mmol, 95%) for 18 h afforded (Ra)-5h4 (1.5036 g, 40%, 2 steps) [(eluent: petroleum ether (60-90 oC)/ethyl acetate = 10/1 (600 mL) to 5/1 (540 mL)] as an oil: 96% ee (determined by the corrsponding esterification product (Ra)-4bh); [α]D20 = -60.3 (c = 1.015, CHCl3); 1H NMR (300 MHz, CDCl3) δ 10.56 (bs, 1H, COOH), 5.89-5.70 (m, 1H, =CH), 5.25-5.09 (m, 2H, 2 × =CH), 5.05-4.86 (m, 2H, =CH2), 2.56-2.42 (m, 2H, CH2), 2.36-2.23 (m, 2H, CH2), 2.11-1.90 (m, 4H, 2 × CH2), 1.44-1.20 (m, 12H, 6 × CH2); 13C NMR (75 MHz, CDCl3) δ 203.7, 179.8, 139.2, 114.1, 92.8, 89.2, 33.8, 33.1, 29.43, 29.37, 29.09, 29.07, 28.89, 28.81, 23.48; IR (neat) ν (cm−1) 3672-2224 (COOH), 3075, 2977, 2925, 2854, 2664, 1964, 1711, 1640, 1436, 1411, 1337, 1280, 1249, 1211, 1172; MS (70 ev, EI) m/z (%) 251 (M+ + 1, 2.66), 250 (M+, 3.26), 126 (100), 81 (100).

Esterification for determination of the ee value of (Ra)-5h: synthesis of (Ra)-ethyl -4,5,15-hexadecatrienoate (Ra)-4bh (zj-5-065)

Following Typical Procedure III, the reaction of (Ra)-5h (0.1020 g, 0.4 mmol)/DMF (4 mL), EtI (0.04 mL, d = 1.94 g cm-3, 0.076 g, 0.49 mmol, 98%), and K2CO3 (0.1673 g, 1.2 mmol) for 17 h afforded (Ra)-4bh (0.1100 g, 97%) [eluent: petroleum ether (60-90 oC)/ethyl acetate = 100/1 (700 mL)] as a liquid: 96% ee (HPLC conditions: Chiralcel OZ-H column, n-hexane, 0.5 mL/min, λ = 214 nm, tR (major) = 22.0 min, tR (minor) = 21.0 min); [α]D20 = -53.9 (c = 0.995, CHCl3); 1H NMR (300 MHz, CDCl3) δ 5.86-5.72 (m, 1H, =CH), 5.18-5.06 (m, 2H, 2 × =CH), 5.04-4.87 (m, 2H, =CH2), 4.12 (q, J = 7.1 Hz, 2H, OCH2), 2.45-2.36 (m, 2H, CH2), 2.34-2.22 (m, 2H, CH2), 2.09-1.90 (m, 4H, 2 × CH2), 1.44-1.19 (m, 15H, 6 × CH2 +

22

CH3); 13C NMR (75 MHz, CDCl3) δ 203.6, 172.9, 139.0, 114.0, 92.3, 89.4, 60.1, 33.7, 33.3, 29.32, 29.28, 29.0, 28.8, 28.7, 23.8, 14.1; IR (neat) ν (cm−1) 3076, 2978, 2926, 2854, 1962, 1738, 1640, 1462, 1444, 1371, 1348, 1299, 1249, 1159, 1096, 1037; MS (70 ev, EI) m/z (%) 278 (M+, 20.44), 279 (M+ + 1, 6.16), 154 (100); HRMS calcd for C18H30O2 [M+]: 278.2246, found: 278.2249.

10. Synthesis of (Ra)-14-(tert-butyldimethylsilyl)-4,5-tetradecadien-13-ynoic acid (Ra)-5i (zj-6-184, 6-186)

Following Typical Procedure IV, the reaction of CuBr2 (0.3155 g, 1.4 mmol, 99%), (S)-3a (1.8071 g, 7 mmol, 98%), 1b (1.0575 g, 8.4 mmol)/dioxane (25 mL), and aldehyde 2i7 (2.6397 g, 10.5 mmol; TBS: tert-butyldimethylsilyl)/dioxane (10 mL) for 18 h afforded (Ra)-4bi (1.2865 g) [(eluent: petroleum ether (60-90 oC)/diethyl ether = 100/1 (500 mL × 2) to 50/1 (500 mL) to 30/1 (600 mL)] as a liquid, which was then submitted to next step. To a round-bottom flask were added (Ra)-4bi (1.2865 g, 3.55 mmol, prepared above), THF/MeOH/H2O = 1:1:1 by volume (pre-mixed by using 6.5 mL of THF, 6.5 mL of MeOH and 6.5 mL of H2O), and LiOH·H2O (0.1571 g, 3.55 mmol, 95%) sequentially. After continuous stirring for 5 h at room temperature, the reaction was complete as monitored by TLC.8 Then MeOH and THF were removed via evaporation, the resulting mixture was acidified with an aqueous solution of hydrochloric acid (aq., 1.0 M) until pH = 1. The aqueous layer was then extracted with Et2O (25 mL × 3). After being washed with brine and dried over anhydrous Na2SO4, filtration, evaporation, and column chromatography on silica gel gave (Ra)-5i (0.9826 g, 42%, 2 steps) [(eluent: petroleum ether (60-90 oC)/ethyl acetate = 15/1 (480 mL) to 10/1 (550 mL) to 8/1 (540 mL)] as an oil: 97% ee (determined by the corrsponding esterification

23

product (Ra)-4bi); [α]D20 = -48.7 (c = 1.025, CHCl3); 1H NMR (300 MHz, CDCl3) δ 10.92 (bs, 1H, COOH), 5.24-5.03 (m, 2H, =CH × 2), 2.45 (t, J = 7.4 Hz, 2H, CH2), 2.36-2.24 (m, 2H, CH2), 2.20 (t, J = 7.1 Hz, 2H, CH2), 2.01-1.89 (m, 2H, CH2), 1.57-1.24 (m, 8H, CH2 × 4), 0.91 (s, 9H, CH3 × 3), 0.06 (s, 6H, CH3 × 2); 13C NMR (75 MHz, CDCl3) δ 203.7, 179.8, 108.1, 92.7, 89.3, 82.3, 33.1, 28.9, 28.7, 28.6, 28.5, 26.0, 23.4, 19.7, 16.4, -4.50; IR (neat) ν (cm−1) 3685-2304 (COOH), 2929, 2856, 2660, 2172, 1964, 1711, 1463, 1432, 1413, 1360, 1332, 1251, 1211, 1167, 1009; MS (70 ev, EI) m/z (%) 335 (M+ + 1, 11.48), 334 (M+, 6.86), 75 (100); HRMS calcd for C20H34O2Si [M+]: 334.2328, found: 334.2332.

Esterification for determination of the ee value of (Ra)-5i: synthesis of (Ra)-ethyl 14-(tert-butyldimethylsilyl)-4,5-tetradecadien-13-ynoate (Ra)-4bi (zj-6-191)

Following Typical Procedure III, the reaction of (R)-5i (0.1002 g, 0.3 mmol)/DMF (3 mL), EtI (0.03 mL, d = 1.94 g cm-3, 0.057 g, 0.366 mmol, 98%), and K2CO3 (0.1242 g, 0.9 mmol) for 11 h afforded (R)-4bi (0.1035 g, 96%) [eluent: petroleum ether (60-90 oC)/ethyl acetate = 100/1 (300 mL) to 50/1 (400 mL)] as a liquid: 97% ee (HPLC conditions: Chiralcel OZ-H column, n-hexane, 1.0 mL/min, λ = 214 nm, tR (major) = 30.5 min, tR (minor) = 29.1 min); [α]D20 = -45.3 (c = 1.00, CHCl3); 1H NMR (300 MHz, CDCl3) δ 5.19-5.00 (m, 2H, =CH × 2), 4.10 (q, J = 7.2 Hz, 2H, OCH2), 2.44-2.32 (m, 2H, CH2), 2.32-2.22 (m, 2H, CH2), 2.19 (t, J = 6.9 Hz, 2H, CH2), 2.01-1.86 (m, 2H, CH2), 1.54-1.26 (m, 8H, CH2 × 4), 1.22 (t, J = 7.1 Hz, 3H, CH3), 0.89 (s, 9H, CH3 × 3), 0.04 (s, 6H, CH3 × 2); 13C NMR (75 MHz, CDCl3) δ 203.6, 173.0, 108.0, 92.3, 89.5, 60.2, 33.4, 28.9, 28.7, 28.6, 28.5, 26.0, 23.8, 19.7, 16.4, 14.2, -4.5; IR (neat) ν (cm−1) 2931, 2857, 2172, 1963, 1738, 1464, 1370, 1299, 1251, 1159, 1097, 1034; MS (70 ev, EI) m/z (%) 363 (M+ + 1, 27.35), 362 (M+, 16.06), 231 (100); HRMS calcd for C22H38O2Si [M+]: 362.2641, found: 362.2646.

24

11. Esterification for determination of the ee value of (Sa)-5m: synthesis of (Sa)-ethyl 4,5-dodecadienoate (Sa)-4bm (zj-9-055)

Following Typical Procedure III, the reaction of (Sa)-5m4 (0.0982 g, 0.5 mmol)/DMF (5 mL), EtI (0.05 mL, d = 1.94 g cm-3, 0.097 g, 0.62 mmol, 99%), and K2CO3 (0.2073 g, 1.5 mmol) for 12 h afforded (Sa)-4bm (0.1091 g, 97%) [eluent: petroleum ether (60-90 oC)/ethyl acetate = 50/1 (450 mL)] as a liquid: 97% ee (HPLC conditions: Chiralcel OD-H column, n-hexane, 1.0 mL/min, λ = 214 nm, tR (major) = 15.2 min, tR (minor) = 17.1 min); [α]D20 = +63.9 (c = 1.00, CHCl3); 1H NMR (300 MHz, CDCl3) δ 5.23-5.07 (m, 2H, =CH × 2), 4.13 (q, J = 7.2 Hz, 2H, OCH2), 2.46-2.37 (m, 2H, CH2), 2.36-2.23 (m, 2H, CH2), 2.06-1.91 (m, 2H, CH2), 1.44-1.19 (m, 11H, CH2 × 4 + CH3), 0.89 (t, J = 6.8 Hz, 3H, CH3); 13C NMR (75 MHz, CDCl3) δ 203.6, 173.0, 92.4, 89.4, 60.1, 33.3, 31.6, 29.0, 28.8, 28.7, 23.8, 22.5, 14.1, 14.0; IR (neat) ν (cm−1) 2957, 2927, 2856, 1963, 1738, 1465, 1446, 1372, 1350, 1300, 1251, 1196, 1180, 1159, 1097, 1076, 1039; MS (70 ev, EI) m/z (%) 224 (M+, 5.38), 80 (100); HRMS calcd for C14H24O2 [M+]: 224.1776, found: 224.1782.

Synthesis of AuCl(LB-Phos)9 (zj-7-180)

To a three-neck flask were added NaAuCl4∙2H2O (0.5230 g, 1.3 mmol, 99%) and H2O (20 mL). The solution was cooled to 0 °C by an ice bath, and S(CH2CH2OH)2 (0.4759 g, 3.9 mmol,) in H2O (5 mL) was added within 20 min. After the addition was

25

complete, the reaction mixture was stirred for 40 min at 0 oC. Then a solution of LB-Phos (0.4737 g, 1.3 mmol) in DCM (5 mL) was added dropwise at 0 °C within 20 min. Then the reaction was warmed up to room temperature. After stirring for 30 min, the reaction was complete as monitored by TLC. The reaction mixture was extracted with DCM (20 mL × 4). The combined organic layer was washed with brine and dried over anhydrous Na2SO4. After filtration and evaporation, the residue was purified by chromatography [eluent: petroleum ether (60-90 oC)/ethyl acetate = 5/1 (600 mL) to 3/1 (600 mL) to 2/1 (600 mL)] on silica gel to afford AuCl(LB-Phos) (0.3971 g, 51%) as a white solid, which is stable in air and H2O: m. p. 217.5-218.7 oC (diethyl ether/dichloromethane); 1H NMR (300 MHz, CDCl3) δ 6.14 (d, 2H, J = 3.0 Hz, ArH), 3.87 (s, 3H, CH3), 3.84 (s, 6H, CH3 × 2), 2.53-2.37 (m, 2H, CH2), 2.12-1.99 (m, 2H, CH2), 1.88-1.45 (m, 10H, CH2 × 5), 1.41-1.09 (m, 8H, CH2 × 4); 13C NMR (75 MHz, CDCl3) δ 164.5, 163.9, 92.7 (d, J = 55.2 Hz), 91.3 (d, J = 4.9 Hz), 55.44, 55.36, 35.8 (d, J = 35.9 Hz), 32.2 (d, J = 5.5 Hz), 29.3, 26.7 (d, J = 13.1 Hz), 26.4 (d, J = 15.8 Hz), 25.6; 31P NMR (121 MHz, CDCl3) δ 31.3; IR (neat) ν (cm−1) 3042, 3002, 2927, 2850, 1597, 1459, 1408, 1334, 1291, 1267, 1228, 1207, 1181, 1161, 1123, 1092, 1029, 1003; MS (70 ev, EI) m/z (%) 598 (M+ + 1, 18.14), 597 (M+, 12.34), 478 (100); Elemental analysis calcd (%) for C21H33AuClO3P: C, 42.26; H, 5.57; Found: C, 42.18; H, 5.74. Crystal data for AuCl(LB-Phos): C21H33AuClO3P, MW = 596.86, orthorhombic, space group P 21 21 21, final R indices [I > 2\s (I)], R1 = 0.0321, wR2 = 0.0701, R indices (all data) R1 = 0.0365, wR2 = 0.0667, a = 11.6086 (6) Å, b = 13.0711 (8) Å, c = 15.0247 (10) Å, α = 90o, β = 90o, γ = 90o, V = 2279.8 (2) Å3, T = 170 K, Z = 4, reflections collected/unique: 14515/4141 (Rint = 0.0544), number of observations [> 2\s (I)] 3869, parameters: 247. CCDC 1558142.

Highly stereoselective synthesis of (S,E)-6 1. Synthesis of (S,E)-5-(1-nonenyl)dihydro-2(3H)-furanone (S,E)-6a (zj-8-046)

26

Typical Procedure VI: To a dry Schlenk tube were added AgOTs (0.0142 g, 0.05 mmol, weighed in glove box, 98%), AuCl(LB-Phos) (0.0299 g, 0.05 mmol), and CHCl3 (5 mL) under nitrogen atmosphere sequentially. After stirring for 15 min, (R)-trideca-4,5-allenoic acid (Ra)-5a and CHCl3 (5 mL) were added. After being continuously stirred at 25 oC for 3 h, the reaction was complete as monitored by TLC. Filtration through a short column of silica gel [eluent: Et2O (20 mL × 3)] and evaporation afforded a crude mixture of (S,E)-6a and (R,Z)-6a ((S,E)/(R,Z) = 97/3, as determined by 1H NMR analysis). Column chromatography on silica gel afforded (S,E)-6a (0.2017 g, 96%, (S,E)/(R,Z) = 98/2 as determined by 1H NMR analysis) [eluent: petroleum ether (60-90 oC)/ethyl acetate = 15/1 (400 mL) to 10/1 (550 mL)] as an oil with pleasant flavor: 96% ee (HPLC conditions: Chiralcel OJ-H column, n-hexane/i-PrOH = 200/1, 1.0 mL/min, λ = 214 nm, tR (major) = 22.73 min, tR (minor) = 20.86 min); [α]D20 = +29.6 (c = 1.01, CHCl3); 1H NMR (300 MHz, CDCl3) δ 5.81 (dt, J1 = 15.3 Hz, J2 = 7.2 Hz, 1H, =CH), 5.49 (dd, J1 = 15.3 Hz, J2 = 7.2 Hz, 1H, =CH), 4.90 (q, J = 7.2 Hz, 1H, CH), 2.61-2.50 (m, 2H, CH2), 2.46-2.31 (m, 1H, one proton from CH2), 2.13-1.90 (m, 3H, CH2 + one proton from CH2), 1.45-1.18 (m, 10H, CH2 × 5), 0.88 (t, J = 6.6 Hz, 3H, CH3); the following signals are discernible for (R,Z)-6a: δ 5.72-5.62 (m, 1H, =CH), 5.31-5.21 (m, 1H, CH);

13

C NMR (75 MHz,

CDCl3) δ 177.0, 135.6, 127.2, 81.1, 32.0, 31.6, 29.0, 28.9, 28.7, 28.64, 28.61, 22.5, 14.0; IR (neat) ν (cm−1) 2955, 2926, 2855, 1778, 1673, 1459, 1415, 1378, 1327, 1296, 1216, 1177, 1123, 1010; GC-MS (GC condition: injector: 280 oC; column: DB5 column 30 m × 0.25 mm, temperature programming: 60 oC (2 min), 20 oC/min to 280 o

C, 280 oC (30 min); detector: 280 oC) (70 ev, EI) m/z (%) for (S,E)-6a: tR (major) =

5.83 min: 210 (M+, 2.31), 111 (100); for (R,Z)-6a: tR (minor) = 5.76 min: 210 (M+, 0.75), 111 (100). HRMS calcd for C13H22O2 [M+]: 210.1620, found: 210.1624.

2. Synthesis of (S,E)-5-(1-hexenyl)dihydro-2(3H)-furanone (S,E)-6b (zj-6-074)

27

Following Typical Procedure VI, the reaction of AgOTs (0.0142 g, 0.05 mmol, 98%), Au(LB-Phos)Cl (0.0299 g, 0.05 mmol), CHCl3 (5 mL), and (Ra)-5b (0.1680 g, 1.0 mmol)/CHCl3 (5 mL) for 3.0 h afforded (S,E)-6b10 (0.1563 g, 93%, (S,E)/(R,Z) = 97/3 determined by 1H NMR) [eluent: petroleum ether (60-90 oC)/ethyl acetate = 10/1 (550 mL) to 8/1 (540 mL)] ((S,E)/(R,Z) = 96/4 determined by 1H NMR of crude product) as a liquid with pleasant flavor: 96% ee (HPLC conditions: Chiralcel OJ-H column, n-hexane/i-PrOH = 200/1, 1.0 mL/min, λ = 214 nm, tR (major) = 29.0 min, tR (minor) = 26.3 min); [α]D20 = +36.3 (c = 1.02, CHCl3); 1H NMR (300 MHz, CDCl3) δ 5.81 (dtd, J1 = 15.3 Hz, J2 = 7.2 Hz, J3 = 0.9 Hz, 1H, =CH), 5.50 (ddt, J1 = 15.5 Hz, J2 = 7.1 Hz, J3 = 1.4 Hz, 1H, =CH), 4.90 (q, J = 7.1 Hz, 1H, CH), 2.60-2.49 (m, 2H, CH2), 2.46-2.31 (m, 1H, one proton from CH2), 2.12-1.90 (m, 3H, CH2 + one proton from CH2), 1.45-1.24 (m, 4H, CH2 × 2), 0.90 (t, J = 7.1 Hz, 3H, CH3); the following signals are discernible for (R,Z)-6b: δ 5.72-5.62 (m, 1H, =CH), 5.31-5.21 (m, 1H, CH); 13C NMR (75 MHz, CDCl3) δ 176.9, 142.0, 124.4, 81.0, 30.4, 28.6, 28.5, 21. 6; IR (neat) ν (cm−1) 2957, 2929, 2872, 2859, 1778, 1673, 1460, 1423, 1379, 1328, 1295, 1217, 1178, 1123, 1054, 1006; GC-MS (GC condition: injector: 280 oC; column: DB5 column 30 m × 0.25 mm, temperature programming: 60 oC (2 min), 20 oC/min to 280 o

C, 280 oC (30 min); detector: 280 oC) (70 ev, EI) m/z (%) for (S,E)-6b: tR (major) =

4.47 min: 168 (M+, 1.61), 111 (100); for (R,Z)-6b tR (minor) = 4.42 min: 168 (M+, 1.83), 111 (100).

3. Synthesis of (S,E)-5-(1-tridecenyl)dihydro-2(3H)-furanone (S,E)-6c (zj-4-114)

Following Typical Procedure VI, the reaction of AgOTs (0.0143 g, 0.05 mmol, 98%), Au(LB-Phos)Cl (0.0300 g, 0.05 mmol), CHCl3 (5 mL), and (Ra)-5c (0.2663 g,

28

1.0 mmol)/CHCl3 (5 mL) for 2.5 h afforded (S,E)-6c (0.2604 g, 98%, (S,E)/(R,Z) = 98/2 determined by 1H NMR) [eluent: petroleum ether (30-60 oC)/ethyl acetate = 20/1 (300 mL) to 10/1 (500 mL)] ((S,E)/(R,Z) = 97/3 determined by 1H NMR of crude product) as an oil with pleasant flavor: 96% ee (HPLC conditions: Chiralcel AS-H column, n-hexane/i-PrOH = 95:5, 1.0 mL/min, λ = 214 nm, tR (major) = 7.3 min, tR (minor) = 6.7 min; [α]D20 = +23.0 (c = 1.005, CHCl3); 1H NMR (300 MHz, CDCl3) δ 5.81 (dt, J1 = 15.3 Hz, J2 = 7.1 Hz, 1H, =CH), 5.49 (dd, J1 = 15.5 Hz, J2 = 7.1 Hz, 1H, =CH), 4.89 (q, J = 7.2 Hz, 1H, CH), 2.59-2.49 (m, 2H, CH2), 2.44-2.31 (m, 1H, one proton from CH2), 2.13-1.89 (m, 3H, one proton from CH2 + CH2), 1.46-1.20 (m, 18H, CH2 × 8), 0.88 (t, J = 6.6 Hz, 3H, CH3); the following signals are discernible for (R,Z)-6c: δ 5.72-5.62 (m, 1H, =CH), 5.30-5.20 (m, 1H, CH);

13

C NMR (75 MHz,

CDCl3) δ 177.0, 135.6, 127.2, 81.1, 32.0, 31.8, 29.53, 29.51, 29.45, 29.3, 29.2, 29.0, 28.73, 28.66, 28.6, 22.6, 14.0; IR (neat) ν (cm−1) 2925, 2854, 1779, 1672, 1461, 1422, 1378, 1327, 1300, 1216, 1176, 1123, 1010; GC-MS (GC condition: injector: 280 oC; column: DB5 column 30 m × 0.25 mm, temperature programming: 60 oC (2 min), 20 o

C/min to 280 oC, 280 oC (30 min); detector: 280 oC) (70 ev, EI) m/z (%) for (S,E)-6c:

tR (major) = 4.9 min: 266 (M+, 1.24), 111 (100); for (R,Z)-6c tR (minor) = 4.8 min): 266 (M+, 2.32), 111 (100). HRMS calcd for C17H30O2 [M+]: 266.2246, found: 266.2250.

4.

Synthesis

of

(S,E)-5-(3-methyl-1-butenyl)dihydro-2(3H)-furanone

(S,E)-6d

(zj-8-058)

Following Typical Procedure VI, the reaction of AgOTs (0.0142 g, 0.05 mmol, 98%), Au(LB-Phos)Cl (0.0300 g, 0.05 mmol), CHCl3 (5 mL), and (Ra)-5d (0.1541 g, 1.0 mmol)/CHCl3 (5 mL) for 3.0 h afforded (S,E)-6d (0.1449 g, 94%, (S,E)/(R,Z) = 99/1 determined by quantitative

13

C NMR analysis) [eluent: petroleum ether (60-90

29

o

C)/ethyl acetate = 15/1 (450 mL) to 10/1 (550 mL)] as a liquid with pleasant flavor:

98% ee (HPLC conditions: Chiralcel AS-H column, n-hexane/i-PrOH = 98/2, 1.0 mL/min, λ = 214 nm, tR (major) = 23.6 min, tR (minor) = 21.3 min); [α]D20 = +37.8 (c = 1.03, CHCl3); 1H NMR (300 MHz, CDCl3) δ 5.79 (ddd, J1 = 15.5 Hz, J2 = 6.5 Hz, J3 = 0.9 Hz, 1H, =CH), 5.50 (ddd, J1 = 15.6 Hz, J2 = 7.2 Hz, J3 = 1.4 Hz, 1H, =CH), 4.90 (q, J = 7.2 Hz, 1H, CH), 2.62-2.50 (m, 2H, CH2), 2.47-2.25 (m, 2H, CH + one proton from CH2), 2.07-1.91 (m, 1H, one proton from CH2), 1.01 (d, J = 6.9 Hz, 6H, CH3 × 2);

13

C NMR (75 MHz, CDCl3) δ 176.9, 142.0, 124.4, 81.0, 30.4, 28.6, 28.5,

21.6; IR (neat) ν (cm−1) 2960, 2927, 2870, 1777, 1463, 1421, 1381, 1327, 1296, 1217, 1176, 1132, 1077, 1012; GC-MS (GC condition: injector: 280 oC; column: DB5 column 30 m × 0.25 mm, temperature programming: 60 oC (2 min), 20 oC/min to 280 o

C, 280 oC (30 min); detector: 280 oC) (70 ev, EI) m/z (%) for (S,E)-6d: tR (major) =

4.06 min: 154 (M+, 6.86), 111 (100); for (R,Z)-6d tR (minor) = 3.95 min: 154 (M+, 14.95), 111 (100); HRMS calcd for C9H14O2 [M+]: 154.0994, found: 154.0996.

5.

Synthesis

of

(S,E)-5-(2-cyclohexylvinyl)dihydro-2(3H)-furanone

(S,E)-6e

(zj-4-008)

Following Typical Procedure VI, the reaction of AgOTs (0.0142 g, 0.05 mmol), Au(LB-Phos)Cl (0.0299 g, 0.05 mmol), CHCl3 (5 mL), and (Ra)-5e (0.1938 g, 1.0 mmol)/CHCl3 (5 mL) for 3 h afforded (S,E)-6e (0.1867 g, 96%, (S,E)/(R,Z) = 99/1 determined by quantitative

13

C NMR analysis) [eluent: petroleum ether (30-60

o

C)/ethyl acetate = 8/1 (500 mL)] as an oil with pleasant flavor: 96% ee (HPLC

conditions: Chiralcel OJ-H column, n-hexane/i-PrOH = 95:5, 1.0 mL/min, λ = 214 nm, tR (major) = 17.1 min, tR (minor) = 13.2 min; [α]D20 = +29.9 (c = 1.005, CHCl3); 1H NMR (300 MHz, CDCl3) δ 5.75 (ddd, J1 = 15.3 Hz, J2 = 6.6 Hz, J3 = 0.75 Hz, 1H,

30

=CH), 5.44 (ddd, J1 = 15.6 Hz, J2 = 7.2 Hz, J3 = 1.2 Hz, 1H, =CH), 4.89 (q, J = 7.1 Hz, 1H, CH), 2.60-2.46 (m, 2H, CH2), 2.46-2.31 (m, 1H, CH), 2.06-1.90 (m, 2H, CH2), 1.79-1.58 (m, 5H, one proton from CH2 + CH2 × 2), 1.36-0.98 (m, 5H, one proton from CH2 + CH2 × 2); 13C NMR (75 MHz, CDCl3) δ 176.6, 140.3, 124.7, 80.8, 39.6, 31.89, 31.85, 28.3, 28.2, 25.5, 25.3; IR (neat) ν (cm−1) 2924, 2851, 1776, 1669, 1449, 1421, 1327, 1291, 1216, 1177, 1126, 1010; GC-MS (GC condition: injector: 280 oC; column: DB5 column 30 m × 0.25 mm, temperature programming: 60 oC (2 min), 20 oC/min to 280 oC, 280 oC (30 min); detector: 280 oC) (70 ev, EI) m/z (%) for (S,E)-6e: tR (major) = 5.22 min: 194 (M+, 5.91), 94 (100); for (R,Z)-6e tR (minor) = 5.08 min): 194 (M+, 11.78), 94 (100). HRMS calcd for C12H18O2 [M+]: 194.1307, found: 194.1307.

6.

Synthesis

of

(S,E)-5-(3-phenyl-1-propenyl)dihydro-2(3H)-furanone

(S,E)-6f

(zj-4-175)

To a dry Schlenk tube were added AgOTs (0.0142 g, 0.05 mmol, weighed in a glove box, 98%), Au(LB-Phos)Cl (0.0299 g, 0.05 mmol), and CHCl3 (5 mL) under nitrogen atmosphere sequentially. After being stirred at room temperature for 15 min, the resulting mixture was cooled down to -40 oC and then (Ra)-5f (0.2021 g, 1.0 mmol) and CHCl3 (5 mL) were added. After being continuously stirred at -40 oC for 6 h, the reaction was complete as monitored by TLC. The resulting mixture was warmed up to room temperature. Filtration through a short column of silica gel [eluent: Et2O (20 mL × 3) at -30oC] and evaporation afforded a crude mixture of (S,E)-6f and (R,Z)-6f ((S,E)/(R,Z) = 97/3, as determined by 1H NMR analysis). Column chromatography [eluent: petroleum ether (60-90 oC)/ethyl acetate = 10/1 (330 mL) to 5/1 (450 mL) at -30 oC] on silica gel afforded (S,E)-6f (0.1912 g, 95%, (S,E)/(R,Z) = 98/2 determined by 1H NMR) as an oil with pleasant flavor: 97% ee (HPLC conditions: Chiralcel IB

31

column, n-hexane/i-PrOH = 98:2, 1.0 mL/min, λ = 214 nm, tR(major) = 38.9 min, tR(minor) = 37.6 min; [α]D20 = +34.1 (c = 1.005, CHCl3); 1H NMR (300 MHz, CDCl3) δ 7.31-7.21 (m, 2H, ArH), 7.21-7.09 (m, 3H, ArH), 5.90 (dtd, J1 = 15.3 Hz, J2 = 6.8 Hz, J3 = 1.0 Hz, 1H, =CH), 5.50 (ddt, J1 = 15.5 Hz, J2 = 7.1 Hz, J3 = 1.4 Hz, 1H, =CH), 4.82 (q, J = 7.2 Hz, 1H, CH), 3.34 (d, J = 6.9 Hz, 2H, CH2), 2.49-2.36 (m, 2H, CH2), 2.34-2.18 (m, 1H, one proton from CH2), 1.95-1.79 (m, 1H, one proton from CH2); the following signals are discernible for (R,Z)-6f: δ 5.82-5.72 (m, 1H, =CH), 5.34-5.24 (m, 1H, CH);

13

C NMR (75 MHz, CDCl3) δ 176.6, 138.8, 133.2, 128.5,

128.14, 128.07, 125.9, 80.2, 37.9, 28.2, 28.1; IR (neat) ν (cm−1) 3084, 3061, 3027, 3001, 2941, 2917, 2840, 1770, 1671, 1602, 1495, 1453, 1422, 1380, 1328, 1290, 1217, 1176, 1121, 1075, 1029, 1008; GC-MS (GC condition: injector: 280 oC; column: DB5 column 30 m × 0.25 mm, temperature programming: 60 oC (2 min), 20 oC/min to 280 o

C, 280 oC (30 min); detector: 280 oC) (70 ev, EI) m/z (%) for (S,E)-6f: tR = 4.1 min:

202 (M+, 19.17), 111 (100); HRMS calcd for C13H14O2 [M+]: 202.0994, found: 202.0995.

7.

Synthesis

of

(S,E)-5-(4-phenyl-1-butenyl)dihydro-2(3H)-furanone

(S,E)-6g

(zj-4-146)

Following Typical Procedure VI, the reaction of AgOTs (0.0142 g, 0.05 mmol, 98%), Au(LB-Phos)Cl (0.0298 g, 0.05 mmol), CHCl3 (5 mL), and (Ra)-5g (0.2156 g, 1.0 mmol)/CHCl3 (5 mL) for 3.0 h afforded (S,E)-6g (0.2101 g, 97%, (S,E)/(R,Z) = 97/3 determined by 1H NMR) [eluent: petroleum ether (60-90 oC)/ethyl acetate = 10/1 (440 mL) to 8/1 (540 mL)] ((S,E)/(R,Z) = 95/5 determined by 1H NMR of crude product) as an oil with pleasant flavor: 97% ee (HPLC conditions: Chiralcel OD-H column, n-hexane/i-PrOH = 90:10, 0.7 mL/min, λ = 214 nm, tR (major) = 27.7 min, tR (minor) = 29.9 min; [α]D20 = +25.4 (c = 1.01, CHCl3); 1H NMR (300 MHz, CDCl3) δ 7.31-7.22 (m, 2H, ArH), 7.21-7.10 (m, 3H, ArH), 5.81 (dtd, J1 = 15.3 Hz, J2 = 6.8 Hz,

32

J3 = 1.1 Hz, 1H, =CH), 5.47 (ddt, J1 = 15.3 Hz, J2 = 7.2 Hz, J3 = 1.4 Hz, 1H, =CH), 4.83 (q, J = 7.2 Hz, 1H, CH), 2.74-2.65 (m, 2H, CH2), 2.51-2.42 (m, 2H, CH2), 2.42-2.22 (m, 3H, one proton from CH2 + CH2), 1.95-1.80 (m, 1H, one proton from CH2); the following signals are discernible for (R,Z)-6g: δ 5.72-5.62 (m, 1H, =CH), 5.11-5.01 (m, 1H, CH);

13

C NMR (75 MHz, CDCl3) δ 176.8, 141.0, 133.9, 128.2,

128.1, 128.0, 125.7, 80.6, 34.9, 33.6, 28.4, 28.3; IR (neat) ν (cm−1) 3081, 3056, 3026, 2998, 2926, 2855, 1774, 1671, 1602, 1496, 1454, 1421, 1379, 1327, 1216, 1176, 1121, 1009; GC-MS (GC condition: injector: 280 oC; column: DB5 column 30 m × 0.25 mm, temperature programming: 60 oC (2 min), 20 oC/min to 280 oC, 280 oC (30 min); detector: 280 oC) (70 ev, EI) m/z (%) for (S,E)-6g: tR = 4.3 min: 216 (M+, 2.67), 91 (100) ; Elemental analysis calcd (%) for C14H16O2: C, 77.75; H, 7.46; Found: C, 77.60; H, 7.47.

8. Synthesis of (S,E)-5-(dodeca-1,11-dien-1-yl)dihydro-2(3H)-furanone (S,E)-6h (zj-5-083)

Following Typical Procedure VI, the reaction of AgOTs (0.0142 mg, 0.05 mmol, 98%), Au(LB-Phos)Cl (0.0299 mg, 0.05 mmol), CHCl3 (5 mL), and (Ra)-6h (0.2504 g, 1.0 mmol)/CHCl3 (5 mL) for 2.0 h afforded (S,E)-6h (0.2356 g, 94%, (S,E)/(R,Z) > 99/1 determined by 1H NMR) [eluent: petroleum ether (60-90 oC)/ethyl acetate = 10/1 (440 mL) to 8/1 (450 mL)] as an oil: 96% ee (SFC (supercritical fluid chromatogram): Chiralcel AD-H column, n-hexane/i-PrOH = 98/2, 0.7 mL/min, λ = 214 nm, tR (major) = 12.9 min, tR (minor) = 12.1 min); [α]D20 = +26.0 (c = 0.99, CHCl3); 1H NMR (300 MHz, CDCl3) δ 5.90-5.69 (m, 2H, =CH), 5.49 (dd, J1 = 15.3 Hz, J2 = 7.2 Hz, 1H, =CH), 5.05-4.81 (m, 3H, =CH2 + CH), 2.57-2.45 (m, 2H, CH2), 2.43-2.30 (m, 1H, one proton from CH2), 2.11-1.88 (m, 5H, one proton from CH2 + CH2 × 2), 1.45-1.17 (m, 12H, CH2 × 6); 13C NMR (75 MHz, CDCl3) δ 177.0, 139.1, 135.6, 127.3, 114.1, 81.1,

33

33.7, 32.0, 29.3, 29.0, 28.81, 28.76, 28.68, 28.65; IR (neat) ν (cm−1) 3075, 2976, 2925, 2854, 1778, 1673, 1640, 1459, 1436, 1422, 1374, 1327, 1300, 1216, 1176, 1123, 1008; GC-MS (GC condition: injector: 280 oC; column: DB5 column 30 m × 0.25 mm, temperature programming: 60 oC (2 min), 20 oC/min to 280 oC, 280 oC (30 min); detector: 280 oC, (70 ev, EI) m/z (%) for (S,E)-6h: tR = 4.60 min: 250 (M+, 0.42), 41 (100); Elemental analysis calcd (%) for C16H26O2: C, 76.75; H, 10.47; Found: C, 76.73; H, 10.77.

9. Synthesis of (S,E)-5-(10-(tert-butyldimethylsilyl)-1-decen-9-yn-1-yl)dihydro-2 (3H)-furanone (S,E)-6i (zj-6-188)

Following Typical Procedure VI, the reaction of AgOTs (0.0142 g, 0.05 mmol), Au(LB-Phos)Cl (0.0300 g, 0.05 mmol), CHCl3 (5 mL) and (Ra)-5i (0.3330 g, 1.0 mmol)/CHCl3 (5 mL) for 3.0 h afforded (S,E)-6i (0.3206 g, 96%, (S,E)/(R,Z) = 97/3 determined by 1H NMR) [eluent: petroleum ether (60-90 oC)/ethyl acetate = 15/1 (480 mL) to 10/1 (850 mL)] ((S,E)/(R,Z) = 97/3 determined by 1H NMR of crude product) as an oil: 97% ee (HPLC conditions: Chiralcel OJ-H column, n-hexane/i-PrOH = 100/1, 0.3 mL/min, λ = 214 nm, tR (major) = 29.5 min, tR (minor) = 28.5 min); [α]D20 = +17.6 (c = 1.00, CHCl3); 1H NMR (300 MHz, CDCl3) δ 5.78 (dtd, J1 = 15.3 Hz, J2 = 7.2 Hz, J3 = 0.8 Hz, 1H, =CH), 5.47 (ddt, J1 = 15.3 Hz, J2 = 6.9 Hz, J3 = 1.4 Hz, 1H, =CH), 4.87 (q, J = 7.1 Hz, 1H, CH), 2.57-2.47 (m, 2H, CH2), 2.44-2.28 (m, 1H, one proton from CH2), 2.20 (t, J = 6.9 Hz, 2H, CH2), 2.10-1.87 (m, 3H, CH2 + one proton from CH2), 1.55-1.22 (m, 8H, CH2 × 4), 0.90 (s, 9H, CH3 × 3), 0.05

(s, 6H, CH3 ×

2); the following signals are discernible for (R,Z)-6i: δ 5.69-5.60 (m, 1H, =CH), 5.27-5.18 (m, 1H, CH);

13

C NMR (75 MHz, CDCl3) δ 176.9, 135.4, 127.4, 107.9,

82.3, 81.0, 31.9, 28.7, 28.6, 28.5, 28.39, 28.36, 28.3, 26.0, 19.6, 16.4, -4.6; IR (neat) ν (cm−1) 2929, 2856, 2172, 1776, 1673, 1461, 1361, 1326, 1249, 1174, 1008; GC-MS (GC condition: injector: 280 oC; column: DB5 column 30 m × 0.25 mm, temperature

34

programming: 60 oC (2 min), 20 oC/min to 280 oC, 280 oC (30 min); detector: 280 oC) (70 ev, EI) m/z (%) for (S,E)-6i: tR (major) = 5.41 min, m/z (%) 277 (M+ - t-Bu, 10.23), 75 (100); for (R,Z)-6i: tR (minor) = 5.36 min, m/z (%) 277 (M+ - t-Bu, 8.13), 75 (100); Elemental analysis calcd (%) for C20H34O2Si: C, 71.80; H, 10.24; Found: C, 71.57; H, 10.18.

10. Synthesis of (R,E)-5-(1-decenyl)dihydro-2(3H)-furanone (R,E)-6j (zj-5-014)

Following Typical Procedure VI, the reaction of AgOTs (0.0142 g, 0.05 mmol), AuCl(LB-Phos) (0.0299 g, 0.05 mmol), CHCl3 (5 mL), and (Sa)-5j (0.2239 g, 1.0 mmol)/CHCl3 (5 mL) (for synthesis of compound (Sa)-5j, see page 68) for 3.0 h afforded (R,E)-6j11 (0.2094 g, 94%, (R,E)/(S,Z) = 97/3 determined by 1H NMR) [eluent: petroleum ether (60-90 oC)/ethyl acetate = 10/1 (220 mL) to 8/1 (450 mL)] ((R,E)/(S,Z) = 97/3 determined by 1H NMR of crude product) as an oil with pleasant flavor: 95% ee (HPLC conditions: Chiralcel OJ-H column, n-hexane/i-PrOH = 100/1, 1.0 mL/min, λ = 214 nm, tR (major) = 12.9 min, tR (minor) = 16.2 min); [α]D20 = -27.4 (c = 1.00, CHCl3); (Lit.10 [α]D26 = -31.2 (c = 2.237, CHCl3)); 1H NMR (300 MHz, CDCl3) δ 5.81 (dtd, J1 = 15.3 Hz, J2 = 6.9 Hz, J3 = 0.8 Hz, 1H, =CH), 5.49 (ddt, J1 = 15.2 Hz, J2 = 7.1 Hz, J3 = 1.5 Hz, 1H, =CH), 4.89 (q, J = 7.1 Hz, 1H, CH), 2.58-2.49 (m, 2H, CH2), 2.45-2.31 (m, 1H, one proton from CH2), 2.12-1.90 (m, 3H, CH2 + one proton from CH2), 1.46-1.18 (m, 12H, CH2 × 6), 0.88 (t, J = 6.9 Hz, 3H, CH3); the following signals are discernible for (S,Z)-6j: δ 5.72-5.61 (m, 1H, =CH), 5.30-5.20 (m, 1H, CH);

13

C NMR (75 MHz, CDCl3) δ 176.9, 135.4, 127.3, 80.9, 31.9, 31.7, 29.2,

29.0, 28.9, 28.7, 28.6, 28.5, 22.5, 13.9; IR (neat) ν (cm−1) 2955, 2926, 2854, 1778, 1673, 1460, 1422, 1378, 1327, 1296, 1216, 1176, 1123, 1011; GC-MS (GC condition: injector: 280 oC; column: DB5 column 30 m × 0.25 mm, temperature programming: 60 oC (2 min), 20 oC/min to 280 oC, 280 oC (30 min); detector: 280 oC) (70 ev, EI) m/z (%) for (R,E)-6j: tR (major) = 4.03 min: 224 (M+, 0.72), 111 (100); for (S,Z)-6j tR

35

(minor) = 3.99 min: 224 (M+, 1.18), 111 (100).

11. Gram scale synthesis of (S,E)-6b (zj-6-160)

To a dry Schlenk tube were added AgOTs (0.0426 g, 0.15 mmol, weighed in glove box, 98%), Au(LB-Phos)Cl (0.0896 g, 0.15 mmol), and CHCl3 (30 mL) under nitrogen atmosphere sequentially. After stirring at room temperature for 15 min, the reaction was cooled down to -20 oC and then (Ra)-5b (1.6817 g, 10.0 mmol) and CHCl3 (10 mL) (for synthesis of compound (Ra)-5b, see page 74) were added. After being continuously stirred at –20 oC for 15 h, the reaction was complete as monitored by TLC. The resulting mixture was warmed up to room temperature. Filtration through a short column of silica gel [eluent: Et2O (25 mL ×3)] and evaporation afforded a crude mixture of (S,E)-6b and (R,Z)-6b ((S,E)/(R,Z) = 98/2 determined by 1

H NMR analysis). Column chromatography on silica gel [(eluent: petroleum ether

(60-90 oC)/ethyl acetate = 15/1 (500 mL) to 10/1 (550 mL)] afforded (S,E)-6b (1.6615 g, 99%, (S,E)/(R,Z) = 98/2 determined by 1H NMR) as a liquid with pleasant flavor: 97% ee (HPLC conditions: Chiralcel OJ-H column, n-hexane/i-PrOH = 200/1, 1.0 mL/min, λ = 214 nm, tR (major) = 26.4 min, tR (minor) = 23.7 min); [α]D20 = +37.1 (c = 1.00, CHCl3); 1H NMR (300 MHz, CDCl3) δ 5.81 (dtd, J1 = 15.3 Hz, J2 = 6.8 Hz, J3 = 1.0 Hz, 1H, =CH), 5.49 (ddt, J1 = 15.3 Hz, J2 = 7.2 Hz, J3 = 1.5 Hz, 1H, =CH), 4.90 (q, J = 7.2 Hz, 1H, CH), 2.60-2.49 (m, 2H, CH2), 2.46-2.31 (m, 1H, one proton from CH2), 2.12-1.90 (m, 3H, CH2 + one proton from CH2), 1.46-1.24 (m, 4H, CH2 × 2), 0.90 (t, J = 7.2 Hz, 3H, CH3); the following signals are discernible for (R,Z)-6b: δ 5.70-5.62 (m, 1H, =CH), 5.31-5.21 (m, 1H, CH); 13C NMR (75 MHz, CDCl3) δ 176.9, 135.4, 127.3, 81.0, 31.6, 30.7, 28.7, 28.5, 21.9, 13.7.

12. Synthesis of (R,E)-5-(1-octenyl)dihydro-2(3H)-furanone (R,E)-6m (zj-9-053)

36

Following Typical Procedure VI, the reaction of AgOTs (0.0142 g, 0.05 mmol, 98%), Au(LB-Phos)Cl (0.0300 g, 0.05 mmol), CHCl3 (5 mL), and (Sa)-5m (0.1964 g, 1.0 mmol)/CHCl3 (5 mL) for 3.0 h afforded (R,E)-6m (0.1891 g, 96%, (R,E)/(S,Z) = 97/3 determined by 1H NMR) [eluent: petroleum ether (60-90 oC)/ethyl acetate = 10/1 (550 mL) to 7/1 (480 mL)] ((R,E)/(S,Z) = 97/3 determined by 1H NMR of crude product) as a liquid with pleasant flavor: 96% ee (HPLC conditions: Chiralcel OJ-H column, n-hexane/i-PrOH = 97/3, 1.0 mL/min, λ = 214 nm, tR (major) = 12.5 min, tR (minor) = 14.5 min); [α]D20 = -32.6 (c = 0.995, CHCl3); 1H NMR (300 MHz, CDCl3) δ 5.81 (dt, J1 = 15.3 Hz, J2 = 7.1 Hz, 1H, =CH), 5.49 (ddt, J1 = 15.3 Hz, J2 = 7.2 Hz, J3 = 1.2 Hz, 1H, =CH), 4.90 (q, J = 7.2 Hz, 1H, CH), 2.61-2.48 (m, 2H, CH2), 2.46-2.32 (m, 1H, one proton from CH2), 2.15-1.90 (m, 3H, CH2 + one proton from CH2), 1.46-1.16 (m, 8H, CH2 × 4), 0.88 (t, J = 6.6 Hz, 3H, CH3); the following signals are discernible for (S,Z)-6m: δ 5.71-5.61 (m, 1H, =CH), 5.32-5.22 (m, 1H, CH);

13

C

NMR (75 MHz, CDCl3) δ 176.8, 135.3, 127.2, 80.9, 31.8, 31.3, 28.5, 28.44, 28.41, 22.2, 13.7; IR (neat) ν (cm−1) 2956, 2927, 2856, 1777, 1673, 1459, 1420, 1379, 1327, 1216, 1179, 1132, 1076, 1009; GC-MS (GC condition: injector: 280 oC; column: DB5 column 30 m × 0.25 mm, temperature programming: 60 oC (2 min), 20 oC/min to 280 o

C, 280 oC (30 min); detector: 280 oC) (70 ev, EI) m/z (%) for (R,E)-6m: tR (major) =

6.65 min: 196 (M+, 0.88), 111 (100); for (S,Z)-6m: tR (minor) = 6.57 min: 196 (M+, 1.68), 111 (100). HRMS calcd for C12H20O2 [M+]: 196.1463, found: 196.1466.

Synthesis of naturally occurring xestospongienes 1. Synthesis of racemic xestospongiene Synthesis of 9-((tert-butyldimethylsilyl)oxy)non-1-yn-3-ol12 rac-8 (zj-7-083)

37

To a flame-dried three-neck flask equipped with a reflux condenser containing Mg turnings (2.6545 g, 110.5 mmol) was added THF (110 mL) under nitrogen atmosphere. After the reaction was initiated with a grain of I2 and a little amount of EtBr, EtBr [8.3 mL (including the EtBr used above for initiation), d = 1.46 g cm-3, 12.118 g, 111.17 mmol] was then added dropwise within 30 min. After the addition was complete, the resulting mixture was stirred for 2.5 h at room temperature, and then a stream of ethyne was bubbled through the resulting solution at -35 oC. The ethyne gas was introduced for 30 min at a rate that the temperature was kept under 10 o

C using a dry ice-acetone bath. Then the gas of ethyne was introduced for an extra 30

min before removing the dry ice-acetone bath. The resulting mixture was warmed up to

room

temperature

for

30

min

and

a

solution

of

7-((tert-butyldimethylsilyl)oxy)heptanal 7 (readily available from 1,7-heptanediol in 2 steps)13 (15.8817 g, 65 mmol) in THF (25 mL) was added dropwise within 30 min. When the reaction was complete after 12 h as monitored by TLC, a saturated aqueous solution of NH4Cl (30 mL) was added dropwise at rt. The organic layer was separated and the aqueous layer was extracted with Et2O (50 mL × 3). The combined organic layer was washed with H2O and brine and dried over anhydrous Na2SO4. After filtration and evaporation, the residue was purified by chromatography [eluent: petroleum ether (60-90 oC)/ethyl acetate = 100/1 (350 mL) to 50/1 (500 mL) to 15/1 (500 mL × 2)] on silica gel afforded 9-((tert-butyldimethylsilyl)oxy)non-1-yn-3-ol rac-8 (14.8471 g, 85%) as a liquid: 1H NMR (300 MHz, CDCl3) δ 4.32 (t, J = 6.6 Hz, 1H, CH), 3.57 (t, J = 6.6 Hz, 2H, CH2), 2.68 (s, 1H, OH), 2.42 (d, J = 2.1 Hz, 1H, ≡CH), 1.73-1.62 (m, 2H, CH2), 1.54-1.38 (m, 4H, CH2 × 2), 1.35-1.26 (m, 4H, CH2 × 2), 0.86 (s, 9H, CH3 × 3), 0.01 (s, 6H, CH3 × 2); 13C NMR (75 MHz, CDCl3) δ 85.1, 72.7, 63.2, 62.0, 37.5, 32.6, 29.0, 25.9, 25.6, 24.9, 18.3, -5.3; IR (neat) ν (cm−1) 3355, 3311, 2930, 2857, 2114, 1472, 1463, 1388, 1361, 1255, 1099, 1006; MS (ESI) m/z 271 [M + H]+; HRMS (ESI) calcd. for C15H31O2Si+ [M + H]+: 271.2088, found: 271.2080.

Synthesis of 7-methoxynon-8-yn-1-ol 14 rac-9 (zj-7-106)

38

To a dry Schlenk flask were added 8 (2.9494 g, 11 mmol) and THF (33 mL) under nitrogen atmosphere. The solution was cooled to 0 °C with an ice bath, and NaH (0.4404 g, 60% dispersion in mineral oil, 11 mmol,) was added carefully. After the addition was complete, the cooling bath was removed and the resulting mixture was stirred for 30 min. Then MeI (0.83 mL, d = 2.28 g cm-3, 1.8735 g, 13.2 mmol, 99%) was added dropwise at 0 °C within 2 min. The reaction was warmed up to room temperature again by removing the ice-bath. After stirring for 5 h, the reaction was complete as monitored by TLC and then 3 M HCl (5.5 mL) was added slowly at 0 °C. The reaction was monitored by TLC again after 1.5 h to make sure that the TBS-group was removed completely. The mixture was quenched with water (11 mL) and then extracted with EtOAc (20 mL × 3). The combined organic layer was washed with brine and dried over anhydrous Na2SO4. After filtration and evaporation, the residue was purified by chromatography [eluent: petroleum ether (60-90 oC)/ethyl acetate = 10/1 (550 mL) to 5/1 (600 mL) to 3/1 (480 mL)] on silica gel to afford 7-methoxynon-8-yn-1-ol rac-9 (1.6238 g, 88%) as a liquid: 1H NMR (300 MHz, CDCl3) δ 3.94 (td, J1 = 6.5 Hz, J2 = 2.0 Hz, 1H, CH), 3.63 (t, J = 6.6 Hz, 2H, CH2), 3.41 (s, 3H, CH3), 2.60-2.38 (bs, 1H, OH), 2.46 (d, J = 1.8 Hz, 1H, ≡CH), 1.81-1.66 (m, 2H, CH2), 1.66-1.29 (m, 8H, CH2 × 4); 13C NMR (75 MHz, CDCl3) δ 82.6, 73.7, 71.0, 62.7, 56.3, 35.3, 32.5, 29.0, 25.5, 25.0; IR (neat) ν (cm−1) 3384, 3299, 2934, 2859, 2822, 2112, 1465, 1336, 1107, 1092, 1058; MS (ESI) m/z 171 [M + H]+; HRMS (ESI) calcd. for C10H19O2+ [M + H]+: 171.1380, found:171.1383.

Synthesis of 7-methoxynon-8-ynal15 rac-10 (zj-7-110)

To a three-necked flask were added Fe(NO3)3∙9H2O (0.2962 g, 0.72 mmol, 98%),

39

NaCl (0.0420 g, 0.72 mmol), TEMPO (0.1146 g, 0.72 mmol, 98%), and DCM (75 mL) subsequently. An oxygen balloon was equipped and then a solution of rac-9 (1.5279 g, 9 mmol) in 15 mL of DCM was added dropwise via an addition funnel at 25 oC within 10 min in oxygen atmosphere from the balloon. The resulting mixture was stirred for 12.5 h until the reaction was complete as monitored by TLC. After filtration through a short column of silica gel [eluent: Et2O (20 mL × 3)] and evaporation, the residue was purified by chromatography [eluent: petroleum ether (60-90 oC)/ethyl acetate = 30/1 (500 mL) to 20/1 (500 mL) to 10/1 (500 mL)] on silica gel to afford 7-methoxynon-8-ynal rac-10 (0.9301 g, 62%) as a liquid: 1H NMR (300 MHz, CDCl3) δ 9.76 (t, J = 1.8 Hz, 1H, CHO), 3.93 (td, J1 = 6.5 Hz, J2 = 1.7 Hz, 1H, CH), 3.41 (s, 3H, CH3), 2.40-2.41 (m, 3H, ≡CH + CH2), 1.77-1.59 (m, 4H, CH2 × 2), 1.55-1.43 (m, 2H, CH2), 1.43-1.31 (m, 2H, CH2);

13

C NMR (75 MHz, CDCl3) δ 201.7, 81.7, 73.3,

70.0, 55.5, 42.9, 34.3, 27.9, 23.9, 21.0; IR (neat) ν (cm−1) 3284, 2986, 2940, 2862, 2823, 2722, 2109, 1724, 1465, 1410, 1391, 1336, 1192, 1156, 1108, 1091; MS (ESI) m/z 169 [M + H]+; HRMS (ESI) calcd. for C10H17O2+ [M + H]+: 169.1223, found: 169.1220.

Synthesis of 1,1-dibromo-8-methoxydec-1-en-9-yne rac-1c16 (zj-7-112)

Typical Procedure VII: To a dry Schlenk flask were added aldehyde rac-10 (0.8727 g, 5.2 mmol) and DCM (55 mL, dry) under nitrogen atmosphere. The resulting solution was cooled to 0 °C with an ice bath followed by the addition of CBr4 (2.5884 g, 7.8 mmol). Then a solution of PPh3 (4.1697 g, 15.6 mmol, 98%) in DCM (20 mL) was added dropwise at 0 °C within 0.5 h. The resulting mixture was warmed up to room temperature naturally. After 1 h the reaction was complete as monitored by TLC. Then the resulting mixture was diluted with petroleum ether (75 mL) forming white precipitate. The precipitate was filtrated off and washed with petroleum ether (15 mL × 3). After combining the filtrate and evaporation, the residue

40

was purified by chromatography [eluent: petroleum ether/ethyl acetate = 100/1 (400 mL) to 50/l (500 mL) to 30/l (200 mL)] on silica gel to afford rac-1c (1.5451 g, 92%) as a liquid: 1H NMR (300 MHz, CDCl3) δ 6.38 (t, J = 7.2 Hz, 1H, =CH), 3.93 (td, J1 = 6.5 Hz, J2 = 2.1 Hz, 1H, CH), 3.41 (s, 3H, CH3), 2.45 (d, J = 2.1 Hz, 1H, ≡CH), 2.10 (q, J = 7.2 Hz, 2H, CH2), 1.77-1.66 (m, 2H, CH2), 1.53-1.27 (m, 6H, CH2 × 3),

13

C

NMR (75 MHz, CDCl3) δ 138.6, 88.6, 82.6, 73.8, 70.9, 56.4, 35.3, 32.8, 28.6, 27.6, 24.7; IR (neat) ν (cm−1) 3301, 2985, 2932, 2858, 2822, 2110, 1622, 1463, 1335, 1273, 1261, 1196, 1152, 1109; MS (EI) m/z (%) 325 {[M (81Br81Br) - H]+, 0.035}, 323 {[M (79Br81Br) - H]+, 0.069}, 321 {[M (79Br79Br) - H]+, 0.036}, 201 {[M (81Br81Br) C8H13O]+, 5.37}, 199 {[M (79Br81Br) - C8H13O]+, 12.31}, 197 {[M (79Br79Br) C8H13O]+, 5.62}, 69 (100); HRMS (EI) calcd for C11H1579Br79BrO [M - H]+: 320.9490, found: 320.9499.

Synthesis of methyl 14,14-dibromo-7-methoxy-4,5,13-tetradecatrienoate rac-4ck (zj-7-114)

To a flame-dried Schlenk tube with a polytetrafluoroethylene plug were added CuBr2 (0.1803 g, 0.8 mmol, 99%), rac-3a (1.5497 g, 6.0 mmol, 98%), rac-1c (1.2943 g, 4.0 mmol)/dioxane (6 mL), and methyl 4-oxobutanoate 2k17 (0.6965 g, 6 mmol)/dioxane (6 mL) sequentially under nitrogen atmosphere. The Schlenk tube was then sealed by screwing the polytetrafluoroethylene plug tightly. The reaction was complete after being stirred in an oil bath preheated at 130 oC for 17 h as monitored by TLC. The resulting mixture was cooled down to room temperature, diluted with Et2O (50 mL), and washed with an aqueous solution of hydrochloric acid (10 mL × 3, 3 M). The organic layer was separated and the aqueous layer was extracted with Et2O (10 mL). The combined organic layer was washed with brine and dried over anhydrous Na2SO4. After filtration and evaporation, the residue was purified by

41

chromatography [eluent: petroleum ether (60-90 oC)/ethyl acetate = 50/1 (500 mL) to 30/1 (500 mL) to 15/1 (600 mL)] on silica gel to afford rac-4ck (1.0789 g, 64%, d.r. = 1.07 : 1 determined by 1H NMR) as a liquid: 1H NMR (300 MHz, CDCl3) δ 6.39 (td, J1 = 7.2 Hz, J2 = 2.4 Hz, 1H, =CH), 5.35-5.19 (m, 1H, =CH), 5.06-4.94 (m, 1H, =CH), 3.68 (s, 3H, CH3), 3.58 (q, J = 6.9 Hz, 1H, CH), [3.32 (s, 1.43H), 3.30 (s, 1.53H), 3H, CH3], 2.51-2.28 (m, 4H, CH2 × 2), 2.16-2.02 (m, 2H, CH2), 1.70-1.18 (m, 8H, CH2 × 4); IR (neat) ν (cm−1) 2927, 2856, 2819, 1962, 1741, 1462, 1436, 1364, 1254, 1197, 1160, 1087; MS (ESI) m/z 449 [M (81Br81Br) + Na] +, 447 [M (79Br81Br) + Na]+, 445 [M (79Br79Br) + Na]+; HRMS (ESI) calcd. for C16H2479Br79BrNaO3+ [M (79Br79Br) + Na] +: 444.9984, found: 444.9966.

Synthesis

of

14,14-dibromo-7-methoxy-4,5,13-tetradecatrienoic

acid

rac-5k

(zj-7-121)

Following Typical Procedure II, the reaction of rac-4ck (0.9959 g, 2.35 mmol), EtOH/H2O = 1:1 by volume (pre-mixed by using 12 mL of H2O and 12 mL of EtOH) and LiOH∙H2O (0.1560 g, 3.525 mmol, 95%) for 1.5 h afforded rac-5k (0.9027 g, 94%, d.r. = 1.07:1 determined by 1H NMR) [eluent: petroleum ether (60-90 oC)/ethyl acetate = 10/1 (440 mL) to 7/1 (560 mL) to 5/1 (600 mL) to 3/1 (120 mL)] as an oil: 1

H NMR (300 MHz, CDCl3) δ 11.23 (bs, 1H, COOH), 6.38 (td, J1 = 7.3 Hz, J2 = 1.9

Hz, 1H, =CH), 5.34-5.21 (m, 1H, =CH), 5.07-4.97 (m, 1H, =CH), 3.60 (q, J = 6.7 Hz, 1H, CH), [3.33 (s, 1.45H), 3.31 (s, 1.55H), 3H, CH3], 2.56-2.44 (m, 2H, CH2), 2.41-2.28 (m, 2H, CH2), 2.15-2.03 (m, 2H, CH2), 1.71-1.23 (m, 8H, CH2 × 4); IR (neat) ν (cm−1) 3716-2200 (COOH), 3022, 2977, 2931, 2856, 2820, 2651, 1963, 1712, 1435, 1417, 1336, 1277, 1250, 1208, 1157, 1108, 1086; MS (ESI) m/z 435 [M (81Br81Br) + Na]+, 433 [M (79Br81Br) + Na]+, 431 [M (79Br79Br) + Na]+; HRMS (ESI) calcd. for C15H2279Br79BrNaO3 + [M (79Br79Br) + Na]+: 430.9828, found:430.9810.

42

Synthesis of 5-(10’,10’-dibromo-3’-methoxy-1’ (E),9’-decadien-1’-yl)dihydro-2 (3H)-furanone rac-xestospongiene (zj-7-158)

Typical Procedure VIII: To a dry Schlenk tube were added AgOTs (0.0285 g, 0.1 mmol, weighed in glove box, 98%), AuCl(LB-Phos) (0.0597 g, 0.1 mmol), and CHCl3 (5 mL) under nitrogen atmosphere sequentially. After stirring at room temperature for 15 min, the reaction was cooled down to -30 oC and then rac-5k (0.4093 g, 1.0 mmol) and CHCl3 (5 mL) were added. The reaction mixture was then continuously stirred at -30 oC for 24 h as monitored by TLC. The reaction was warmed up to room temperature. Filtration through a short column of silica gel [eluent: Et2O (20 mL × 3)] and evaporation afforded a crude mixture of (E)-6k and (Z)-6k (E/Z = 97:3 determined by 1H NMR analysis). Column chromatography on silica gel [eluent: petroleum ether (60-90 oC)/ethyl acetate = 15/1 (550 mL) to 10/1 (550 mL) to 8/1 (540 mL) to 5/1 (600 mL)] afforded the impure rac-xestospongiene (0.3886 g). The impure rac-xestospongiene was purified again on silica gel [eluent: petroleum ether (60-90 oC)/ethyl acetate/dichloromethane = 150/10/1 (480 mL) to 100/10/1 (550 mL) to 80/10/1 (540 mL × 3)] to give pure rac-xestospongiene (0.3792 g, 93%, E/Z = 99:1 determined by 1H NMR, d.r. = 1.07:1 determined by quantitative

13

C NMR

analysis) as a liquid: 1H NMR (300 MHz, CDCl3) δ 6.39 (t, J = 7.4 Hz, 1H, =CH), 5.80-5.57 (m, 2H, =CH × 2), 4.98 (q, J = 6.6 Hz, 1H, CH), 3.68-3.50 (m, 1H, CH), 3.26 (s, 3H, CH3), 2.66-2.37 (m, 3H, CH2 + one proton of CH2), 2.16-1.93 (m, 3H, CH2 + one proton of CH2), 1.67-1.17 (m, 8H, CH2 × 4); the following signals are discernible for (Z)-6k: δ 5.56-5.46 (m, 1H, CH), 5.35-5.26 (m, 1H, CH); IR (neat) ν (cm−1) 2931, 2857, 2821, 1777, 1461, 1422, 1326, 1176, 1113, 1088, 1012; MS (ESI) m/z 413 [M (81Br81Br) + H]+, 411 (M [79Br81Br) + H]+, 409 [M (79Br79Br) + H]+; HRMS (ESI) calcd for C15H2379Br79Br O3+ [M (79Br79Br) + H]+: 409.0008, found:

43

409.0007.

2. Asymmetric synthesis of xestospongienes E-H. I. Synthesis of optically active propargylic alcohols (R)-8 and (S)-8. a. Synthesis of (R)-9-((tert-butyldimethylsilyl)oxy)non-1-yn-3-ol3 (R)-8 (zj-7-113)

Typical Procedure IX: To a three-necked flask were added rac-8 (10.8189 g, 40 mmol) and n-hexane (340 mL). Then vinyl acetate (22.2 mL, d = 0.93 g cm-3, 20.646 g, 240.07 mmol) and Novozym-435 (2.7051 g, 25% w) were added sequentially. The reaction mixture was filtrated through a short column of silica gel [eluent: Et2O (30 mL × 3)] after being stirred in an oil bath preheated at 30 oC for 21 h as monitored by TLC. After evaporation of the filtrate, the residue was purified by chromatography [eluent: petroleum ether (60-90 oC)/ethyl acetate = 100/1 (300 mL) to 50/1 (500 mL) to 30/1 (500 mL) to 15/1 (500 mL) to 10/1 (500 mL × 2)] on silica gel to afford (S)-11 (6.6618 g, 53%) as a liquid and (R)-8 (4.3075 g, 40%) as a liquid. For (S)-11: 1H NMR (300 MHz, CDCl3) δ 5.33 (td, J1 = 6.8 Hz, J2 = 2.2 Hz, 1H, CH), 3.59 (t, J = 6.5 Hz, 2H, CH2), 2.44 (d, J = 2.4 Hz, 1H, ≡CH), 2.08 (s, 3H, CH3), 1.81-1.71 (m, 2H, CH2), 1.56-1.29 (m, 8H, CH2 × 4), 0.88 (s, 9H, CH3 × 3), 0.04 (s, 6H, CH3 × 2). For (R)-8: > 99% ee (determined by the corrsponding acylation product (R)-11); [α]D20 = +2.0 (c = 0.95, CHCl3); 1H NMR (300 MHz, CDCl3) δ 4.41-4.30 (m, 1H, CH), 3.58 (t, J = 6.5 Hz, 2H, CH2), 2.44 (d, J = 2.1 Hz, 1H, ≡CH), 2.24 (bs, 1H, OH), 1.77-1.63 (m, 2H, CH2), 1.58-1.24 (m, 8H, CH2 × 4), 0.87 (s, 9H, CH3 × 3), 0.03 (s, 6H, CH3 × 2); 13C NMR (75 MHz, CDCl3) δ 85.0, 72.8, 63.2, 62.2, 37.5, 32.7, 29.0, 25.9, 25.6, 25.0, 18.3, -5.3; IR (neat) ν (cm−1) 3402, 3312, 2931, 2858, 2112, 1471, 1461, 1389, 1361, 1256, 1100, 1006; MS (ESI) m/z 293 [M + Na]+, 271 [M + H]+; HRMS (ESI) calcd for C15H30NaO2Si+ [M + Na]+: 293.1907, found: 293.1910.

44

Acetylation

for

determination

of

the

ee

value

of

(R)-8:

synthesis

of

(R)-9-((tert-butyldimethylsilyl)oxy)non-1-yn-3-yl acetate (R)-1118 (zj-7-117)

To a dry Schlenk tube were added (R)-8 (0.0802 g, 0.3 mmol, prepared above), Et2O (3 mL), DMAP (0.0128 g, 0.105 mmol), triethylamine (62 μL, d = 0.73 g cm-3, 0.0453 g, 0.448 mmol), and acetic anhydride (43 μL, d = 1.08 g cm-3, 0.0464 g, 0.455 mmol) sequentially under nitrogen atmosphere. After continuous stirring for 10 h at room temperature, the reaction was complete as monitored by TLC. After evaporation, the residue was purified by chromatography [eluent: petroleum ether (60-90 oC)/ethyl acetate = 20/1 (250 mL)] on silica gel to afford (R)-11 (0.0897 g, 97%) as a liquid: >99% ee [GC conditions: CP-Chirasil-DEX CB column (25 m × 0.25 mm × 0.25 μm); carrier: N2 (10.0 psi); injector: 145 oC; detector (FID, H2): 200 oC; oven temperature: 50 oC (8 min), 50 oC to 150 oC (3 oC/min, 5 min), 150 oC to 180 oC ; tR (major) = 55.9 min]; [α]D20 = +43.9 (c = 0.99, CHCl3); 1H NMR (300 MHz, CDCl3) δ 5.32 (td, J1 = 6.7 Hz, J2 = 2.2 Hz, 1H, CH), 3.58 (t, J = 6.5 Hz, 2H, CH2), 2.44 (d, J = 2.4 Hz, 1H, ≡CH), 2.07 (s, 3H, CH3), 1.80-1.69 (m, 2H, CH2), 1.55-1.26 (m, 8H, CH2 × 4), 0.87 (s, 9H, CH3 × 3), 0.03 (s, 6H, CH3 × 2);

13

C NMR (75 MHz, CDCl3) δ

169.9, 81.2, 73.4, 63.7, 63.1, 34.5, 32.6, 28.8, 25.9, 25.6, 24.8, 20.9, 18.3, -5.3; IR (neat) ν (cm−1) 3312, 2932, 2858, 2123, 1746, 1472, 1463, 1371, 1232, 1098, 1022; MS (ESI) m/z 335 [M + Na]+, 313 [M + H]+; HRMS (ESI) calcd for C17H32NaO3Si+ [M + Na]+: 335.2013, found: 335.2010.

b. Synthesis of (S)-9-((tert-butyldimethylsilyl)oxy)non-1-yn-3-ol (S)-8 (zj-7-118, zj-7-120, zj-7-140)

45

Typical Procedure X: 19 To a round-bottom flask were added (S)-11 (6.6618 g, 21.3 mmol, prepared above, see page 46) and MeOH (22 mL). Then K2CO3 (4.4087 g, 31.95 mmol) was added. The reaction was complete as monitored by TLC after being stirred at room temperature for 0.5 h. K2CO3 was filtrated off and washed with Et2O (15 mL ×5). After combining the filtrate and evaporation, the residue was purified by chromatography [eluent: petroleum ether (60-90 oC)/ethyl acetate = 100/1 (300 mL) to 50/1 (400 mL) to 30/1 (500 mL) to 10/1 (900 mL)] on silica gel to afford (R)-9-((tert-butyldimethylsilyl)oxy)non-1-yn-3-ol (S)-8 (5.6511 g, 98%) as a liquid, which was then submitted to next step without further characterization: 1H NMR (300 MHz, CDCl3) δ 4.38-4.30 (m, 1H, CH), 3.58 (t, J = 6.5 Hz, 2H, CH2), 2.46-2.39 (m, 2H, OH + ≡CH), 1.74-1.64 (m, 2H, CH2), 1.56-1.27 (m, 8H, CH2 ×4), 0.87 (s, 9H, CH3 ×3), 0.02 (s, 6H, CH3 ×2), Following Typical Procedure IX, the reaction of (S)-8 (5.6305 g, 20.8 mmol, prepared above), Novozym-435 (1.1257 g, 20% w), and vinyl acetate (11.55 mL, d = 0.93 g cm-3, 10.7415 g, 124.9 mmol) in n-hexane (190 mL) for 1.67 h afforded (S)-9-((tert-butyldimethylsilyl)oxy)non-1-yn-3-yl acetate (S)-11 (4.8175 g, 74%) [eluent: petroleum ether (60-90 oC)/ethyl acetate = 100/1 (500 mL) to 50/1 (500 mL × 2) to 30/1 (300 mL) to 10/1 (550 mL) to 5/1 (300 mL)] as a liquid: > 99% ee [GC conditions: CP-Chirasil-DEX CB column (25 m × 0.25 mm × 0.25 μm); carrier: N2 (10.0 psi); injector: 145 oC; detector (FID, H2): 200 oC; oven temperature: 50 oC (8 min), 50 oC to 150 oC (3 oC/min, 5 min), 150 oC to 180 oC; tR (major) = 56.3 min]; [α]D20 = -45.5 (c = 0.995, CHCl3); 1H NMR (300 MHz, CDCl3) δ 5.32 (td, J1 = 6.6 Hz, J2 = 1.8 Hz, 1H, CH), 3.58 (t, J = 6.5 Hz, 2H, CH2), 2.44 (d, J = 2.1 Hz, 1H, ≡CH), 2.07 (s, 3H, CH3), 1.80-1.70 (m, 2H, CH2), 1.56-1.27 (m, 8H, CH2 × 4), 0.88 (s, 9H,

46

CH3 × 3), 0.03 (s, 6H, CH3 × 2); 13C NMR (75 MHz, CDCl3) δ 169.9, 81.2, 73.4, 63.7, 63.1, 34.4, 32.6, 28.8, 25.9, 25.6, 24.8, 20.9, 18.3, -5.3; IR (neat) ν (cm−1) 3312, 2931, 2858, 2123, 1746, 1472, 1463, 1435, 1372, 1232, 1098, 1022; MS (ESI) m/z 335 [M + Na]+, 313 [M + H]+; HRMS (ESI) calcd for C17H32NaO3Si+ [M + Na]+: 335.2013, found: 335.2014. Following Typical Procedure X, the reaction of (S)-11 (4.7490 g, 15.2 mmol, prepared above), K2CO3 (3.1471 g, 22.8 mmol), and MeOH (16 mL) for 0.5 h afforded (S)-8 (4.0801 g, 99%; 38% for 4 steps) [eluent: petroleum ether (60-90 o

C)/ethyl acetate = 50/1 (200 mL) to 30/1 (300 mL) to 15/1 (500 mL) to 10/1 (600

mL)] as a liquid: [α]D20 = -2.2 (c = 1.00, CHCl3); 1H NMR (300 MHz, CDCl3) δ 4.38-4.30 (m, 1H, CH), 3.58 (t, J = 6.5 Hz, 2H, CH2), 2.46-2.39 (m, 2H, OH + ≡CH), 1.74-1.64 (m, 2H, CH2), 1.55-1.27 (m, 8H, CH2 × 4), 0.87 (s, 9H, CH3 × 3), 0.02 (s, 6H, CH3 × 2); 13C NMR (75 MHz, CDCl3) δ 85.0, 72.7, 63.2, 62.1, 37.5, 32.6, 29.0, 25.9, 25.6, 24.9, 18.3, -5.3; IR (neat) ν (cm−1) 3398, 3312, 2931, 2858, 2115, 1470, 1463, 1388, 1360, 1255, 1100, 1006; MS (ESI) m/z 293 [M + Na]+, 271 [M + H]+; HRMS (ESI) calcd for C15H30NaO2Si+ [M + Na]+: 293.1907, found: 293.1908.

II. Synthesis of optically active propargylic alcohols (R)-1c and (S)-1c a. Synthesis of (R)-1,1-dibromo-8-methoxydec-1-en-9-yne (R)-1c Synthesis of (R)-7-methoxynon-8-yn-1-ol (R)-9 (zj-7-126, 7-129)

Typical Procedure XI: To a dry Schlenk flask were added (R)-8 (4.1179 g, 15.2 mmol) and THF (45 mL) under nitrogen atmosphere. The resulting solution was cooled to 0 °C with an ice bath, and NaH (0.6091 g, 60% dispersion in mineral oil, 15.2 mmol,) was added carefully. After the addition was complete, the resulting mixture was stirred at 0 °C for 1 h. Then the cooling bath was removed and the resulting mixture was stirred for another 1 h followed by the addition of MeI (1.15 mL, d = 0.93 g cm-3, 2.5958 g, 18.29 mmol, 99%) dropwise at 0 °C within 5 min. The

47

resulting mixture was warmed up to room temperature naturally. After 3 h with stirring, the reaction was complete as monitored by TLC. The reaction was quenched with water (5.0 mL) at 0 °C. After separation of the organic layer, the aqueous layer was extracted with Et2O (10 mL × 3). The combined organic layer was washed with brine and dried over anhydrous Na2SO4. After filtration and evaporation, the residue was purified by chromatography [eluent: petroleum ether (60-90 oC)/ethyl acetate = 100/1

(500

mL

× 2)

to

50/1

(500

mL)]

on

silica

gel

to

afford

(R)-tert-butyl((7-methoxynon-8-yn-1-yl)oxy)dimethylsilane (R)-12 as a liquid, which was then submitted to next step without characterization . To a round-bottom flask were added (R)-12 (prepared above) and MeOH (60 mL). Then 3.0 M HCl (1.5 mL) was added. The reaction was complete as monitored by TLC after being stirred at room temperature for 10 h. After evaporation, the residue was purified by chromatography [eluent: petroleum ether (60-90 oC)/ethyl acetate = 10/1 (550 mL) to 5/1 (600 mL) to 3/1 (900 mL)] on silica gel to afford (R)-9 (2.3027 g, 89%, 2 steps) as a liquid: [α]D20 = +57.8 (c = 0.99, CHCl3); 1H NMR (300 MHz, CDCl3) δ 3.94 (td, J1 = 6.5 Hz, J2 = 2.1 Hz, 1H, CH), 3.59 (t, J = 6.6 Hz, 2H, CH2), 3.40 (s, 3H, CH3), 2.80 (bs, 1H, OH), 2.48 (d, J = 2.1 Hz, 1H, ≡CH), 1.78-1.66 (m, 2H, CH2), 1.61-1.30 (m, 8H, CH2 × 4); 13C NMR (75 MHz, CDCl3) δ 82.2, 73.7, 70.7, 62.0, 56.0, 35.0, 32.2, 28.8, 25.3, 24.7; IR (neat) ν (cm−1) 3381, 3295, 2986, 2933, 2859, 2824, 2110, 1464, 1336, 1195, 1109, 1091, 1057; MS (ESI) m/z 193 [M + Na]+, 171 [M + H]+; HRMS (ESI) calcd for C10H18NaO2+ [M + Na]+: 193.1199, found: 193.1200.

Synthesis of (R)-7-methoxynon-8-ynal (R)-10 (zj-7-135)

Typical Procedure XII: To a three-necked flask were added Fe(NO3)3∙9H2O (0.5307 g, 1.29 mmol, 98%), NaCl (0.0751 g, 1.29 mmol), TEMPO (0.2055 g, 1.29

48

mmol, 98%), and DCM (100 mL) subsequently. An oxygen balloon was equipped and then a solution of alcohol (R)-9 (2.1921 g, 12.9 mmol) in 30 mL of DCM was added dropwise via an addition funnel at room temperature within 0.5 h in oxygen atmosphere from the balloon. The resulting mixture was stirred for 16 h until the reaction was complete as monitored by TLC. After filtration through a short column of silica gel [eluent: Et2O (20 mL × 3)] and evaporation, the residue was purified by chromatography [eluent: petroleum ether (60-90 oC)/ethyl acetate = 50/1 (200 mL) to 30/1 (500 mL) to 20/1 (500 mL) to 10/1 (440 mL)] on silica gel to afford (R)-10 (1.5245 g, 70%) as a liquid: [α]D20 = +58.8 (c = 1.00, CHCl3); 1H NMR (300 MHz, CDCl3) δ 9.76 (t, J = 1.5 Hz, 1H, CHO), 3.93 (td, J1 = 6.4 Hz, J2 = 1.7 Hz, 1H, CH), 3.40 (s, 3H, CH3), 2.52-2.40 (m, 3H, ≡CH + CH2), 1.77-1.60 (m, 4H, CH2 × 2), 1.55-1.30 (m, 4H, CH2 × 2);

13

C NMR (75 MHz, CDCl3) δ 202.0, 81.9, 73.4, 70.2,

55.8, 43.0, 34.5, 28.1, 24.1, 21.2; IR (neat) ν (cm−1) 3280, 2986, 2939, 2862, 2824, 2723, 2109, 1724, 1465, 1409, 1391, 1336, 1193, 1156, 1108, 1091; MS (ESI) m/z 191 [M + Na]+; HRMS (ESI) calcd for C10H16NaO2+ [M + Na]+: 191.1043, found: 191.1045. Synthesis of (R)-1,1-dibromo-8-methoxydec-1-en-9-yne (R)-1c (zj-7-137)

Following Typical Procedure VII, the reaction of (R)-10 (1.4345 g, 8.54 mmol)/DCM (90 mL), CBr4 (4.2532 g, 12.81 mmol), and PPh3 (6.8541 g, 25.62 mmol, 98%)/DCM (35 mL) for 70 min afforded (R)-1c (2.5787 g, 93%) [eluent: petroleum ether (60-90 oC)/ethyl acetate = 100/1 (500 mL) to 50/l (500 mL) to 30/l (500 mL)] as a liquid: [α]D20 = +29.5 (c = 1.01, CHCl3); 1H NMR (300 MHz, CDCl3) δ 6.38 (t, J = 7.2 Hz, 1H, =CH), 3.94 (td, J1 = 6.5 Hz, J2 = 2.1 Hz, 1H, CH), 3.42 (s, 3H, CH3), 2.45 (d, J = 2.1 Hz, 1H, ≡CH), 2.10 (q, J = 7.2 Hz, 2H, CH2), 1.77-1.67 (m, 2H, CH2), 1.53-1.27 (m, 6H, CH2 × 3),

13

C NMR (75 MHz, CDCl3) δ 138.7, 88.6, 82.6, 73.8,

70.9, 56.5, 35.3, 32.8, 28.6, 27.6, 24.8; IR (neat) ν (cm−1) 3300, 2986, 2929, 2858, 2822, 2108, 1623, 1461, 1335, 1272, 1197, 1151, 1109; MS (EI) m/z (%) 325 [M

49

(81Br81Br) - H)+, 0.10], 323 [M (79Br81Br) - H)+, 0.18], 321 [M (79Br79Br) - H)+, 0.13], 214 {[M (81Br81Br) - C7H11O]+, 17.78}, 212 {[M (79Br81Br) - C7H11O]+, 33.97}, 210 {[M (79Br79Br) - C7H11O]+, 16.83}, 131 (100); HRMS (EI) calcd for C11H1579Br79BrO [M - H]+: 320.9490, found: 320.9496.

b. Synthesis of (S)-1,1-dibromo-8-methoxydec-1-en-9-yne (S)-1c Synthesis of (S)-7-methoxynon-8-yn-1-ol (S)-9 (zj-7-141, 7-142)

Following Typical Procedure XI, the reaction of (S)-8 (4.0285 g, 14.9 mmol), NaH (0.5970 g, 60% dispersion in mineral oil, 14.9 mmol), MeI (1.13 mL, d = 2.28, 2.5506 g, 17.97 mmol, 99%) afforded (S)-12 [eluent: petroleum ether (60-90 oC)/ethyl acetate = 100/1 (500 mL × 2) to 50/1 (500 mL)] as a liquid, which was then submitted to next step without characterization. The reaction of (S)-12 (prepared above), 3.0 M HCl (1.5 mL), and MeOH (60 mL) for 7 h afforded (S)-9 (2.3743 g, 94%, 2 steps) [eluent: petroleum ether (60-90 o

C)/ethyl acetate = 10/1 (550 mL) to 6/1 (560 mL) to 5/1 (600 mL) to 3/1 (280 mL)]

as a liquid: [α]D20 = -58.1 (c = 0.985, CHCl3); 1H NMR (300 MHz, CDCl3) δ 3.94 (td, J1 = 6.6 Hz, J2 = 1.9 Hz, 1H, CH), 3.59 (t, J = 6.0 Hz, 2H, CH2), 3.41 (s, 3H, CH3), 2.98 (s, 1H, OH), 2.49 (d, J = 2.1 Hz, 1H, ≡CH), 1.78-1.64 (m, 2H, CH2), 1.63-1.29 (m, 8H, CH2 × 4);

13

C NMR (75 MHz, CDCl3) δ 82.3, 73.7, 70.8, 62.3, 56.1, 35.1,

32.3, 28.8, 25.4, 24.8; IR (neat) ν (cm−1) 3393, 3300, 2986, 2934, 2860, 2821, 2109, 1464, 1336, 1194, 1092; MS (ESI) m/z 191 [M + Na]+; HRMS (ESI) calcd for C10H18NaO2+ [M + Na]+: 193.1199, found: 193.1197.

Synthesis of (S)-7-methoxynon-8-ynal (S)-10 (zj-7-143)

50

Following Typical Procedure XII, the reaction of Fe(NO3)3∙9H2O (0.5473 g, 1.33 mmol, 98%), NaCl (0.0771 g, 1.33 mmol), TEMPO (0.2120 g, 1.33 mmol, 98%), DCM (100 mL), and (S)-9 (2.2673 g, 13.3 mmol)/DCM (30 mL) for 16 h afforded (S)-10 (1.4286 g, 64%) [eluent: petroleum ether (60-90 oC)/ethyl acetate = 50/1 (300 mL) to 30/1 (530 mL) to 20/1 (500 mL) to 10/1 (330 mL)] as a liquid: [α]D20 = -59.1 (c = 0.98, CHCl3); 1H NMR (300 MHz, CDCl3) δ 9.76 (t, J = 1.8 Hz, 1H, CHO), 3.94 (td, J1 = 6.5 Hz, J2 = 2.1 Hz, 1H, CH), 3.40 (s, 3H, CH3), 2.50-2.41 (m, 3H, ≡CH + CH2), 1.77-1.59 (m, 4H, CH2 × 2), 1.55-1.30 (m, 4H, CH2 × 2); 13C NMR (75 MHz, CDCl3) δ 202.3, 82.2, 73.7, 70.6, 56.1, 43.4, 34.9, 28.5, 24.5, 21.6; IR (neat) ν (cm−1) 3282, 2985, 2939, 2862, 2824, 2722, 2108, 1724, 1464, 1411, 1391, 1336, 1156, 1108, 1091; MS (ESI) m/z 191 [M + Na]+; HRMS (ESI) calcd for C10H16NaO2+ [M + Na]+: 191.1043, found: 191.1041.

Synthesis of (S)-1,1-dibromo-8-methoxydec-1-en-9-yne (S)-1c (zj-7-146)

Following Typical Procedure VII, the reaction of (S)-10 (1.3286 g, 7.9 mmol)/DCM (90 mL), CBr4 (3.9307 g, 11.85 mmol), and PPh3 (6.3361 g, 23.7 mmol, 98%)/DCM (25 mL) afforded (S)-1c (2.3172 g, 90%) [eluent: petroleum ether (60-90 o

C)/ethyl acetate = 100/1 (500 mL) to 50/l (500 mL) to 30/l (300 mL)] as a liquid:

[α]D20 = -29.2 (c = 0.975, CHCl3); 1H NMR (300 MHz, CDCl3) δ 6.38 (t, J = 7.4 Hz, 1H, =CH), 3.93 (td, J1 = 6.5 Hz, J2 = 1.9 Hz, 1H, CH), 3.41 (s, 3H, CH3), 2.45 (d, J = 2.1 Hz, 1H, ≡CH), 2.10 (q, J = 7.3 Hz, 2H, CH2), 1.77-1.66 (m, 2H, CH2), 1.53-1.28 (m, 6H, CH2 × 3),

13

C NMR (75 MHz, CDCl3) δ 138.6, 88.6, 82.5, 73.8, 70.8, 56.4,

35.2, 32.8, 28.6, 27.6, 24.7; IR (neat) ν (cm−1) 3301, 2986, 2931, 2858, 2822, 2110, 1622, 1463, 1335, 1274, 1196, 1152, 1109; MS (EI) m/z (%) 325 {[M (81Br81Br) - H]+, 0.034}, 323 {[M (79Br81Br) - H]+, 0.069}, 321 {[M (79Br79Br) - H]+, 0.03}, 201 {[M (81Br81Br) - C8H13O]+, 6.70}, 199 {[M (79Br81Br) - C8H13O]+, 14.91}, 197 {[M (79Br79Br) - C8H13O]+, 6.62}, 69 (100); HRMS (EI) calcd for C11H1579Br79BrO [M -

51

H]+: 320.9490, found: 320.9475.

III. Stereodivergent synthesis of xestospongienes E~H. a. Synthesis of (5S,1’E,3’R)-6k, i.e., xestospongiene F (reported as xestospongiene E) Synthesis

of

(Ra,R)-methyl

14,14-dibromo-7-methoxy-4,5,13-tetradecatrienoate

(Ra,R)-4ck (zj-7-138)

Typical Procedure XIII: To a dry Schlenk flask were added CuBr2 (0.1735 g, 0.77 mmol, 99%), (S)-3a (1.4943 g, 5.775 mmol), (R)-1c (1.2481 g, 3.85 mmol)/dioxane (25 mL), and 2k (0.6702 g, 5.775 mmol)/dioxane (13.5 mL) sequentially under nitrogen atmosphere. After continuous stirring for 18 h under reflux at 120 oC, the reaction was complete as monitored by TLC. Then the resulting mixture was cooled down to room temperature. The mixture was diluted with ether (60 mL) and then washed with an aqueous solution of hydrochloric acid (3 M, 10 mL × 3). The organic layer was separated and the aqueous layer was extracted with Et2O (10 mL). The combined organic layer was washed with brine and dried over anhydrous Na2SO4. After filtration and evaporation, the residue was purified via chromatography [eluent: petroleum ether (60-90 oC)/ethyl acetate = 50/1 (500 mL) to 30/1 (510 mL) to 15/1 (480 mL)] on silica gel to afford (Ra,R)-4ck (0.7631 g, 47%, > 99:1 d.r. determined by HPLC analysis) as a liquid: > 99% ee (HPLC conditions: Chiralcel IF column, n-hexane/i-PrOH = 100/1, 1.0 mL/min, λ = 214 nm, tR (major) = 25.9 min); [α]D20 = -21.0 (c = 0.975, CHCl3); 1H NMR (300 MHz, CDCl3) δ 6.39 (t, J = 7.2 Hz, 1H, =CH), 5.29 (q, J = 6.1 Hz, 1H, =CH), 5.05-4.95 (m, 1H, =CH), 3.68 (s, 3H, CH3), 3.58 (q, J = 6.9 Hz, 1H, CH), 3.30 (s, 3H, CH3), 2.48-2.39 (m, 2H, CH2), 2.38-2.28 (m, 2H, CH2), 2.10 (q, J = 7.2 Hz, 2H, CH2), 1.70-1.25 (m, 8H, CH2 × 4); 13

C NMR (75 MHz, CDCl3) δ 204.2, 173.1, 138.6, 93.3, 90.3, 88.5, 80.2, 56.0, 51.5,

52

35.5, 33.0, 32.8, 28.8, 27.6, 25.1, 23.6; IR (neat) ν (cm−1) 2978, 2931, 2857, 2819, 1963, 1739, 1624, 1436, 1362, 1343, 1253, 1198, 1161, 1087; MS (ESI) m/z 449 [M (81Br81Br) + Na]+, 447 [M (79Br81Br) + Na]+, 445 [M (79Br79Br) + Na]+, HRMS (ESI) calcd for C16H2479Br79Br NaO3+ [(M (79Br79Br) + Na]+: 444.9984, found: 444.9989.

Synthesis of (Ra,R)-14,14-dibromo-7-methoxy-4,5,13-tetradecatrienoic acid (Ra,R)-5k (zj-7-144)

Following Typical Procedure II, the reaction of (Ra,R)-4ck (0.6801 g, 1.6 mmol), EtOH/H2O = 1:1 by volume (pre-mixed by using 8 mL of H2O and 8 mL of EtOH), and LiOH·H2O (0.1063 g, 2.4 mmol) at 90 oC for 1.5 h afforded (Ra,R)-5k (0.6017 g, 92%) [eluent: petroleum ether (60-90 oC)/ethyl acetate = 10/1 (550 mL) to 8/1 (540 mL) to 5/1 (600 mL)] as an oil: [α]D20 = -20.2 (c = 1.00, CHCl3); 1H NMR (300 MHz, CDCl3) δ 9.68 (bs, 1H, COOH), 6.39 (t, J = 7.4 Hz, 1H, =CH), 5.30 (q, J = 6.1 Hz, 1H, =CH), 5.07-4.98 (m, 1H, =CH), 3.60 (q, J1 = 7.0 Hz, 1H, CH), 3.31 (s, 3H, CH3), 2.54-2.44 (m, 2H, CH2), 2.39-2.29 (m, 2H, CH2), 2.10 (q, J = 7.2 Hz, 2H, CH2), 1.71-1.22 (m, 8H, CH2 × 4); 13C NMR (75 MHz, CDCl3) δ 204.3, 178.9, 138.8, 93.5, 90.2, 88.6, 80.4, 56.0, 35.5, 33.1, 32.9, 28.9, 27.7, 25.2, 23.4; IR (neat) ν (cm−1) 3752-2188 (COOH), 2978, 2933, 2858, 2822, 2660, 1964, 1713, 1624, 1435, 1336, 1278, 1251, 1208, 1157, 1109, 1086; MS (ESI) m/z 435 [M (81Br81Br) + Na]+, 433 [M (81Br79Br) + Na]+, 431 [M (79Br79Br) + Na]+; HRMS (ESI) calcd. for C15H2279Br79BrNaO3+ [M (79Br79Br) + Na] +: 430.9828, found: 430.9830.

Synthesis of (5S)-(10’,10’-dibromo-3’(R)-methoxy-1’(E),9’-decadien-1’-yl)dihydro2(3H)-furanone (5S,1’E,3’R)-6k, i.e., xestospongiene F (reported as xestospongiene E) (zj-7-188)

53

Following Typical Procedure VIII, the reaction of AgOTs (0.0285 g, 0.1 mmol, 98%), Au(LB-Phos)Cl (0.0597 g, 0.1 mmol), CHCl3 (5 mL), and (Ra,R)-5k (0.4096 g, 1.0 mmol)/CHCl3 (5 mL) at -30 oC for 24 h afforded (5S,1’E,3’R)-6k,20 i.e., xestospongiene F [(0.3844 g, 94%, (5S,1’E,3’R)/(5R,1’Z,3’R) = 98:2 (determined by 1

H NMR) and > 99:1 d.r. (determined by SFC analysis)] [eluent: petroleum ether

(60-90 oC)/ethyl acetate/dichloromethane = 150/10/1 (480 mL) to 100/10/1 (550 mL) to 80/10/1 (540 mL × 3)] ((5S,1’E,3’R)/(5R,1’Z,3’R) = 97:3 determined by 1H NMR of crude product) as a liquid: > 99% ee (SFC: Chiralcel AD-H column, n-hexane/i-PrOH = 97/3, 1.3 mL/min, λ = 214 nm, tR (major) = 15.8 min); [α]D20 = +21.9 (c = 1.01, CHCl3); [α]D20 = +27.3 (c = 0.38, MeOH); (Lit.20 [α]D20 = -44.3 (c = 0.5, MeOH)); 1H NMR (300 MHz, CDCl3) δ 6.39 (t, J = 7.4 Hz, 1H, =CH), 5.82-5.58 (m, 2H, =CH × 2), 4.98 (q, J = 6.6 Hz, 1H, CH), 3.58 (q, J = 6.2 Hz, 1H, CH), 3.27 (s, 3H, CH3), 2.64-2.39 (m, 3H, CH2 + one proton of CH2), 2.15-1.94 (m, 3H, CH2 + one proton of CH2), 1.66-1.20 (m, 8H, CH2 × 4); the following signals are discernible for (5R,1’Z,3’R)-6k: δ 5.56-5.47 (m, 1H, =CH), 5.35-5.25 (m, 1H, CH);

13

C NMR (75

MHz, CDCl3) δ 176.6, 138.5, 134.1, 129.4, 88.2, 80.8, 79.7, 56.1, 34.8, 32.6, 28.6, 28.5, 28.2, 27.3, 24.6; IR (neat) ν (cm−1) 2974, 2931, 2857, 2817, 1777, 1460, 1421, 1326, 1296, 1214, 1176, 1112, 1091, 1012; MS (ESI) m/z 413 [M (81Br81Br) + H]+,.411 [M (79Br81Br) + H]+, 409 [M (79Br79Br) + H]+.

b. Synthesis of xestospongiene G Synthesis

of

(Sa,R)-methyl

14,14-dibromo-7-methoxy-4,5,13-tetradecatrienoate

(Sa,R)-4ck (zj-7-139)

54

Following Typical Procedure XIII, the reaction of CuBr2 (0.1736 g, 0.77 mmol, 99%), (R)-3a (1.4942 g, 5.775 mmol, 98%), (R)-1c (1.2469 g, 3.85 mmol)/dioxane (25 mL), and 2k (0.6702 g, 5.775 mmol)/dioxane (13.5 mL) at 120 oC for 18 h afforded (Sa,R)-4ck (0.7035 g, 43%, > 99:1 d.r. by HPLC analysis) [eluent: petroleum ether (60-90 oC)/ethyl acetate = 50/1 (500 mL) to 30/1 (510 mL) to 15/1 (480 mL)] as a liquid: > 99% ee, > 99:1 d.r. (HPLC conditions: Chiralcel IF column, n-hexane/i-PrOH = 100/1, 1.0 mL/min, λ = 214 nm, tR (major) = 36.6 min, tR (minor) = 25.6 min); [α]D20 = +72.2 (c = 1.025, CHCl3); 1H NMR (300 MHz, CDCl3) δ 6.38 (t, J = 7.4 Hz, 1H, =CH), 5.23 (q, J = 6.7 Hz, 1H, =CH), 5.04-4.94 (m, 1H, =CH), 3.68 (s, 3H, CH3), 3.58 (q, J = 6.9 Hz, 1H, CH), 3.32 (s, 3H, CH3), 2.51-2.43 (m, 2H, CH2), 2.40-2.31 (m, 2H, CH2), 2.09 (q, J = 7.2 Hz, 2H, CH2), 1.69-1.23 (m, 8H, CH2 × 4); 13

C NMR (75 MHz, CDCl3) δ 204.1, 173.1, 138.7, 93.3, 90.2, 88.5, 80.2, 56.0, 51.5,

35.6, 33.1, 32.8, 28.8, 27.6, 25.0, 23.8; IR (neat) ν (cm−1) 2978, 2931, 2857, 2819, 1963, 1738, 1622, 1463, 1435, 1417, 1362, 1343, 1254, 1227, 1197, 1161, 1087, 1023; MS (ESI) m/z 449 [M (81Br81Br) + Na]+, 447 [M (79Br81Br) + Na]+, 445 [M (79Br79Br) + Na]+; HRMS (ESI) calcd for C16H2479Br79BrNaO3+ [M (79Br79Br) + Na]+: 444.9984, found: 444.9965.

Synthesis of (Sa,R)-14,14-dibromo-7-methoxy-4,5,13-tetradecatrienoic acid (Sa,R)-5k (zj-7-145)

Following Typical Procedure II, the reaction of (Sa,R)-4ck (0.6031 g, 1.42 mmol), EtOH/H2O = 1:1 by volume (pre-mixed by using 7 mL of H2O and 7 mL of

55

EtOH), and LiOH∙H2O (0.0945 g, 2.13 mmol, 95%) at 90 oC for 1.5 h afforded (Sa,R)-5k (0.5272 g, 90%) [eluent: petroleum ether (60-90 oC)/ethyl acetate = 10/1 (550 mL) to 8/1 (540 mL) to 5/1 (600 mL)] as an oil: [α]D20 = +72.3 (c = 1.00, CHCl3); 1

H NMR (300 MHz, CDCl3) δ 9.72 (bs, 1H, COOH), 6.38 (t, J = 7.1 Hz, 1H, =CH),

5.25 (q, J = 6.0 Hz, 1H, =CH), 5.06-4.97 (m, 1H, =CH), 3.60 (q, J = 6.9 Hz, 1H, CH), 3.33 (s, 3H, CH3), 2.52 (t, J = 7.1 Hz, 2H, CH2), 2.41-2.31 (m, 2H, CH2), 2.09 (q, J = 7.3 Hz, 2H, CH2), 1.70-1.22 (m, 8H, CH2 × 4); 13C NMR (75 MHz, CDCl3) δ 204.2, 178.8, 138.7, 93.5, 90.2, 88.5, 80.3, 56.1, 35.6, 33.2, 32.8, 28.8, 27.7, 25.0, 23.6; IR (neat) ν (cm−1) 3618-2182 (COOH), 2978, 2933, 2858, 2820, 2658, 1964, 1712, 1435, 1334, 1250, 1205, 1156, 1109, 1086; MS (ESI) m/z 435 [M (81Br81Br) + Na]+, 433 [M (81Br79Br) + Na]+, 431 [M (79Br79Br) + Na]+; HRMS (ESI) calcd. for C15H2279Br79Br NaO3+ [M(79Br79Br) + Na]+: 430.9828, found: 430.9832.

Synthesis of (5R)-(10’,10’-dibromo-3’(R)-methoxy-1’(E),9’-decadien-1’-yl) dihydro -2(3H)-furanone xestospongiene G (zj-8-012)

Following Typical Procedure VIII, the reaction of AgOTs (0.0285 g, 0.1 mmol, 98%), Au(LB-Phos)Cl (0.0598 g, 0.1 mmol), CHCl3 (5 mL), and (Sa,R)-5k (0.4097 g, 1.0 mmol)/CHCl3 (5 mL) at -30 oC for 24 h afforded xestospongiene G20 (0.3791 g, 93%, E only, > 99:1 d.r. determined by SFC analysis) [eluent: petroleum ether (60-90 o

C)/ethyl acetate/dichloromethane = 150/10/1 (480 mL) to 70/7/1 (550 mL) to 40/5/1

(540 mL) to 24/3/1 (540 mL)] ((5R,1’E,3’R)/(5S,1’Z,3’R) = 97:3 determined by 1H NMR of crude product) as an oil: > 99% ee (SFC: Chiralcel AD-H column, n-hexane/i-PrOH = 9/1, 2.0 mL/min, λ = 214 nm, tR (major) = 16.2 min); [α]D20 = -3.4 (c = 0.98, CHCl3); [α]D20 = -7.1 (c = 0.545, MeOH); (Lit.20 [α]D20 = -10.5 (c = 0.5, MeOH)); 1H NMR (300 MHz, CDCl3) δ 6.38 (t, J = 7.2 Hz, 1H, =CH), 5.77-5.60 (m, 2H, =CH × 2), 4.98 (q, J = 6.5 Hz, 1H, CH), 3.57 (q, J = 6.3 Hz, 1H, CH), 3.27 (s, 3H,

56

CH3), 2.61-2.37 (m, 3H, CH2 + one proton of CH2), 2.14-1.94 (m, 3H, CH2 + one proton of CH2), 1.64-1.22 (m, 8H, CH2 × 4);

13

C NMR (75 MHz, CDCl3) δ 176.5,

138.5, 133.9, 129.7, 88.2, 80.7, 79.6, 56.1, 34.7, 32.5, 28.5, 28.4, 28.1, 27.3, 24.5; IR (neat) ν (cm−1) 2976, 2932, 2857, 2820, 1778, 1461, 1420, 1325, 1296, 1214, 1177, 1108, 1092, 1012; MS (ESI): m/z 413 [M (81Br81Br) + H]+, 411 [M (79Br81Br) + H]+, 409 [M (79Br79Br) + H]+.

c. Synthesis of xestospongiene H Synthesis

of

(Ra,S)-methyl

14,14-dibromo-7-methoxy-4,5,13-tetradecatrienoate

(Ra,S)-4ck (zj-7-148)

Typical Procedure XIV (three reactions in parallel): To a dry Schlenk flask were added CuBr2 (0.0510 g, 0.226 mmol, 99%), (S)-3a (0.4380 g, 1.695 mmol, 98%), (S)-1c (0.3629 g, 1.13 mmol)/dioxane (8.3 mL), and 2k (0.1970 g, 1.695 mmol)/dioxane (3 mL) sequentially under nitrogen atmosphere; to another dry Schlenk flask were added CuBr2 (0.0508 g, 0.226 mmol, 99%), (S)-3a (0.4369 g, 1.695 mmol), (S)-1c (0.3651 g, 1.13 mmol, 98%)/dioxane (8.3 mL), and 2k (0.1961 g, 1.695 mmol)/dioxane (3 mL) sequentially under nitrogen atmosphere; to the third dry Schlenk flask were added CuBr2 (0.0508 g, 0.226 mmol, 99%), (S)-3a (0.4368 g, 1.695 mmol, 98%), (S)-1c (0.3667 g, 1.13 mmol)/dioxane (8.3 mL), and 2k (0.1971 g, 1.695 mmol)/dioxane (3 mL) sequentially under nitrogen atmosphere; the three reactions were conducted separately. After continuous stirring for 18 h at 120 oC, the reactions were complete as monitored by TLC. After cooling down to room temperature, the three resulting mixtures were combined and diluted with ether (60 mL), then washed with an aqueous solution of hydrochloric acid (3 M, 10 mL × 3). The organic layer was separated and the aqueous layer was extracted with Et2O (10 mL). The combined organic layer was washed with brine and dried over anhydrous

57

Na2SO4. After filtration and evaporation, the residue was purified by chromatography [eluent: petroleum ether (60-90 oC)/ethyl acetate = 50/1 (500 mL) to 30/1 (500 mL) to 20/1 (500 mL)] on silica gel to afford (Ra,S)-4ck (0.8064 g, 60%, 99:1 d.r. determined by 1H NMR and HPLC analysis) as a liquid: > 99% ee (HPLC conditions: Chiralcel IF column, n-hexane/i-PrOH = 100/1, 1.0 mL/min, λ = 214 nm, tR (major) = 25.7 min , tR (minor) = 37.9 min); [α]D20 = -71.9 (c = 1.025, CHCl3); 1H NMR (300 MHz, CDCl3) δ 6.38 (t, J = 7.4 Hz, 1H, =CH), 5.24 (q, J = 6.5 Hz, 1H, =CH), 5.04-4.95 (m, 1H, =CH), 3.68 (s, 3H, CH3), 3.58 (q, J = 6.9 Hz, 1H, CH), 3.32 (s, 3H, CH3), 2.53-2.42 (m, 2H, CH2), 2.41-2.30 (m, 2H, CH2), 2.09 (q, J = 7.2 Hz, 2H, CH2), 1.69-1.24 (m, 8H, CH2 × 4);

13

C NMR (75 MHz, CDCl3) δ 204.1, 173.1, 138.7, 93.3, 90.2, 88.5,

80.2, 56.0, 51.5, 35.6, 33.1, 32.8, 28.8, 27.6, 25.0, 23.8; IR (neat) ν (cm−1) 2977, 2931, 2857, 2818, 1963, 1740, 1436, 1363, 1250, 1198, 1161, 1109, 1087; MS (ESI) m/z 449 [M (81Br81Br) + Na]+, 447 [M (79Br81Br) + Na]+, 445 [M (79Br79Br) + Na]+; HRMS (ESI) calcd for C16H2479Br79Br NaO3+ [M (79Br79Br) + Na]+: 444.9984, found: 444.9976. Synthesis of (Ra,S)-14,14-dibromo-7-methoxy-4,5,13-tetradecatrienoic acid (Ra,S)-5k (zj-7-151)

Following Typical Procedure II, the reaction of (Ra,S)-4ck (0.6664 g, 1.57 mmol), EtOH/H2O = 1:1 by volume (pre-mixed by using 8 mL of H2O and 8 mL of EtOH), and LiOH∙H2O (0.1047 g, 2.355 mmol) at 90 oC for 1.5 h afforded (Ra,S)-5k (0.6102 g, 95%) [eluent: petroleum ether (60-90 oC)/ethyl acetate = 10/1 (550 mL) to 8/1 (540 mL) to 5/1 (600 mL)] as a liquid: [α]D20 = -72.2 (c = 1.01, CHCl3); 1H NMR (300 MHz, CDCl3) δ 1H NMR (300 MHz, CDCl3) δ 10.73 (bs, 1H, COOH), 6.38 (t, J = 7.4 Hz, 1H, =CH), 5.25 (q, J = 6.2 Hz, 1H, =CH), 5.07-4.97 (m, 1H, =CH), 3.60 (q, J = 6.6 Hz, 1H, CH), 3.33 (s, 3H, CH3), 2.57-2.46 (m, 2H, CH2), 2.42-2.30 (m, 2H, CH2), 2.09 (q, J = 7.2 Hz, 2H, CH2), 1.70-1.23 (m, 8H, CH2 × 4);

58

13

C NMR (75 MHz,

CDCl3) δ 204.1, 178.8, 138.7, 93.4, 90.1, 88.5, 80.3, 56.0, 35.5, 33.1, 32.8, 28.7, 27.6, 25.0, 23.5; IR (neat) ν (cm−1) 3693-2185 (COOH), 2976, 2933, 2858, 2820, 2664, 1963, 1712, 1435, 1335, 1251, 1206, 1156, 1108, 1086; MS (ESI) m/z 435 [M (81Br81Br) + Na]+, 433 [M (79Br81Br) + Na]+, 431 [M (79Br79Br) + Na]+; HRMS (ESI) calcd. for C15H2279Br79Br NaO3+ [M (79Br79Br) + Na]+: 430.9828, found: 430.9821.

Synthesis of (5S)-(10’,10’-dibromo-3’(S)-methoxy-1’(E),9’-decadien-1’-yl)dihydro2(3H)-furanone xestospongiene H (zj-8-013)

Following Typical Procedure VIII, the reaction of AgOTs (0.0285 g, 0.1 mmol, 98%), Au(LB-Phos)Cl (0.0597 g, 0.1 mmol), CHCl3 (5 mL), and (Ra,S)-5k (0.4101 g, 1.0 mmol)/CHCl3 (5 mL) at -30 oC for 24 h afforded xestospongiene H20 (0.3766 g, 92%, E only, > 99:1 d.r. determined by SFC analysis) [eluent: petroleum ether (60-90 o

C)/ethyl acetate/dichloromethane = 150/10/1 (480 mL) to 70/7/1 (550 mL) to 40/5/1

(540 mL) to 24/3/1 (540 mL)] ((5S,1’E,3’S)/(5R,1’Z,3’S) = 97:3 determined by 1H NMR of crude product) as an oil: > 99% ee, > 99:1 d.r. (SFC: Chiralcel AD-H column, n-hexane/i-PrOH = 9/1, 2.0 mL/min, λ = 214 nm, tR (major) = 9.4 min); [α]D20 = +3.5 (c = 0.995, CHCl3); [α]D20 = +7.0 (c = 0.49, MeOH); (Lit.20 [α]D20 = +11.0 (c = 0.5, MeOH)); 1H NMR (300 MHz, CDCl3) δ 6.39 (t, J = 7.2 Hz, 1H, =CH), 5.78-5.58 (m,

2H, =CH × 2), 4.98 (q, J = 6.8 Hz, 1H, CH), 3.57 (q, J = 6.4 Hz, 1H, CH), 3.26 (s, 3H, CH3), 2.60-2.37 (m, 3H, CH2 + one proton of CH2), 2.14-1.93 (m, 3H, CH2 + one proton of CH2), 1.66-1.19 (m, 8H, CH2 × 4);

13

C NMR (75 MHz, CDCl3) δ 176.4,

138.4, 133.8, 129.6, 88.1, 80.7, 79.5, 56.0, 34.7, 32.5, 28.5, 28.4, 28.1, 27.3, 24.5; IR (neat) ν (cm−1) 2978, 2932, 2857, 2821, 1778, 1461, 1420, 1326, 1296, 1215, 1177, 1108, 1093, 1012; MS (ESI): m/z 413 [M (81Br81Br) + H]+, 411 [M (79Br81Br) + H]+, 409 [M (79Br79Br) + H]+.

59

d. Synthesis of (5R,1’E,3’S)-6k, i.e., xestospongiene E (reported as xestospongiene F) Synthesis

of

(Sa,S)-methyl

14,14-dibromo-7-methoxy-4,5,13-tetradecatrienoate

(Sa,S)-4ck (zj-7-150)

To a dry Schlenk flask were added CuBr2 (0.1540 g, 0.682 mmol, 99%), (R)-3a (1.4957 g, 5.797 mmol, 98%), (S)-1c (1.1058 g, 3.41 mmol)/dioxane (20 mL), and 2k (0.6740 g, 5.797 mmol)/dioxane (14 mL) sequentially under nitrogen atmosphere. After continuous stirring for 18 h at 120 oC, the reaction was complete as monitored by TLC. Then the resulting mixture was cooled down to room temperature, diluted with ether (60 mL), and washed with an aqueous solution of hydrochloric acid (3 M, 10 mL × 3). The organic layer was separated and the aqueous layer was extracted with Et2O (10 mL). The combined organic layer was washed with brine and dried over anhydrous Na2SO4. After filtration and evaporation, the residue was purified by chromatography [eluent: petroleum ether (60-90 oC)/ethyl acetate = 50/1 (500 mL) to 30/1 (500 mL) to 20/1 (500 mL)] on silica gel to afford (Sa,S)-4ck (0.7177 g, 50%, > 99:1 d.r. determined by 1H NMR and HPLC analysis) as a liquid: > 99% ee, > 99:1 d.r. (HPLC conditions: Chiralcel IF column, n-hexane/i-PrOH = 100/1, 1.0 mL/min, λ = 214 nm, tR (major) = 14.8 min, tR (minor) = 13.5 min); [α]D20 = +21.2 (c = 0.98, CHCl3); δ 6.39 (t, J = 7.2 Hz, 1H, =CH), 5.28 (q, J = 6.2 Hz, 1H, =CH), 5.04-4.95 (m, 1H, =CH), 3.68 (s, 3H, CH3), 3.58 (q, J = 6.9 Hz, 1H, CH), 3.30 (s, 3H, CH3), 2.47-2.39 (m, 2H, CH2), 2.38-2.28 (m, 2H, CH2), 2.10 (q, J = 7.3 Hz, 2H, CH2), 1.70-1.25 (m, 8H, CH2 × 4); 13C NMR (75 MHz, CDCl3) δ 204.1, 173.1, 138.7, 93.3, 90.3, 88.5, 80.2, 55.9, 51.5, 35.5, 33.0, 32.8, 28.8, 27.6, 25.0, 23.6; IR (neat) ν (cm−1) 2981, 2931, 2857, 2819, 1963, 1740, 1436, 1363, 1254, 1198, 1161, 1109, 1087; MS (ESI) m/z 449 [M (81Br81Br) + Na]+, 447 [M (79Br81Br) + Na]+, 445 [M (79Br79Br) + Na]+; HRMS (ESI) calcd for C16H2479Br79BrNaO3+ [M (79Br79Br) + Na]+: 444.9984,

60

found: 444.9969.

Synthesis of (Sa,S)-14,14-dibromo-7-methoxy-4,5,13-tetradecatrienoic acid (Sa,S)-5k (zj-7-156)

Following Typical Procedure II, the reaction of (Sa,S)-4ck (0.6575 g, 1.55 mmol), EtOH/H2O = 1:1 by volume (pre-mixed by using 8 mL of H2O and 8 mL of EtOH), and LiOH∙H2O (0.1031 g, 2.325 mmol) at 90 oC for 1.5 h afforded (Sa,S)-5k (0.6022 g, 95%) [eluent: petroleum ether (60-90 oC)/ethyl acetate = 10/1 (550 mL) to 8/1 (540 mL) to 5/1 (360 mL)] as an oil: [α]D20 = +19.9 (c = 0.975, CHCl3); 1H NMR (300 MHz, CDCl3) δ 10.12 (bs, 1H, COOH), 6.39 (t, J = 7.2 Hz, 1H, =CH), 5.30 (q, J = 6.1 Hz, 1H, =CH), 5.07-4.98 (m, 1H, =CH), 3.61 (q, J = 7.0 Hz, 1H, CH), 3.31 (s, 3H, CH3), 2.49 (t, J = 7.5 Hz, 2H, CH2), 2.40-2.29 (m, 2H, CH2), 2.10 (q, J = 7.2 Hz, 2H, CH2), 1.71-1.24 (m, 8H, CH2 × 4);

13

C NMR (75 MHz, CDCl3) δ 204.3, 178.9,

138.7, 93.5, 90.2, 88.5, 80.3, 56.0, 35.5, 33.1, 32.9, 28.9, 27.7, 25.1, 23.3; IR (neat) ν (cm−1) 3031-3031 (COOH), 2928, 2856, 2662, 1964, 1713, 1417, 1338, 1257, 1202, 1157, 1108, 1084; MS (ESI) m/z 435 [M (81Br81Br) + Na]+, 433 [M (79Br81Br) + Na]+, 431 [M (79Br79Br) + Na]+; HRMS (ESI) calcd. for C15H2279Br79Br NaO3

+

[M

(79Br79Br) + Na]+: 430.9828, found: 430.9825.

Synthesis of (5R)-(10’,10’-dibromo-3’(S)-methoxy-1’(E),9’-decadien-1’-yl)dihydro2(3H)-furanone (5R,1’E,3’S)-6k, i.e., xestospongiene E (reported as xestospongiene F) (zj-7-189)

61

Following Typical Procedure VIII, the reaction of AgOTs (0.0285 g, 0.1 mmol, 98%), Au(LB-Phos)Cl (0.0597 g, 0.1 mmol), CHCl3 (5 mL), and (Sa,S)-5k (0.4102 g, 1.0 mmol)/CHCl3 (5 mL) at -30 oC for 24.5 h afforded (5R,1’E,3’S)-6k,20 i.e., xestospongiene E (0.3851 g, 94%, (5R,1’E,3’S)/(5S,1’Z,3’S) = 99:1 determined by 1H NMR, > 99:1 d.r. determined by SFC analysis) [eluent: petroleum ether (60-90 o

C)/ethyl acetate/dichloromethane = 150/10/1 (480 mL) to 100/10/1 (550 mL) to

80/10/1 (540 mL × 3)] ((5R,1’E,3’S)/(5S,1’Z,3’S) = 97:3 determined by 1H NMR of crude product) as an oil: > 99% ee (SFC: Chiralcel AD-H column, n-hexane/i-PrOH = 9/1, 2.0 mL/min, λ = 214 nm, tR (major) = 21.0 min, tR (minor) = 11.6 min); [α]D20 = -22.3 (c = 1.00, CHCl3); [α]D20 = -27.4 (c = 0.495, MeOH); (Lit.20 [α]D20 = +45.6 (c = 0.4, MeOH)); 1H NMR (300 MHz, CDCl3) δ 6.39 (t, J = 7.2 Hz, 1H, =CH), 5.79-5.59 (m, 2H, =CH × 2), 4.98 (q, J = 6.6 Hz, 1H, CH), 3.58 (q, J = 6.1 Hz, 1H, CH), 3.27 (s, 3H, CH3), 2.62-2.38 (m, 3H, CH2 + one proton of CH2), 2.15-1.94 (m, 3H, CH2 + one proton of CH2), 1.67-1.16 (m, 8H, CH2 × 4); the following signals are discernible for (5S,1’Z,3’S)-6k: δ 5.56-5.48 (m, 1H, =CH), 5.35-5.25 (m, 1H, CH);

13

C NMR (75

MHz, CDCl3) δ 176.6, 138.5, 134.1, 129.5, 88.3, 80.8, 79.7, 56.2, 34.8, 32.6, 28.6, 28.5, 28.2, 27.4, 24.6; IR (neat) ν (cm−1) 2977, 2931, 2857, 2821, 1777, 1460, 1421, 1326, 1296, 1215, 1176, 1112, 1091, 1012; MS (ESI): m/z 413 [M (81Br81Br) + H]+, 411 [M (79Br81Br) + H]+, 409 [M (79Br79Br) + H]+.

e. Gram scale synthesis of (5S,1’E,3’R)-6k , i.e., xestospongiene F) Synthesis

of

(Ra,R)-methyl

14,14-dibromo-7-methoxy-4,5,13-tetradecatrienoate

(Ra,R)-4ck (zj-7-177)

62

Following Typical Procedure XIV (four reactions in parallel), the reaction of CuBr2 (0.0676 g, 0.3 mmol, 99%), (S)-3a (0.5803 g, 2.25 mmol, 98%), (R)-1c (0.4862 g, 1.5 mmol)/dioxane (8 mL), and 2k (0.2609 g, 2.25 mmol) in dioxane/(5 mL) at 120 o

C for 18 h; the reaction of CuBr2 (0.0677 g, 0.3 mmol, 99%), (S)-3a (0.5804 g, 2.25

mmol, 98%), (R)-1c (0.4860 g, 1.5 mmol)/dioxane (8 mL), and 2k (0.2620 g, 2.25 mmol)/dioxane (5 mL) at 120 oC for 18 h; the reaction of CuBr2 (0.0677 g, 0.3 mmol, 99%), (S)-3a (0.5810 g, 2.25 mmol, 98%), (R)-1c (0.4859 g, 1.5 mmol)/dioxane (8 mL), and 2k (0.2614 g, 2.25 mmol)/dioxane (5 mL) at 120 oC for 18 h; the reaction of CuBr2 (0.0675 g, 0.3 mmol, 99%), (S)-3a (0.5810 g, 2.25 mmol, 98%), (R)-1c (0.4863 g, 1.5 mmol)/dioxane (8 mL), and 2k (0.2613 g, 2.25 mmol)/dioxane (5 mL) at 120 o

C for 18 h. The four reactions together afforded (Ra,R)-4ck (1.4779 g, 58%, > 99:1

d.r. determined by 1H NMR and HPLC analysis) [eluent: petroleum ether (60-90 o

C)/ethyl acetate = 50/1 (500 mL) to 30/1 (500 mL) to 20/1 (500 mL)] as a liquid: >

99% ee (HPLC conditions: Chiralcel IF column, n-hexane/i-PrOH = 100/1, 1.0 mL/min, λ = 214 nm, tR (major) = 14.0 min, tR (minor) = 15.0 min), [α]D20 = -21.1 (c = 0.98, CHCl3); 1H NMR (300 MHz, CDCl3) δ 6.39 (t, J = 7.2 Hz, 1H, =CH), 5.29 (q, J = 6.1 Hz, 1H, CH),5.04-4.95 (m, 1H, =CH), 3.68 (s, 3H, CH3), 3.58 (q, J = 6.7 Hz, 1H, CH),, 3.30 (s, 3H, CH3), 2.48-2.40 (m, 2H, CH2), 2.38-2.28 (m, 2H, CH2), 2.10 (q, J = 7.3 Hz, 2H, CH2), 1.69-1.25 (m, 8H, CH2 × 4);

13

C NMR (75 MHz, CDCl3) δ

204.2, 173.2, 138.7, 93.3, 90.3, 88.5, 80.2, 56.0, 51.5, 35.6, 33.1, 32.8, 28.8, 27.6, 25.1, 23.6.

Synthesis of (Ra,R)-14,14-dibromo-7-methoxy-4,5,13-tetradecatrienoic acid (Ra,R)-5k (zj-7-182)

63

To a round-bottom flask were added (Ra,R)-4ck (1.2704 g, 3.0 mmol), EtOH/H2O = 1:1 by volume (pre-mixed by using 15 mL of H2O and 15 mL of EtOH) and LiOH∙H2O (0.1460 g, 3.3 mmol, 95%) sequentially. After stirring for 1 h under reflux at 90 oC, the reaction was complete as monitored by TLC. Then the mixture was cooled down to room temperature. After evaporation to remove EtOH, the aqueous layer was acidified with an aqueous solution of hydrochloric acid (aq., 3.0 M) until pH = 1. The aqueous layer was then extracted with Et2O (30 mL × 3). The combined organic layer was washed with brine and dried over anhydrous Na2SO4, filtration, evaporation, and column chromatography on silica gel to afford (Ra,R)-5k (1.1945 g, 97%) [eluent: petroleum ether (60-90 oC)/ethyl acetate = 10/1 (550 mL) to 8/1 (540 mL) to 5/1 (600 mL)] as an oil: [α]D20 = -20.6 (c = 1.01, CHCl3); 1H NMR (300 MHz, CDCl3) δ 10.37 (bs, 1H, COOH), 6.39 (t, J = 7.4 Hz, 1H, =CH), 5.30 (q, J = 6.1 Hz, 1H, =CH), 5.07-4.98 (m, 1H, =CH), 3.60 (q, J = 6.7 Hz, 1H, CH), 3.31 (s, 3H, CH3), 2.53-2.44 (m, 2H, CH2), 2.39-2.28 (m, 2H, CH2), 2.09 (q, J = 7.2 Hz, 2H, CH2), 1.71-1.25 (m, 8H, CH2 × 4); 13C NMR (75 MHz, CDCl3) δ 204.3, 178.9, 138.7, 93.4, 90.2, 88.5, 80.3, 56.0, 35.5, 33.1, 32.9, 28.8, 27.6, 25.1, 23.3.

Gram scale Synthesis of (5S)-(10’,10’-dibromo-3’(R)-methoxy-1’(E),9’-decadien1’-yl)dihydro-2(3H)-furanone (5S,1’E,3’R)-6k, xestospongiene F (zj-8-011)

Following Typical Procedure VIII, the reaction of AgOTs (0.077 g, 0.27 mmol), Au(LB-Phos)Cl (0.1613 g, 0.27 mmol), CHCl3 (17 mL), and (Ra,R)-5k (1.1054 g, 2.7

64

mmol)/CHCl3 (10 mL) at -30 oC for 24 h afforded impure (5S,1’E,3’R)-6k20 (1.0795 g) [eluent: petroleum ether (60-90 oC)/ethyl acetate/dichloromethane = 150/10/1 (480 mL) to 100/10/1 (550 mL) to 80/10/1 (540 mL × 3)] as an oil, which was then further purified

by

chromatography

[eluent:

petroleum

ether

(60-90

o

C)/ethyl

acetate/dichloromethane = 150/10/1 (480 mL) to 70/7/1 (550 mL) to 40/5/1 (540 mL) to 24/3/1 (540 mL) to 16/2/1 (540 mL)] to give (5S,1’E,3’R)-6k, xestospongiene F (1.0371 g, 94%, (5S,1’E,3’R)/(5R,1’Z,3’R) = 98:2 determined by 1H NMR analysis, d.r. = 98:2 determined by SFC analysis) ((5S,1’E,3’R)/(5R,1’Z,3’R) = 97:3 determined by 1H NMR of crude product) as an oil: 99% ee (SFC: Chiralcel AD-H column, n-hexane/i-PrOH = 9/1, 2.0 mL/min, λ = 214 nm, tR (major) = 11.0 min, tR (minor) = 21.8 min); [α]D20 = +21.5 (c = 1.00, CHCl3); [α]D20 = +27.4 (c = 0.43, MeOH); (Lit.20 [α]D20 = -44.3 (c = 0.5, MeOH)); 1H NMR (300 MHz, CDCl3) δ 6.39 (t, J = 7.4 Hz, 1H, =CH), 5.84-5.57 (m, 2H, =CH × 2), 4.98 (q, J = 6.7 Hz, 1H, CH), 3.58 (q, J = 6.1 Hz, 1H, CH), 3.26 (s, 3H, CH3), 2.62-2.37 (m, 3H, CH2 + one proton of CH2), 2.15-1.94 (m, 3H, CH2 + one proton of CH2), 1.66-1.20 (m, 8H, CH2 × 4); the following signals are discernible for (5R,1’Z,3’R)-6k: δ 5.56-5.48 (m, 1H, =CH), 5.34-5.24 (m, 1H, CH); 13C NMR (75 MHz, CDCl3) δ 176.5, 138.5, 134.1, 129.4, 88.2, 80.7, 79.7, 56.1, 34.7, 32.6, 28.6, 28.4, 28.2, 27.3, 24.5.

Synthetic application in the synthesis of naturally occurring γ-alkylic γ-lactones 1. Synthesis of (R)-4-tetradecalactone Synthesis of (Ra)-4,5-tetradecadienoic acid (Ra)-5j (zj-4-187,4-190)

Following Typical Procedure IV, the reaction of CuBr2 (0.6764 g, 3.0 mmol, 99%), (S)-3a (3.8705 g, 15 mmol, 98%), 1b (2.2730 g, 18 mmol)/dioxane (15 mL), and nonanaldehyde 2j (4.0 mL, d = 0.8277 g cm-3, 3.1784 g, 22.38 mmol, 96%)/dioxane (10 mL) for 16 h afforded (Ra)-4bj (1.6250 g) [(eluent: petroleum ether

65

(60-90 oC)/diethyl ether = 100/1 (500 mL × 2) to 50/1 (400 mL)] as a liquid, which was then submitted to next step. Following Typical Procedure V, the reaction of (Ra)-4bj (1.6250 g, 6.45 mmol, prepared above), EtOH/H2O = 1:1 by volume (pre-mixed by using 25 mL of H2O and 25 mL of EtOH), and LiOH·H2O (0.4290 g, 9.675 mmol, 95%) for 18 h afforded (Ra)-5j21 (1.3001 g, 39%, 2 steps) [(eluent: petroleum ether (60-90 oC)/ethyl acetate = 20/1 (440 mL) to 10/1 (550 mL × 3) to 5/1 (600 mL)] as a liquid: 95% ee (determined by the corrsponding esterification product (Ra)-4bj); [α]D20 = -65.3 (c = 1.025, CHCl3); 1

H NMR (300 MHz, CDCl3) δ 10.35 (bs, 1H, COOH), 5.21-5.11 (m, 2H, =CH × 2),

2.48 (t, J = 7.2 Hz, 2H, CH2), 2.36-2.24 (m, 2H, CH2); 2.02-1.91 (m, 2H, CH2), 1.44-1.20 (m, 12H, CH2 × 6), 0.88 (t, J = 6.8 Hz, 3H, CH3);

13

C NMR (75 MHz,

CDCl3) δ 203.6, 179.8, 92.9, 89.2, 33.1, 31.9, 29.4, 29.3, 29.15, 29.10, 28.8, 23.5, 22.6, 14.1; IR (neat) ν (cm−1) 3666-2167 (COOH), 3031, 2953, 2925, 2855, 2664, 1964, 1712, 1435, 1411, 1378, 1336, 1279, 1250, 1211, 1173; MS (70 ev, EI) m/z (%) 224 (M+, 8.53), 126 (100), 84 (100), 81 (100).

Esterification for determination of the ee value of (Ra)-5j: synthesis of (Ra)-ethyl 4,5-tetradeca dienoate (Ra)-4bj (zj-4-198)

Following Typical Procedure III, the reaction of (Ra)-5j (0.1345 g, 0.6 mmol), EtI (0.06 mL, d = 1.94 g cm-3, 0.1152 g, 0.74 mmol, 99%), K2CO3 (0.2512 g, 1.8 mmol), and DMF (6 mL) for 13 h afforded (Ra)-4bj (0.1358 g, 90%) [eluent: petroleum ether (60-90 oC)/ethyl acetate = 100/1 (600 mL)] as a liquid: 95% ee (HPLC conditions: Chiralcel OZ-H column, n-hexane/i-PrOH = 400:1, 0.5 mL/min, λ = 214 nm, tR (major) = 15.4 min, tR (minor) = 14.1 min); [α]D20 = -60.1 (c = 1.00, CHCl3); 1H NMR (300 MHz, CDCl3) δ 5.18-5.09 (m, 2H, =CH × 2), 4.13 (q, J = 7.0 Hz, 2H, OCH2), 2.46-2.37 (m, 2H, CH2), 2.34-2.23 (m, 2H, CH2), 2.02-1.90 (m, 2H, CH2), 1.44-1.21 (m, 15H, CH3 + CH2 × 6), 0.88 (t, J = 6.8 Hz, 3H, CH3); 13C NMR

66

(75 MHz, CDCl3) δ 203.6, 173.1, 92.5, 89.5, 60.2, 33.4, 31.8, 29.4, 29.3, 29.1, 28.8, 23.9, 22.6, 14.2, 14.1; IR (neat) ν (cm−1) 2956, 2926, 2854, 1963, 1739, 1465, 1447, 1420, 1372, 1350, 1300, 1250, 1159, 1097, 1055, 1037; MS (70 ev, EI) m/z (%) 252 (M+, 4.90), 80 (100); HRMS calcd for C16H28O2 [M+]: 252.2089, found: 252.2085.

Synthesis of (S,E)-5-(1-decenyl)dihydro-2(3H)-furanone (S,E)-6j (zj-5-017)

Following Typical Procedure VI, the reaction of AgOTs (0.0142 g, 0.05 mmol, 98%), Au(LB-Phos)Cl (0.0299 g, 0.05 mmol), CHCl3 (5 mL), and (Ra)-5j (0.2240 g, 1.0 mmol)/CHCl3 (5 mL) for 3.0 h afforded (S,E)-6j11 (0.2158 g, 96%, (S,E)/(R,Z) = 97/3 determined by 1H NMR) [eluent: petroleum ether (60-90 oC)/ethyl acetate = 10/1 (220 mL) to 8/1 (450 mL)] ((S,E)/(R,Z) = 97/3 determined by 1H NMR of crude product) as an oil with pleasant flavor: 96% ee (HPLC conditions: Chiralcel OJ-H column, n-hexane/i-PrOH = 100:1, 1.0 mL/min, λ = 214 nm, tR(major) = 15.4 min, tR(minor) = 13.5 min; [α]D20 = +27.3 (c = 0.99, CHCl3); (Lit.11 [α]D26 = +30.2 (c = 2.12, CHCl3)); 1H NMR (300 MHz, CDCl3) δ 5.81 (dtd, J1 = 15.3 Hz, J2 = 6.6 Hz, J3 = 0.9

Hz, 1H, =CH), 5.49 (ddt, J1 = 15.3 Hz, J2 = 7.2 Hz, J3 = 1.1 Hz, 1H, =CH), 4.89 (q, J = 7.2 Hz, 1H, CH), 2.58-2.48 (m, 2H, CH2), 2.46-2.31 (m, 1H, one proton from CH2), 2.11-1.89 (m, 3H, CH2 + one proton from CH2), 1.47-1.18 (m, 12H, CH2 × 6), 0.88 (t, J = 6.6 Hz, 3H, CH3); the following signals are discernible for (R,Z)-6j: δ 5.71-5.61 (m, 1H, =CH), 5.31-5.21 (m, 1H, CH);

13

C NMR (75 MHz, CDCl3) δ 176.8, 135.2,

127.2, 80.8, 31.8, 31.5, 29.1, 28.9, 28.8, 28.5, 28.45, 28.38, 22.3, 13.8; IR (neat) ν (cm−1) 2956, 2925, 2854, 1778, 1673, 1460, 1423, 1378, 1327, 1299, 1216, 1176, 1123, 1011; GC-MS (GC condition: injector: 280 oC; column: DB5 column 30 m × 0.25 mm, temperature programming: 60 oC (2 min), 20 oC/min to 280 oC, 280 oC (30 min); detector: 280 oC) (70 ev, EI) m/z (%) for (S,E)-6j: tR (major) = 4.03 min: 224 (M+, 0.94), 111 (100); for (R,Z)-6j tR (minor) = 3.98 min: 224 (M+, 1.27), 111 (100).

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Synthesis of (R)-5-decyldihydro-2(3H)-furanone (R)-4-tetradecalactone4 (zj-5-093)

Typical Procedure XV: To a reaction tube were added (S,E)-6j (0.1122 g, 0.5 mmol), EtOAc (3 mL), and Pd/C (10% on C, dry, 0.0266 g, 0.025 mmol) sequentially. Then the reaction tube was placed in an autoclave. The resulting mixture was stirred under H2 (25 atm) at room temperature for 36 h and then filtered through a short column of silica gel with Et2O (15 mL × 3). After evaporation, the residue was purified by chromatography [eluent: petroleum ether (60-90 oC)/ethyl acetate = 10/1 (550 mL)] on silica gel to afford (R)-4-tetradecalactone22 (0.1109 g, 98%) as an oil with pleasant flavor: 93% ee (GC conditions: CP-Chirasil-DEX CB column (25 m × 0.25 mm × 0.25 μm); carrier = He; injector = 145 oC; detector (FID, H2) = 200 oC; oven temperature = 140 oC to 200 oC (5 oC/min); tR(major) = 61.3 min, tR(minor) = 62.9 min; [α]D20 = +28.5 (c = 0.99, CHCl3); (Lit.11 [α]D26 = +29.95 (c = 2.739, CHCl3)); 1

H NMR (300 MHz, CDCl3) δ 4.54-4.44 (m, 1H, CH), 2.59-2.48 (m, 2H, CH2),

2.39-2.26 (m, 1H, one proton from CH2), 1.93-1.78 (m, 1H, one proton from CH2), 1.78-1.67 (m, 1H, one proton from CH2), 1.67-1.53 (m, 1H, one proton from CH2), 1.51-1.18 (m, 16 H, CH2 × 8), 0.88 (t, J = 6.8 Hz, 3H, CH3);

13

C NMR (75 MHz,

CDCl3) δ 177.2, 80.9, 35.4, 31.7, 29.43, 29.39, 29.3, 29.20, 29.17, 28.7, 27.9, 25.1, 22.5, 14.0; IR (neat) ν (cm−1) 2925, 2854, 1779, 1463, 1420, 1376, 1352, 1285, 1216, 1178, 1127, 1019; MS (70 ev, EI) m/z (%) 227 (M+ + 1, 34.74), 226 (M+, 0.63), 85 (100).

2. Synthesis of (S)-4-tetradecalactone Synthesis of (Sa)-4,5-tetradecadienoic acid (Sa)-5j (zj-4-186,4-189)

Following Typical Procedure IV, the reaction of CuBr2 (0.6764 g, 3.0 mmol,

68

99%), (R)-3a (3.8711 g, 15 mmol), 1b (2.2745 g, 18 mmol)/dioxane (15 mL), and nonanaldehyde 2j (4.0 mL, d = 0.8277 g cm-3, 3.1784 g, 22.38 mmol)/dioxane (10 mL) for 16 h afforded (Sa)-4bj (1.6104 g) [(eluent: petroleum ether (60-90 oC)/diethyl ether = 100/1 (500 mL × 2) to 50/1 (400 mL)] as a liquid, which was then submitted to next step without further characterization. Following Typical Procedure V, the reaction of (Sa)-4bj (1.6104 g, 6.4 mmol, prepared above), EtOH/H2O = 1:1 by volume (pre-mixed by using 25 mL of H2O and 25 mL of EtOH), and LiOH·H2O (0.4240 g, 9.6 mmol, 95%) for 18 h afforded (Sa)-5j21 (1.2931 g, 39%, 2 steps) [(eluent: petroleum ether (60-90 oC)/ethyl acetate = 20/1 (420 mL) to 10/1 (550 mL × 3) to 5/1 (600 mL)] as an oil: 97% ee (determined by the corrsponding esterification product (Sa)-4bj); [α]D20 = +66.5 (c = 1.005, CHCl3); 1H NMR (300 MHz, CDCl3) δ 10.15 (bs, 1H, COOH), 5.22-5.10 (m, 2H, =CH × 2), 2.48 (t, J = 7.4 Hz, 2H, CH2), 2.38-2.23 (m, 2H, CH2), 2.03-1.90 (m, 2H, CH2), 1.45-1.18 (m, 12H, CH2 × 6), 0.88 (t, J = 6.8 Hz, 3H, CH3); 13C NMR (75 MHz, CDCl3) δ 203.6, 179.7, 92.9, 89.2, 33.1, 31.9, 29.4, 29.3, 29.14, 29.10, 28.8, 23.5, 22.6, 14.1; IR (neat) ν (cm−1) 3728-2188 (COOH), 3033, 2956, 2925, 2854, 2667, 1964, 1713, 1436, 1412, 1378, 1336, 1278, 1249, 1211, 1180, 1042, 1075; MS (70 ev, EI) m/z (%) 224 (M+, 6.98), 126 (100), 81 (100).

Esterification for determination of the ee value of (Sa)-5j: synthesis of (Sa)-ethyl 4,5-tetradeca dienoate (Sa)-4bj (zj-4-199)

Following Typical Procedure III, the reaction of (Sa)-5j (0.1340 g, 0.6 mmol), EtI (0.06 mL, d = 1.94 g cm-3, 0.1152 g, 0.74 mmol, 99%), K2CO3 (0.2507 g, 1.8 mmol), and DMF (6 mL) for 13 h afforded (Sa)-4bj (0.1385 g, 92%) [eluent: petroleum ether (60-90 oC)/ethyl acetate = 100/1 (600 mL)] as a liquid: 97% ee (HPLC conditions: Chiralcel OZ-H column, n-hexane/i-Pr = 400:1, 0.5 mL/min, λ = 214 nm, tR (major) = 8.9 min, tR (minor) = 9.4 min); [α]D20 = + 61.6 (c = 0.995, CHCl3) 1H NMR (300 MHz,

69

CDCl3) δ 5.18-5.09 (m, 2H, =CH × 2), 4.13 (q, J = 7.2 Hz, 2H, OCH2), 2.46-2.37 (m, 2H, CH2), 2.35-2.24 (m, 2H, CH2), 2.02-1.91 (m, 2H, CH2), 1.45-1.18 (m, 15H, CH3 + CH2 × 6), 0.88 (t, J = 6.8 Hz, 3H, CH3); 13C NMR (75 MHz, CDCl3) δ 203.6, 172.9, 92.3, 89.4, 60.1, 33.3, 31.8, 29.3, 29.2, 29.0, 28.8, 23.8, 22.5, 14.1, 13.9; IR (neat) ν (cm−1) 2957, 2926, 2855, 1963, 1739, 1464, 1418, 1372, 1349, 1300, 1249, 1159, 1097, 1038; MS (70 ev, EI) m/z (%) 252 (M+, 6.68), 80 (100); HRMS calcd for C16H28O2 [M+]: 252.2089, found: 252.2087.

Synthesis of (S)-5-decyldihydro-2(3H)-furanone (S)-4-tetradecalactone (zj-5-090)

Following Typical Procedure XV, the reaction of (R,E)-6j (0.1121 g, 0.5 mmol, prepared above, see page 35)/EtOAc (3 mL) and Pd/C (10% on C, dry, 0.0266 g, 0.025 mmol) for 36 h afforded (S)-4-tetradecalactone11 (0.1113 g, 98%) [eluent: petroleum ether (60-90 oC)/ethyl acetate = 10/1 (550 mL)] as an oil with pleasant flavor: 93% ee (GC conditions: CP-Chirasil-DEX CB column (25 m × 0.25 mm × 0.25 μm); carrier: He; injector: 145 oC; detector (FID, H2): 200 oC; oven temperature: 140 o

C to 200 oC (5 oC/min); tR(major) = 62.7 min, tR(minor) = 61.4 min; [α]D20 = -28.6 (c

= 1.01, CHCl3); (Lit.11 [α]D26 = -36.76 (c = 2.4, CHCl3)); 1H NMR (300 MHz, CDCl3) δ 4.55-4.44 (m, 1H, =CH), 2.61-2.50 (m, 2H, CH2), 2.40-2.26 (m, 1H, one proton from CH2), 1.95-1.79 (m, 1H, one proton from CH2), 1.79-1.67 (m, 1H, one proton from CH2), 1.66-1.53 (m, 1H, one proton from CH2), 1.51-1.17 (m, 16 H, CH2 ×8), 0.88 (t, J = 6.8 Hz, 3H, CH3);

13

C NMR (75 MHz, CDCl3) δ 177.2, 80.9, 35.5, 31.7, 29.43,

29.39, 29.3, 29.20, 29.17, 28.7, 27.9, 25.1, 22.5, 14.0; IR (neat) ν (cm−1) 2956, 2922, 2853, 1754, 1471, 1425, 1384, 1186, 1023, 1008; MS (70 ev, EI) m/z (%) 227 (M+ + 1, 49.33), 226 (M+, 0.88), 85 (100).

3. Synthesis of (R)-γ-palmitolactone Synthesis of (Ra)-4,5- hexadecadienoic acid (Ra)-5l (zj-3-166,3-171)

70

Following Typical Procedure IV, the reaction of CuBr2 (0.6766 g, 3.0 mmol, 99%), (S)-3a (3.8771 g, 15 mmol, 98%), 1b (2.2785 g, 18 mmol)/dioxane (20 mL), and undecanylaldehyde 2l (3.8 mL, d = 0.825 g cm-3, 3.135 g, 17.9 mmol)/dioxane (5 mL) for 16 h afforded (Ra)-4bl (1.6328 g) [(eluent: petroleum ether (60-90 oC)/diethyl ether = 100/1 (500 mL × 2) to 50/1 (500 mL × 2) to 20/1 (210 mL)] as a liquid, which was then submitted to next step. Following Typical Procedure V, the reaction of (Ra)-4bl (1.6328 g, 5.83 mmol, prepared above), EtOH/H2O = 1:1 by volume (pre-mixed by using 29 mL of H2O and 29 mL of EtOH), and LiOH·H2O (0.3869 g, 8.745 mmol, 95%) for 18 h afforded (Ra)-5l (1.2436 g, 33%, 2 steps) [(eluent: petroleum ether (60-90 oC)/ethyl acetate = 20/1 (500 mL) to 10/1 (500 mL × 3) to 5/1 (360 mL)] as a liquid: 97% ee (determined by the corrsponding esterification product (Ra)-4al); [α]D20 = -59.8 (c = 0.99, CHCl3); 1

H NMR (300 MHz, CDCl3) δ 10.25 (bs, 1H, COOH), 5.20-5.11 (m, 2H, =CH × 2),

2.48 (t, J = 6.9 Hz, 2H, CH2), 2.36-2.24 (m, 2H, CH2); 2.02-1.91 (m, 2H, CH2), 1.44-1.17 (m, 16H, CH2 × 8), 0.88 (t, J = 6.8 Hz, 3H, CH3);

13

C NMR (75 MHz,

CDCl3) δ 203.6, 179.7, 92.9, 89.2, 33.1, 31.9, 29.64, 29.61, 29.5, 29.3, 29.15, 29.11, 28.8, 23.5, 22.7, 14.1; IR (neat) ν (cm−1) 3558-2221 (COOH), 3037, 2956, 2925, 2854, 2664, 1963, 1712, 1436, 1412, 1377, 1334, 1279, 1249, 1211, 1173, 1046, 1017; MS (70 ev, EI) m/z (%) 252 (M+, 5.43), 126 (100); HRMS calcd. for C16H28O2 [M + H+]: 252.2089, found: 252.2088.

Esterification for determination of the ee value of (Ra)-5l: synthesis of (Ra)-ethyl 4,5-hexadeca dienoate (Ra)-4al 5(zj-3-184)

71

To a Schlenk tube were added (Ra)-5l (0.0505 g, 0.2 mmol, prapared above) and DMF (2 mL). Then K2CO3 (0.0830 g, 0.6 mmol) and BnBr (0.03 mL, d = 1.43 g cm-3, 0.042 g, 0.246 mmol, 98%) were added sequentially. After continuous stirring at room temperature for 18 h, the reaction was complete as monitored by TLC. After quenching with water (10 mL) and being stirred for 10 min, the aqueous solution was extracted with Et2O (10 mL × 3). The combined organic layer was washed with H2O and brine, and dried over anhydrous Na2SO4. Filtration, evaporation, and column chromatography on silica gel gave (Ra)-4al (0.0635 g, 93%) [eluent: petroleum ether (60-90 oC)/ethyl acetate = 100/1 (500 mL)] as a liquid: 97% ee (HPLC conditions: Chiralcel IA column, n-hexane, 0.8 mL/min, λ = 214 nm, tR (major) = 20.0 min, tR (minor) = 22.4 min); [α]D20 = -49.8 (c = 1.00, CHCl3); 1H NMR (300 MHz, CDCl3) δ 7.33-7.20 (m, 5H, ArH), 5.11-4.97 (m, 4H, =CH × 2 + CH2), 2.44-2.35 (m, 2H, CH2), 2.29-2.19 (m, 2H, CH2), 1.92-1.80 (m, 2H, CH2), 1.34-1.11 (m, 16H, CH2 × 8), 0.80 (t, J = 6.6 Hz, 3H, CH3); 13C NMR (75 MHz, CDCl3) δ 203.6, 172.9, 136.0, 128.5, 128.1, 92.6, 89.4, 66.1, 33.4, 31.9, 29.6, 29.4, 29.3, 29.1, 28.8, 23.8, 22.7, 14.1; IR (neat) ν (cm−1) 3090, 3066, 3033, 2956, 2925, 2853, 1962, 1740, 1498, 1455, 1379, 1353, 1153; MS (70 ev, EI) m/z (%) 343 (M+ + 1, 7.75), 342 (M+, 4.17), 91 (100); HRMS calcd for C23H34O2 [M+]: 342.2559, found: 342.2552.

Synthesis of (S,E)-5-(1-dodecenyl)dihydro-2(3H)-furanone (S,E)-6l (zj-3-181)

Following Typical Procedure VI, the reaction of AgOTs (0.0142 g, 0.05 mmol, 98%), Au(LB-Phos)Cl (0.0299 g, 0.05 mmol), CHCl3 (5 mL), and (Ra)-5l (0.2524 g, 1.0 mmol)/CHCl3 (5 mL) for 2.5 h afforded (S,E)-6l (0.2492 g, 99%, (S,E)/(R,Z) = 98/2 determined by 1H NMR) [eluent: petroleum ether (60-90 oC)/ethyl acetate = 10/1 (250 mL) to 8/1 (400 mL)] ((S,E)/(R,Z) = 97/3 determined by 1H NMR of crude product) as an oil with pleasant flavor: 97% ee (HPLC conditions: Chiralcel AS-H column, hexane/i-PrOH = 95:5, 1.0 mL/min, λ = 214 nm, tR(major) = 11.8 min,

72

tR(minor) = 10.6 min; [α]D20 = +24.2 (c = 1.005, CHCl3); 1H NMR (300 MHz, CDCl3) δ 5.80 (dt, J1 = 15.3 Hz, J2 = 7.1 Hz, 1H, =CH), 5.49 (ddt, J1 = 15.0 Hz, J2 = 7.1 Hz, J3 = 1.3 Hz, 1H, =CH), 4.89 (q, J = 6.8 Hz, 1H, CH), 2.57-2.48 (m, 2H, CH2), 2.43-2.31 (m, 1H, one proton from CH2), 2.12-1.90 (m, 3H, CH2 + one proton from CH2), 1.46-1.17 (m, 16H, CH2 × 8), 0.88 (t, J = 6.8 Hz, 3H, CH3); the following signals are discernible for (R,Z)-6l: δ 5.71-5.61 (m, 1H, =CH), 5.30-5.21 (m, 1H, CH); 13

C NMR (75 MHz, CDCl3) δ 176.8, 135.3, 127.2, 80.9, 31.8, 31.6, 29.33, 29.30, 29.2,

29.1, 28.8, 28.6, 28.5, 28.4, 22.4, 13.8; IR (neat) ν (cm−1) 2925, 2854, 1778, 1672, 1462, 1421, 1376, 1325, 1300, 1216, 1176, 1123, 1009; GC-MS (GC condition: injector: 280 oC; column: DB5 column 30 m × 0.25 mm, temperature programming: 60 oC (2 min), 20 oC/min to 280 oC, 280 oC (30 min); detector: 280 oC) (70 ev, EI) m/z (%) for (S,E)-6l: tR (major) = 7.8 min: 252 (M+, 1.16), 111 (100); for (R,Z)-6l tR (minor) = 7.6 min: 252 (M+, 3.23), 111 (100); HRMS calcd. for C16H28O2 [M +]: 252.2089, found: 252.2086.

Synthesis of (R)-5-dodecyldihydro-2(3H)-furanone (R)-γ-palmitolactone (zj-5-044)

Following Typical Procedure XV, the reaction of (S,E)-6l (0.1261 g, 0.5 mmol)/EtOAc (4 mL), Pd/C (0.0128 g, 10% on C, dry, 0.012 mmol), and EtOAc (3 mL) for 60 h afforded (R)-γ-palmitolactone23 (0.1175 g, 92%) [eluent: petroleum ether (60-90 oC)/ethyl acetate = 10/1 (850 mL)] as an oil with pleasant flavor: 96% ee (GC conditions: CP-Chirasil-DEX CB column (25 m × 0.25 mm × 0.25 μm); carrier: He; injector: 145 oC; detector (FID, H2): 200 oC; oven temperature: 130 oC to 200 oC (5 o

C/min); tR (major) = 121.3 min, tR (minor) = 124.2 min; [α]D20 = +26.9 (c = 0.99,

CHCl3); 1H NMR (300 MHz, CDCl3) δ 4.54-4.43 (m, 1H, CH), 2.57-2.48 (m, 2H, CH2), 2.38-2.26 (m, 1H, one proton from CH2), 1.92-1.81 (m, 1H, one proton from CH2), 1.79-1.67 (m, 1H, one proton from CH2), 1.65-1.53 (m, 1H, one proton from

73

CH2), 1.50-1.18 (m, 20H, CH2 × 10), 0.88 (t, J = 6.8 Hz, 3H, CH3);

13

C NMR (75

MHz, CDCl3) δ 177.1, 80.9, 35.5, 31.8, 29.52, 29.50, 29.4, 29.3, 29.2, 28.7, 27.9, 25.1, 22.5, 14.0; IR (neat) ν (cm−1) 2925, 2854, 1780, 1462, 1421, 1376, 1352, 1285, 1216, 1177, 1127, 1021; MS (70 ev, EI) m/z (%) 255 (M+ + 1, 60.83), 254 (M+, 1.65), 85 (100).

4. Gram Scale Synthesis of (R)-4-Decalactone Synthesis of (Ra)-4,5-decadienoic acid (Ra)-5b (zj-6-108,6-111)

Following Typical Procedure I, the reaction of CuBr2 (1.3514 g, 6.0 mmol, 99%), (S)-2-(pyrrolidin-2-yl)propan-2-ol (S)-3b (3.8415 g, 30 mmol), 1b (5.6719 g, 45 mmol)/dioxane (60 mL), and 2b (4.8 mL, d = 0.81 g cm-3, 3.888 g, 45.21 mmol)/dioxane (30 mL) afforded (Ra)-4bb (3.0621 g) [(eluent: petroleum ether (60-90 C)/diethyl ether = 100/1 (500 mL × 2) to 50/1 (500 mL) to 30/1 (500 mL)] as a

o

liquid, which was then submitted to next step. Following Typical Procedure V, the reaction of (Ra)-4bb (3.0621 g, 15.6 mmol, prepared above), EtOH/H2O = 1:1 by volume (pre-mixed by using 35 mL of H2O and 35 mL of EtOH), and LiOH·H2O (1.0352 g, 23.4 mmol, 95%) afforded (Ra)-5b (2.2406 g, 45%, 2 steps) [(eluent: petroleum ether (60-90 oC)/ethyl acetate = 20/1 (420 mL) to 15/1 (480 mL) to 10/1 (660 mL)] as a liquid: 98% ee (determined by the corrsponding esterification product (Ra)-4bb); [α]D20 = -77.7 (c = 0.99, CHCl3); 1H NMR (300 MHz, CDCl3) δ 11.55 (bs, 1H, COOH), 5.21-5.11 (m, 2H, =CH × 2), 2.48 (t, J = 7.4 Hz, 2H, CH2), 2.36-2.22 (m, 2H, CH2), 2.05-1.90 (m, 2H, CH2), 1.46-1.25 (m, 4H, CH2 × 2), 0.90 (t, J = 7.2 Hz, 3H, CH3); 13C NMR (75 MHz, CDCl3) δ 203.6, 180.0, 92.8, 89.2, 33.1, 31.2, 28.5, 23.4, 22.1, 13.8.

74

Esterification for determination of the ee value of (Ra)-5b: synthesis of (Ra)-ethyl 4,5-decadienoate (Ra)-4bb (zj-6-116)

Following Typical Procedure III, the reaction of (Ra)-5b (0.0831 g, 0.5 mmol)/DMF (5 mL), K2CO3 (0.2072 g, 1.5 mmol), and EtI (0.05 mL, d = 1.94 g cm-3, 0.0951 g, 0.61 mmol, 98%) for 18 h afforded (Ra)-4bb (0.0905 g, 93%) [eluent: petroleum ether (60-90 oC)/ethyl acetate = 100/1 (500 mL) to 50/1 (300 mL)] as a liquid: 98% ee (HPLC conditions: Chiralcel OZ-H column, n-hexane, 1.0 mL/min, λ = 214 nm, tR (major) = 27.1 min, tR (minor) = 24.5 min); [α]D20 = -69.6 (c = 1.04, CHCl3); 1H NMR (300 MHz, CDCl3) δ 5.20-5.08 (m, 2H, =CH × 2), 4.13 (q, J = 7.2 Hz, 2H, OCH2), 2.47-2.37 (m, 2H, CH2), 2.35-2.24 (m, 2H, CH2), 2.04-1.92 (m, 2H, CH2), 1.43-1.30 (m, 4H, CH2 × 2), 1.26 (t, J = 7.1 Hz, 3H, CH3) 0.90 (t, J = 6.9 Hz, 3H, CH3);

13

C NMR (75 MHz, CDCl3) δ 203.7, 173.0, 92.4, 89.4, 60.1, 33.4, 31.2,

28.5, 23.8, 22.1, 14.1, 13.8.

Gram Scale Synthesis of (R)-5-hexyldihydro-2(3H)-furanone (R)-4-Decalactone (zj-6-170)

Following Typical Procedure XV, the reaction of (S,E)-6b (1.1772 g, 7.0 mmol, prepared above, see page 36)/EtOAc (20 mL), and Pd/C (10% on C, dry, 0.3724 g, 0.35 mmol) for 36 h afforded (R)-4-decalactone24 (1.1635 g, 98%) [eluent: petroleum ether (60-90 oC)/diethyl ether = 5/1 (500 mL × 2) to 3/1 (400 mL)] as an oil with pleasant flavor: 94% ee (GC conditions: CP-Chirasil-DEX CB column (25 m × 0.25 mm × 0.25 μm); carrier: N2 at 10 psi; injector: 250 oC; detector (FID, H2): 250 oC; oven temperature: 60 oC to 180 oC (5 oC/min); tR(major) = 49.6 min, tR(minor) = 50.1

75

min); [α]D20 = +40.0 (c = 0.975, CHCl3); (Lit.24 [α]D26 = +31 (c = 1.2, CHCl3)); 1H NMR (300 MHz, CDCl3) δ 4.55-4.43 (m, 1H, =CH), 2.60-2.45 (m, 2H, CH2), 2.40-2.25 (m, 1H, one proton from CH2), 1.94-1.80 (m, 1H, one proton from CH2), 1.80-1.67 (m, 1H, one proton from CH2), 1.66-1.53 (m, 1H, one proton from CH2), 1.52-1.19 (m, 8 H, CH2 × 4), 0.89 (t, J = 6.9 Hz, 3H, CH3);

13

C NMR (75 MHz,

CDCl3) δ 177.2, 81.0, 35.5, 31.5, 28.7, 27.9, 25.1, 22.4, 13.9; IR (neat) ν (cm−1) 2956, 2932, 2858, 1778, 1461, 1422, 1379, 1351, 1292, 1218, 1181, 1127, 1022; MS (70 ev, EI) m/z (%) 171 (M+ + 1, 30.46), 170 (M+, 0.13), 85 (100).

76

10

7.350 7.342 7.333 7.308 7.289 7.261 7.221

8

2017-09-03 21:39:37.968 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz

5.00

6

5.176 5.166 5.145 5.136 5.125 5.109 5.102 5.091 5.080 5.070 5.060 5.048 4.00

Supplementary Figure 1. 1H NMR (300 MHz, CDCl3) spectrum for (Ra)-4aa.

77

4

2.00

2.01

2

2.00

10.31

3.00

0

PPM

2.491 2.487 2.465 2.440 2.362 2.346 2.333 2.325 2.316 2.306 2.300 2.289 2.280 2.268 1.973 1.951 1.926 1.916 1.894 1.382 1.358 1.317 1.294 1.258 0.895 0.873 0.850 -0.000

zj-8-078

Supplementary Figures

Supplementary Figure 2. 13C NMR (75 MHz, CDCl3) spectrum for (Ra)-4aa.

78

200

172.751

2017-09-03 21:44:49.296 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 74 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz

150

zj-8-078

100

50

33.256 31.739 29.028 28.991 28.743 23.724 22.538 13.981

66.016

77.423 77.000 76.568

92.516 89.335

128.391 128.061 128.033

135.947

203.562

0

PPM

电 (mv) 压

zj-8-078 实验时间:2017-09-03,21:25:58 谱图文件:D:\浙大智达\N2000\样品\S20170903212558.org 方法文件:D:\浙大智达\N2000\djx.mtd

实验者:zj 报告时间:2017-09-04,10:31:35 积分方法:面积归一法

实验内容简介: OJ-H,214,n-hexane/i-PrOH = 200/1, 0.8

色谱图(S20170903212558.org)

1,400 1,300 1,200 1,100 1,000

电压(mv)

900 800 700 600 500 400 300 200 100 0 0

1

2

3

4

5

6

7

8

9

10

11

12

13

14

时间(min)

峰号 1 2

峰名

保留时间

分析结果表 峰高

8.462 9.617

总计

Supplementary Figure 3. HPLC spectrum for (Ra)-4aa. 79

峰面积

含量

70784.430 1354498.625

573324.122 21785467.000

2.5642 97.4358

1425283.055

19287909.438

100.0000

电 (mv) 压

zj-8-079 实验时间:2017-09-03,21:05:00 谱图文件:D:\浙大智达\N2000\样品\S20170903210500.org 方法文件:D:\浙大智达\N2000\djx.mtd

实验者:zj 报告时间:2017-09-04,10:21:11 积分方法:面积归一法

实验内容简介: OJ-H,214,n-hexane/i-PrOH = 200/1, 0.8

色谱图(S20170903210500.org) 1,200 1,100 1,000 900

电压(mv)

800 700 600 500 400 300 200 100 0 2

4

6

8

10

12

14

16

时间(min)

峰号 1 2

峰名

保留时间

分析结果表 峰高

8.408 9.640

总计

Supplementary Figure 4. HPLC spectrum for rac-4aa. 80

峰面积

含量

906405.375 1178140.750

15571489.000 15385857.000

50.2998 49.7002

2084546.125

30957346.000

100.0000

Supplementary Figure 5. 1H NMR (300 MHz, CDCl3) spectrum for (Ra)-5a.

81

12

11.207

10

0.73

2017-05-15 10:13:03.203 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz

8

5.188 5.172 5.157 5.140 5.125

6

zj-8-040

2.00

4

2.01

2.00

2

2.00

10.35

3.01

0

2.508 2.482 2.458 2.338 2.323 2.299 2.284 2.280 2.007 1.985 1.966 1.952 1.927 1.379 1.355 1.271 0.904 0.882 0.859 -0.000

7.265

PPM

Supplementary Figure 6. 13C NMR (75 MHz, CDCl3) spectrum for (Ra)-5a.

82

179.737

200

2017-05-15 15:28:09.281 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 5336 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz

150

zj-8-040

100

50

14.064

33.127 31.841 29.111 28.826 23.494 22.630

77.423 77.000 76.577

92.883 89.216

203.672

0

PPM

Supplementary Figure 7. 1H NMR (300 MHz, CDCl3) spectrum for (Ra)-4ba.

83

10

7.273

8

2017-05-10 09:27:13.648 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz

5.167 5.152 5.136 5.121 5.103

6

4.167 4.144 4.120 4.096 2.00

4

2.00

zj-8-043

2.00

2.01

2

2.02

13.32

3.02

0

2.441 2.414 2.389 2.332 2.316 2.307 2.300 2.289 2.276 2.267 2.255 1.980 1.964 1.956 1.948 1.939 1.923 1.403 1.379 1.355 1.283 1.273 1.259 1.235 0.903 0.882 0.859 -0.000

PPM

Supplementary Figure 8. 13C NMR (75 MHz, CDCl3) spectrum for (Ra)-4ba.

84

203.553

200

2017-05-10 14:27:34.234 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 148 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz

150

zj-8-043

100

50

33.284 31.749 29.028 28.991 28.761 23.761 22.538 14.082 13.944

60.096

77.432 77.000 76.577

92.369 89.381

172.953

0 PPM

m)v(压

zj-8-043-od-h-100-0-0.5-214 实验时间:2017-5-25,16:18:55 谱图文件:D:\zhuguangjiong\zj\20170525\zj-8-043-od-h-100-00.5-214..org

报告时间:2017-5-25,17:01:38

实验内容简介:

色谱图(zj-8-043-od-h-100-0-0.5-214..org)

1,500 1,400 1,300 1,200 1,100 1,000

800 700

15.795

电压(mv)

900

600 500 400 300

15.352

200 100 0 0

1

2

3

4

5

6

7

8

9

10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25

时间(min)

峰号 1 2

峰名

保留时间

分析结果表 峰高

15.352 15.795

总计

Supplementary Figure 9. HPLC spectrum for (Ra)-4ba. 85

峰面积

含量

18955.471 520920.969

279392.031 15151092.000

1.8106 98.1894

539876.439

15430484.031

100.0000

m)v(压

zj-8-020-od-h-100-0-0.5-214 实验时间:2017-5-25,15:06:21 谱图文件:D:\zhuguangjiong\zj\20170525\zj-8-020-od-h-100-00.5-214.org

报告时间:2017-5-25,16:33:57

实验内容简介:

色谱图(zj-8-020-od-h-100-0-0.5-214.org)

1,500 1,400 1,300 1,200 1,100 1,000

800 14.978

700 600 500

15.883

电压(mv)

900

400 300 200 100 0 0

1

2

3

4

5

6

7

8

9

10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25

时间(min)

峰号 1 2

峰名

保留时间

分析结果表 峰高

14.978 15.883

总计

Supplementary Figure 10. HPLC spectrum for rac-4ba.

86

峰面积

含量

487824.688 409940.844

11432328.000 11590101.000

49.6573 50.3427

897765.531

23022429.000

100.0000

Supplementary Figure 11. 1H NMR (300 MHz, CDCl3) spectrum for (Ra)-5b.

87

11.418

12

0.97

10

2016-05-07 23:22:11.546 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz

8

5.194 5.184 5.174 5.169 5.153 5.137 5.122 5.114

6

zj-6-053

1.97

4

1.98

2.00

2

2.00

4.10 3.03

0

PPM

2.502 2.477 2.453 2.335 2.321 2.305 2.296 2.282 2.253 2.014 1.995 1.974 1.958 1.934 1.428 1.418 1.398 1.391 1.372 1.360 1.348 1.336 1.323 1.296 1.257 0.919 0.895 0.871 0.000

7.267

Supplementary Figure 12. 13C NMR (75 MHz, CDCl3) spectrum for (Ra)-5b.

88

200

179.893

2016-05-07 23:34:43.625 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 196 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz

150

100

50

zj-6-053

13.797

33.146 31.206 28.476 23.485 22.134

77.423 77.000 76.568

92.782 89.207

203.691

0

PPM

Supplementary Figure 13. 1H NMR (300 MHz, CDCl3) spectrum for (Ra)-4bb.

89

7.304

10

8

2016-05-09 21:09:21.765 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz

6

1.96

4

2.00

zj-6-055

2.00

2.00

2

2.00

3.03

4.01 3.00

0

2.437 2.431 2.410 2.384 2.330 2.314 2.305 2.298 2.287 2.277 2.265 2.246 2.012 1.997 1.988 1.975 1.964 1.956 1.951 1.932 1.420 1.411 1.393 1.376 1.364 1.352 1.340 1.328 1.281 1.257 1.233 0.922 0.899 0.875 -0.000

4.165 4.142 4.118 4.094

5.164 5.148 5.132 5.117 5.102

PPM

Supplementary Figure 14. 13C NMR (75 MHz, CDCl3) spectrum for (Ra)-4bb.

90

172.953

203.654

200

2016-05-09 21:20:30.375 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 171 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz

150

zj-6-055

100

50

14.100 13.733

33.394 31.188 28.458 23.844 22.061

60.115

77.423 77.000 76.577

92.314 89.427

0

PPM

zj-6-055-pc-2-100-0-0.7-214 实验时间:2016-06-23,13:21:42 谱图文件:D:\zhuguangjiong\zj\20160617\zj-6-055-pc-2-100-00.7-214.org

报告时间:2016-06-23,14:23:27

实验内容简介:

色谱图(zj-6-055-pc-2-100-0-0.7-214.org)

300 280 260 240 220 200

电压(mv)

180 160 140 120

44.773

100 80 60

38.427

40 20 0 -20 0

2

4

6

8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50 52 54

时间(min)

峰号 1 2

峰名

保留时间

分析结果表 峰高

38.427 44.773

总计

Supplementary Figure 15. HPLC spectrum for (Ra)-4bb. 91

峰面积

含量

2442.978 54326.734

90536.805 5309446.500

1.6766 98.3234

56769.713

5399983.305

100.0000

zj-6-054-pc-2-100-0-0.7-214 实验时间:2016-06-23,12:22:21 谱图文件:D:\zhuguangjiong\zj\20160617\zj-6-054-pc-2-100-00.7-214.org

报告时间:2016-06-23,14:18:40

实验内容简介:

色谱图(zj-6-054-pc-2-100-0-0.7-214.org)

800 750 700 650 600 550

电压(mv)

500 450 400 350 300 200 150 100

42.598

35.650

250

50 0 0

2

4

6

8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50 52 54

时间(min)

峰号 1 2

峰名

保留时间

分析结果表 峰高

35.650 42.598

总计

Supplementary Figure 16. HPLC spectrum for rac-4bb. 92

峰面积

含量

127000.523 103346.539

13396767.000 13652672.000

49.5270 50.4730

230347.063

27049439.000

100.0000

Supplementary Figure 17. 1H NMR (300 MHz, CDCl3) spectrum for (Ra)-5c.

93

12

0.95

10

2015-07-04 18:55:11.515 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz

8

6

5.182 5.166 5.152 5.135 5.120 2.00

zj-4-033

4

2.00

2.00

2

2.00

18.52

3.00

0

2.499 2.476 2.451 2.333 2.310 2.302 2.294 2.280 2.003 1.982 1.963 1.949 1.924 1.377 1.353 1.261 0.901 0.880 0.857 -0.000

7.263

11.037

PPM

Supplementary Figure 18. 13C NMR (75 MHz, CDCl3) spectrum for (Ra)-5c.

94

179.948

203.654

200

2015-07-04 16:56:15.515 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 154 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz

150

zj-4-033

100

50

33.137 31.914 29.644 29.469 29.350 29.157 29.111 28.826 23.458 22.667 14.064

92.837 89.198 77.423 77.000 76.577

0

PPM

Supplementary Figure 19. 1H NMR (300 MHz, CDCl3) spectrum for (Ra)-4bc.

95

10

7.272

8

2015-10-07 16:54:12.859 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz

6

5.167 5.152 5.148 5.135 5.126 5.120 5.115 5.106 4.167 4.144 4.120 4.096 2.00

zj-4-111

4

2.00 2.00

2.02

2

2.00

21.83

3.05

0

2.441 2.435 2.418 2.414 2.409 2.391 2.388 2.332 2.316 2.307 2.300 2.289 2.279 2.276 2.267 2.249 2.002 1.979 1.963 1.954 1.947 1.922 1.373 1.352 1.283 1.259 1.235 0.902 0.881 0.858 -0.000

PPM

Supplementary Figure 20. 13C NMR (75 MHz, CDCl3) spectrum for (Ra)-4bc.

96

173.146

203.645

200

2015-10-07 17:16:27.390 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 359 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz

150

zj-4-111

100

50

33.449 31.887 29.635 29.607 29.451 29.322 29.129 28.862 23.880 22.649 14.192 14.073

60.243

77.423 77.000 76.577

92.507 89.473

0

PPM

zj-4-111-od-h-100-0-0.7-214 实验时间:2015-10-13,9:01:11 谱图文件:D:\zhuguangjiong\zj\20151010\zj-4-111-od-h-100-00.7-214.org

报告时间:2015-10-13,10:14:25

实验内容简介:

色谱图(zj-4-111-od-h-100-0-0.7-214.org)

1,500 1,400 1,300 1,200 1,100 1,000

电压(mv)

900 800 700 600

14.175

500 400 300

13.918

200 100 0 0

1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

16

17

时间(min)

峰号 1 2

峰名

保留时间

分析结果表 峰高

13.918 14.175

12605.106 322828.813 335433.919

总计

Supplementary Figure 21. HPLC spectrum for (Ra)-4bc. 97

峰面积

含量

135971.844 8508424.000

1.5729 98.4271

8644395.844

100.0000

zj-4-110-od-h-100-0-0.7-214 实验时间:2015-10-13,9:39:25 谱图文件:D:\zhuguangjiong\zj\20151010\zj-4-110-od-h-100-00.7-214...org

报告时间:2015-10-13,10:12:11

实验内容简介:

色谱图(zj-4-110-od-h-100-0-0.7-214...org)

500 450 400 350

电压(mv)

300 250 200

13.877 14.487

150 100 50 0 0

1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

16

17

18

19

20

时间(min)

峰号 1 2

峰名

保留时间

分析结果表 峰高

13.877 14.487

总计

Supplementary Figure 22. HPLC spectrum for rac-4bc. 98

峰面积

含量

87863.875 79448.938

1429751.875 1442813.875

49.7726 50.2274

167312.813

2872565.750

100.0000

Supplementary Figure 23. 1H NMR (300 MHz, CDCl3) spectrum for (Ra)-4bd.

99

10

7.319

8

2017-05-18 15:26:16.375 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz

6

5.243 5.223 5.203 5.192 5.176 5.158 5.148 5.137 5.126 4.165 4.141 4.117 4.093 1.95

4

2.00

zj-8-048

2.00

3.01

2

3.08

0

2.438 2.432 2.411 2.388 2.338 2.334 2.327 2.323 2.319 2.316 2.306 2.294 2.289 2.281 2.273 2.269 2.267 2.258 2.255 2.248 2.236 2.225 1.281 1.257 1.233 1.005 0.982 -0.000

PPM

Supplementary Figure 24. 13C NMR (75 MHz, CDCl3) spectrum for (Ra)-4bd.

100

202.000

200

172.944

2017-05-18 15:39:59.125 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 217 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz

150

zj-8-048

99.805

100

50

14.064

27.750 23.789 22.290 22.235

33.265

60.096

77.423 77.000 76.577

90.687

0

PPM

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Supplementary Figure 25. HPLC spectrum for (Ra)-4bd. 101

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Supplementary Figure 26. HPLC spectrum for rac-4bd.

102

103

12

Supplementary Figure 27. 1H NMR (300 MHz, CDCl3) spectrum for (Ra)-5d.

10.896

10

0.83

2017-05-22 10:20:47.734 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz

8

6

5.247 5.237 5.227 5.218 5.206 5.187 5.175 5.166 2.00

zj-8-051

4

2.00

2

3.00

2.508 2.484 2.460 2.348 2.336 2.328 2.317 2.307 2.289 2.273 2.251 2.233 1.004 0.981 6.01

0

0.000

7.269

PPM

Supplementary Figure 28. 13C NMR (75 MHz, CDCl3) spectrum for (Ra)-5d.

104

179.856

202.082

200

2017-05-22 14:05:49.140 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 880 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz

150

zj-8-051

100.274

100

50

27.861 23.522 22.364 22.318

33.109

77.423 77.000 76.577

90.503

0

PPM

105

10

Supplementary Figure 29. 1H NMR (300 MHz, CDCl3) spectrum for (Ra)-4bd.

7.295

8

2017-08-26 13:16:16.140 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz

6

1.97

4

2.00

zj-8-063

2.02

3.02

2

3.01

6.07

5.243 5.232 5.223 5.213 5.203 5.197 5.191 5.186 5.178 5.172 5.168 5.159 5.153 5.149 5.139 5.133 5.128 4.166 4.142 4.118 4.094 2.434 2.412 2.386 2.334 2.314 2.301 2.283 2.268 2.256 2.250 2.226 2.216 2.204 1.281 1.258 1.234 1.003 0.980 -0.000

0

PPM

Supplementary Figure 30. 13C NMR (75 MHz, CDCl3) spectrum for (Ra)-4bd.

106

202.055

200

173.064

150

2017-08-26 13:38:39.093 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 355 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz zj-8-063

99.878

100

50

14.119

27.805 23.862 22.355 22.299

33.348

60.179

77.423 77.000 76.577

90.742

0

PPM

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Supplementary Figure 31. HPLC spectrum for (Ra)-4bd. 107

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Supplementary Figure 32. HPLC spectrum for rac-4bd.

108

109

12

Supplementary Figure 33. 1H NMR (300 MHz, CDCl3) spectrum for (Ra)-5e.

11.177

10

0.98

2015-06-10 23:22:36.452 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz

5.234 5.204 5.194 7.270 5.184 5.153 5.142 5.121

8

6

1.97

zj-3-196

4

2.00

2.00

2

1.00

5.00

5.12

0

-2

2.504 2.501 2.479 2.455 2.336 2.325 2.317 2.306 2.295 2.284 2.280 2.273 2.261 1.990 1.971 1.953 1.942 1.923 1.905 1.886 1.752 1.737 1.725 1.715 1.705 1.683 1.647 1.607 1.323 1.295 1.282 1.241 1.201 1.164 1.125 1.074 1.036 0.993 -0.000

PPM

Supplementary Figure 34. 13C NMR (75 MHz, CDCl3) spectrum for (Ra)-5e.

110

179.985

202.413

200

2015-06-11 12:08:23.125 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 222 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz

150

zj-3-196

98.867

100

50

37.144 33.091 32.934 26.068 25.985 23.467

77.423 77.000 76.577

90.126

0

PPM

111

10

Supplementary Figure 35. 1H NMR (300 MHz, CDCl3) spectrum for (Ra)-4be.

7.292

8

2015-06-16 11:12:04.390 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz

6

5.222 5.192 5.182 5.172 5.163 5.145 5.125 5.115 5.094 4.164 4.140 4.117 4.093 1.95

4

2.00

zj-4-006

2.00 2.00

2

1.03

5.02

8.25

0

PPM

2.439 2.411 2.388 2.329 2.300 2.287 2.276 2.260 1.995 1.964 1.948 1.919 1.901 1.881 1.742 1.717 1.689 1.648 1.611 1.327 1.284 1.260 1.236 1.206 1.169 1.121 1.073 1.035 0.994 0.000

Supplementary Figure 36. 13C NMR (75 MHz, CDCl3) spectrum for (Ra)-4be.

112

202.386

200

173.082

2015-06-16 13:32:30.034 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 183 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz

150

98.490

100

zj-4-006

50

14.137

37.108 33.330 32.953 32.916 26.059 25.958 23.825

60.188

77.432 77.000 76.577

90.365

0 PPM

zj-4-006-ay-100-0-0.6-214 实验时间:2015/7/9,12:05:37 报告时间:2015/7/9,18:01:10 谱图文件:D:\zhuguangjiong\zj\20150706\zj-4-006-ay-100-0-0.6214..org 实验内容简介:

色谱图(zj-4-006-ay-100-0-0.6-214..org)

500 450 400 350

250 200

17.317

电压(mv)

300

150 100 50 0 0

1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

16

17

18

19

20

21

22

时间(min)

峰号 1 2

峰名

保留时间

分析结果表 峰高

17.317 17.317

总计

Supplementary Figure 37. HPLC spectrum for (Ra)-4be. 113

峰面积

含量

107960.531 2235.882

5137819.000 87625.016

98.3231 1.6769

110196.414

5225444.016

100.0000

zj-4-005-ay-100-0-0.6-214 实验时间:2015/7/9,11:06:55 报告时间:2015/7/9,17:59:35 谱图文件:D:\zhuguangjiong\zj\20150706\zj-4-005-ay-100-0-0.6214.org

0

1

2

3

4

5

6

7

8

9

19.367

色谱图(zj-4-005-ay-100-0-0.6-214.org)

200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0

17.743

电压(mv)

实验内容简介:

10 11 12 13 14 15 16 17 18 19 20 21 22 23 24

时间(min)

峰号 1 2

峰名

保留时间

分析结果表 峰高

17.743 19.367

总计

Supplementary Figure 38. HPLC spectrum for rac-4be. 114

峰面积

含量

64498.359 53120.230

2592152.750 2621561.000

49.7180 50.2820

117618.590

5213713.750

100.0000

Supplementary Figure 39. 1H NMR (300 MHz, CDCl3) spectrum for (Ra)-5f.

115

12

10

1.00

2015-11-07 13:17:18.703 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz

8

7.303 7.289 7.278 7.276 7.266 7.255 7.207 7.196 7.184 2.03

3.02

6

5.333 5.331 5.321 5.310 5.299 5.204 5.194 5.185 5.174 5.165 1.01 1.00

zj-4-169

3.328 3.319 3.305 3.296

4

2.01 2.03

2

2.443 2.439 2.416 2.393 2.309 2.299 2.288 2.278 2.267 2.256

2.00

0

0.000

10.530

PPM

Supplementary Figure 40. 13C NMR (75 MHz, CDCl3) spectrum for (Ra)-5f.

116

179.679

204.236

200

2015-11-08 22:25:21.351 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 311 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz

150

zj-4-169

100

50

23.363

35.522 33.041

77.423 77.000 76.577

92.192 89.858

128.404 128.303 126.106

140.149

0

PPM

117

Supplementary Figure 41. 1H NMR (300 MHz, CDCl3) spectrum for (Ra)-4bf. 10 8

2015-11-11 09:52:06.906 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz

2.01

2.96

7.305 7.301 7.280 7.277 7.273 7.261 7.253 7.210 7.187 7.180 7.151

6 0.96

0.98

4

2.00

zj-4-174

2.00 4.01

2 3.01

5.338 5.328 5.318 5.307 5.294 5.283 5.273 5.260 5.250 5.221 5.213 5.202 5.192 5.182 5.172 5.162 5.152 5.143 4.138 4.114 4.090 4.066 3.329 3.319 3.305 3.296 2.399 2.391 2.378 2.370 2.346 2.318 2.305 2.296 2.286 2.275 2.265 2.255 2.243 2.236 1.250 1.226 1.202 -0.000

0 PPM

Supplementary Figure 42. 13C NMR (75 MHz, CDCl3) spectrum for (Ra)-4bf.

118

172.852

204.178

200

2015-11-11 09:58:27.718 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 83 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz

150

zj-4-174

100

50

14.082

23.678

35.536 33.229

60.133

77.423 77.000 76.577

91.734 90.025

128.309 128.208 126.002

140.148

0 PPM

zj-4-174-as-h-100-0-1-214 实验时间:2015/11/17,11:15:06 报告时间:2015/11/17,16:56:02 谱图文件:D:\zhuguangjiong\zj\20151117\zj-4-174-as-h-100-0-1214..org 实验内容简介:

1,500

色谱图(zj-4-174-as-h-100-0-1-214..org)

1,400 1,300 1,200 1,100 1,000

800 700

20.277

电压(mv)

900

600 500 400 300

23.315

200 100

0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34

时间(min)

峰号 1 2

峰名

保留时间

分析结果表 峰高

20.277 23.315

总计

Supplementary Figure 43. HPLC spectrum for (Ra)-4bf. 119

峰面积

含量

430079.688 11803.181

33621564.000 772857.188

97.7530 2.2470

441882.868

34394421.188

100.0000

zj-4-021-as-h-100-0-1-214 实验时间:2015/11/17,10:10:53 报告时间:2015/11/17,16:54:51 谱图文件:D:\zhuguangjiong\zj\20151117\zj-4-021-as-h-100-0-1214.org 实验内容简介:

1,500

色谱图(zj-4-021-as-h-100-0-1-214.org)

1,400 1,300 1,200 1,100 1,000

电压(mv)

900 800 700 600

400 300

23.115

20.907

500

200 100 0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31

时间(min)

峰号 1 2

峰名

保留时间

分析结果表 峰高

20.907 23.115

总计

Supplementary Figure 44. HPLC spectrum for rac-4bf. 120

峰面积

含量

269109.406 233418.578

19191692.000 19284672.000

49.8792 50.1208

502527.984

38476364.000

100.0000

Supplementary Figure 45. 1H NMR (300 MHz, CDCl3) spectrum for (Ra)-5g.

121

11.146

12

2015-10-21 10:30:39.296 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz

10

0.82

8

7.293 7.269 7.244 7.190 7.166 7.142 2.00

3.02

6

1.98

5.233 5.224 5.213 5.191 5.180 5.160 5.150 5.131

zj-4-139

4

2.00

2

6.13

2.726 2.700 2.674 2.379 2.370 2.351 2.327 2.315 2.304 2.294 2.283 2.260 2.249 2.241 2.230 2.219 2.207 2.178 -0.000

0

PPM

Supplementary Figure 46. 13C NMR (75 MHz, CDCl3) spectrum for (Ra)-5g.

122

179.737

203.792

200

2015-10-24 22:30:17.984 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 165 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz

150

zj-4-139

100

50

23.329

35.196 32.916 30.425

77.423 77.000 76.577

92.075 89.823

128.456 128.244 125.818

141.664

0

PPM

123

Supplementary Figure 47. 1H NMR (300 MHz, CDCl3) spectrum for (Ra)-4bg. 10 8

2015-10-21 10:37:43.515 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz

2.07

2.95

7.294 7.288 7.282 7.270 7.267 7.254 7.246 7.233 7.221 7.192 7.167 7.156 7.141

6

5.211 5.202 5.191 5.182 5.170 5.164 5.160 5.149 5.142 5.131 5.121 4.154 4.130 4.106 4.082

1.96

zj-4-141

4

2.00 2.00

2.728 2.702 2.677 2.383 2.360 2.348 2.337 2.329 2.323 2.316 2.306 2.292 2.267 2.258 2.251 2.239 2.231 2.221 2.209 1.269 1.245 1.221 0.000

6.07

2 3.05

0 PPM

Supplementary Figure 48. 13C NMR (75 MHz, CDCl3) spectrum for (Ra)-4bg.

124

203.774

200

2015-10-22 13:54:41.296 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 142 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz

150

zj-4-141

100

50

14.156

23.706

35.214 33.256 30.425

60.179

77.423 77.000 76.577

91.661 90.062

128.401 128.198 125.753

141.646

172.999

0

PPM

zj-4-141-as-h-100-0-0.7-214 实验时间:2015-11-04,12:42:36 谱图文件:D:\zhuguangjiong\zj\20151103\zj-4-141-as-h-100-00.7-214...org

报告时间:2015-11-04,13:53:04

实验内容简介:

色谱图(zj-4-141-as-h-100-0-0.7-214...org) 2,400 2,200 2,000 1,800

1,400 1,200

18.495

电压(mv)

1,600

1,000 800 600

22.813

400 200

0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35

时间(min)

峰号 1 2

峰名

保留时间

分析结果表 峰高

18.495 22.813

总计

Supplementary Figure 49. HPLC spectrum for (Ra)-4bg. 125

峰面积

含量

793333.813 19756.412

66945280.000 1418243.375

97.9254 2.0746

813090.225

68363523.375

100.0000

zj-4-142-as-h-100-0-0.7-214 实验时间:2015-11-04,10:35:23 谱图文件:d:\zhuguangjiong\zj\20151103\zj-4-142-as-h-100-00.7-214.org

报告时间:2015-11-04,13:52:18

实验内容简介:

色谱图(zj-4-142-as-h-100-0-0.7-214.org) 2,400 2,200 2,000 1,800

1,400

1,000 800 600

21.897

1,200

19.288

电压(mv)

1,600

400 200 0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35

时间(min)

峰号 1 2

峰名

保留时间

分析结果表 峰高

19.288 21.897

总计

Supplementary Figure 50. HPLC spectrum for rac-4bg. 126

峰面积

含量

642363.875 492664.531

49289944.000 50444076.000

49.4214 50.5786

1135028.406

99734020.000

100.0000

Supplementary Figure 51. 1H NMR (300 MHz, CDCl3) spectrum for (Ra)-5h.

127

10.564

12

10

2016-01-01 11:32:12.406 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz

0.74

8

6

0.98

2.00 2.00

4

zj-5-056

2.00

2.01

2

4.07

12.20

5.878 5.856 5.845 5.834 5.822 5.800 5.788 5.777 5.766 5.743 5.185 5.169 5.154 5.138 5.123 5.021 5.016 4.964 4.946 4.912 2.502 2.479 2.454 2.334 2.319 2.295 2.281 2.258 2.071 2.049 2.026 2.002 1.981 1.963 1.944 1.374 1.352 1.279 -0.000

7.264

0

PPM

Supplementary Figure 52. 13C NMR (75 MHz, CDCl3) spectrum for (Ra)-5h.

128

179.829

203.663

200

2015-12-30 10:28:21.750 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 169 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz

150

100

zj-5-056

50

33.780 33.137 29.432 29.368 29.092 29.074 28.890 28.807 23.476

77.423 77.000 76.577

92.837 89.216

114.080

139.173

0 PPM

Supplementary Figure 53. 1H NMR (300 MHz, CDCl3) spectrum for (Ra)-4bh.

129

7.302

10

2016-01-03 10:31:19.984 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz

8

6

1.00

zj-5-065

2.00

2.00

4

2.00

2.00 2.02

2

4.10

15.28

0

5.865 5.843 5.831 5.821 5.809 5.786 5.774 5.764 5.752 5.730 5.157 5.143 5.126 5.111 5.097 5.012 5.005 4.949 4.936 4.933 4.902 4.158 4.135 4.111 4.087 2.431 2.424 2.403 2.380 2.324 2.309 2.292 2.281 2.268 2.246 2.047 2.022 1.999 1.977 1.961 1.944 1.925 1.378 1.356 1.283 1.274 1.249 1.226 -0.000

PPM

Supplementary Figure 54. 13C NMR (75 MHz, CDCl3) spectrum for (Ra)-4bh.

130

172.861

203.590

200

2016-01-03 10:37:37.781 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 85 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467758 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz

150

113.979

zj-5-065

100

50

33.670 33.320 29.322 29.276 28.982 28.789 28.734 23.779 14.082

60.050

77.423 77.000 76.577

92.304 89.400

138.953

0

PPM

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Supplementary Figure 55. HPLC spectrum for (Ra)-4bh. 131

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Supplementary Figure 56. HPLC spectrum for rac-4bh. 132

Supplementary Figure 57. 1H NMR (300 MHz, CDCl3) spectrum for (Ra)-5i.

133

10.920

10

0.97

2016-07-07 15:35:56.593 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz

8

5.166 5.150 5.134 5.119 5.103

6

zj-6-186

1.97

4

2

2.00 1.98 1.97 2.04

8.07

9.00

0

5.97

PPM

2.478 2.453 2.429 2.314 2.298 2.283 2.275 2.260 2.232 2.224 2.200 2.177 1.991 1.969 1.952 1.935 1.912 1.541 1.520 1.497 1.474 1.395 1.377 1.356 1.338 1.309 1.272 0.906 0.056

7.260

Supplementary Figure 58. 13C NMR (75 MHz, CDCl3) spectrum for (Ra)-5i.

134

179.783

203.654

200

2016-07-07 15:42:25.640 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 80 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz

150

108.059

zj-6-186

100

50

0

-4.495

33.118 28.890 28.688 28.559 28.476 26.013 23.439 19.717 16.444

82.313 77.423 77.000 76.577

92.690 89.271

PPM

Supplementary Figure 59. 1H NMR (300 MHz, CDCl3) spectrum for (Ra)-4bi.

135

10

7.260

8

2016-07-09 16:59:28.984 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz

5.130 5.116 5.101 5.084 5.065

6

4.131 4.107 4.083 4.059 1.95

4

2.00

zj-6-191

2

2.01 2.00 1.99 2.02

3.00

8.03

9.08

0

6.00

2.395 2.378 2.351 2.295 2.292 2.279 2.263 2.251 2.229 2.210 2.187 2.164 1.973 1.951 1.928 1.895 1.509 1.486 1.463 1.440 1.408 1.385 1.363 1.326 1.299 1.246 1.223 1.199 0.892 0.040

PPM

Supplementary Figure 60. 13C NMR (75 MHz, CDCl3) spectrum for (Ra)-4bi.

136

172.990

200

2016-07-09 16:57:29.625 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 215 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz

150

zj-6-191

100

50

0

-4.522

28.899 33.385 28.706 28.550 28.458 25.995 23.825 19.698 16.426 14.174

60.161

77.432 77.000 76.577

92.304 89.528

108.022

203.645

PPM

zj-6-191-oz-h-100-0-1-214 实验时间:2016-07-20,14:32:36 报告时间:2016-07-20,16:37:47 谱图文件:D:\zhuguangjiong\zj\20160719\zj-6-191-oz-h-100-0-1214.....org 实验内容简介:

色谱图(zj-6-191-oz-h-100-0-1-214.....org)

100 90 80 70

电压(mv)

60 50 40

29.112 30.525

30 20 10 0 0

2

4

6

8

10 12 14

16 18 20

22 24 26

28 30 32

34 36 38

40 42 44

时间(min)

峰号 1 2

峰名

保留时间

分析结果表 峰高

29.112 30.525

总计

Supplementary Figure 61. HPLC spectrum for (Ra)-4bi. 137

峰面积

含量

916.083 12404.063

21239.408 1468265.625

1.4259 98.5741

13320.146

1489505.033

100.0000

zj-6-190-oz-h-100-0-1-214 实验时间:2016-07-20,9:47:40 报告时间:2016-07-20,16:39:03 谱图文件:D:\zhuguangjiong\zj\20160719\zj-6-190-oz-h-100-0-1214..org 实验内容简介:

色谱图(zj-6-190-oz-h-100-0-1-214..org)

150 140 130 120 110 100

电压(mv)

90 80 70 60

31.088

50 40

26.985

30 20 10 0 2

4

6

8

10

12

14

16

18

20

22

24

26

28

30

32

34

36

时间(min)

峰号 1 2

峰名

保留时间

分析结果表 峰高

26.985 31.088

总计

Supplementary Figure 62. HPLC spectrum for rac-4bi. 138

峰面积

含量

12032.708 30860.033

1188864.500 1167286.250

50.4579 49.5421

42892.741

2356150.750

100.0000

139

10

Supplementary Figure 63. 1H NMR (300 MHz, CDCl3) spectrum for (Sa)-4bm.

7.299

8

2018-02-02 12:36:50.328 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz

5.166 5.151 5.135 5.119 5.105

6

4.166 4.142 4.118 4.094 1.99

zj-9-055

4

2.00 1.99

2.00

2

2.02

11.51

3.06

0

2.440 2.413 2.409 2.387 2.331 2.310 2.299 2.288 2.275 2.248 2.005 1.982 1.966 1.958 1.950 1.925 1.443 1.427 1.408 1.384 1.359 1.337 1.313 1.282 1.258 1.234 0.907 0.885 0.862 0.000

PPM

Supplementary Figure 64. 13C NMR (75 MHz, CDCl3) spectrum for (Sa)-4bm.

140

200

173.009

150

2018-02-02 12:50:15.218 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 210 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz zj-9-055

100

50

33.348 31.602 29.010 28.789 28.725 23.798 22.548 14.119 13.963

60.142

77.423 77.000 76.577

92.405 89.418

203.590

0

PPM

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Supplementary Figure 65. HPLC spectrum for (Sa)-4bm. 141

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Supplementary Figure 66. HPLC spectrum for rac-4bm. 142

143

10

Supplementary Figure 67. 1H NMR (300 MHz, CDCl3) spectrum for AuCl(LB-Phos).

7.312

8

2017-01-23 13:42:44.984 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz

6

2.00

3.865 3.843

zj-7-180

4

3.00

6.03

2.00

2

2.00

10.65 8.41

0

PPM

2.507 2.468 2.435 2.397 2.077 2.049 2.036 1.842 1.798 1.740 1.715 1.656 1.618 1.589 1.564 1.535 1.523 1.495 1.396 1.355 1.314 1.286 1.262 1.250 1.218 1.191 0.000

6.143 6.133

Supplementary Figure 68. 13C NMR (75 MHz, CDCl3) spectrum for AuCl(LB-Phos).

144

164.506 163.881

200

2017-01-23 14:42:12.859 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 986 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz

150

zj-7-180

93.040 92.304 91.312 91.247

100

50

36.087 35.609 32.263 32.190 29.340 26.748 26.574 26.537 26.326 25.627

55.436 55.362

77.423 77.000 76.577

0

PPM

Supplementary Figure 69. 31P NMR (121.5 MHz, CDCl3) spectrum for AuCl(LB-Phos).

145

200

150

100

2017-01-23 14:58:44.203 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.200 usec Relaxation delay = 2.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 121.494835 MHz F2 = 1.000000 MHz SW1 = 53571.43 Hz

50

31.313

0

zj-7-180-P

-50

-100

-150

-200 PPM

Supplementary Figure 70. 1H NMR (300 MHz, CDCl3) spectrum for (S,E)-6a.

146

7.298

10

2017-05-16 22:34:25.015 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz

8

6

0.02

1.02 0.02

1.00 1.00

4

zj-8-046

1.04

2.04

2

3.11

10.82

3.04

0

5.856 5.834 5.808 5.783 5.760 5.712 5.689 5.681 5.653 5.631 5.527 5.503 5.476 5.452 5.296 5.268 5.246 5.220 4.933 4.909 4.885 4.861 2.565 2.542 2.512 2.431 2.408 2.386 2.366 2.343 2.321 2.095 2.073 2.049 2.025 1.985 1.973 1.946 1.915 1.403 1.381 1.358 1.270 0.902 0.882 0.858 -0.000

PPM

147

Supplementary Figure 71. 1H NMR (300 MHz, CDCl3) extended spectrum for (S,E)-6a. 6.0 5.8

5.856 5.834 5.808 5.783 5.760

1.00

5.6

0.02

5.712 5.689 5.681 5.653 5.631

5.527 5.503 5.476 5.452

5.4

1.02

5.296

5.2

0.02

5.268 5.246 5.220

5.0 4.933 4.909 4.885 4.861 1.00

4.8 4.6 PPM

Supplementary Figure 72. 13C NMR (75 MHz, CDCl3) spectrum for (S,E)-6a.

148

177.007

200

2017-05-16 23:10:55.609 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 582 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz

150

zj-8-046

100

50

31.969 31.648 28.964 28.927 28.715 28.642 28.614 22.502 13.953

81.072 77.423 77.000 76.577

127.233

135.616

0

PPM

m)v(压

zj-8-046-oj-h-200-1-1-214 实验时间:2017-5-24,16:53:49 报告时间:2017-5-24,17:33:30 谱图文件:D:\zhuguangjiong\zj\20170524\zj-8-046-oj-h-200-1-1214..org 实验内容简介:

色谱图(zj-8-046-oj-h-200-1-1-214..org) 2,400 2,200 2,000 1,800

电压(mv)

1,600 1,400 1,200 1,000 22.732

800 600 20.863

400 200 0 0

1 2

3 4

5

6 7

8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30

时间(min)

峰号 1 2

峰名

保留时间

分析结果表 峰高

20.863 22.732

总计

Supplementary Figure 73. HPLC spectrum for (S,E)-6a. 149

峰面积

含量

16647.076 420144.281

395363.438 20229394.000

1.9169 98.0831

436791.357

20624757.438

100.0000

m)v(压

zj-8-029-oj-h-200-1-1-214 实验时间:2017-5-24,15:52:47 报告时间:2017-5-24,17:31:23 谱图文件:D:\zhuguangjiong\zj\20170524\zj-8-029-oj-h-200-1-1214..org

色谱图(zj-8-029-oj-h-200-1-1-214..org)

1

2

3

4

5

6

7

8

23.087

400 380 360 340 320 300 280 260 240 220 200 180 160 140 120 100 80 60 40 20 0 0

20.313

电压(mv)

实验内容简介:

9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30

时间(min)

峰号 1 2

峰名

保留时间

分析结果表 峰高

20.313 23.087

总计

Supplementary Figure 74. HPLC spectrum for rac-6a. 150

峰面积

含量

57729.738 49412.555

2545566.250 2546912.000

49.9868 50.0132

107142.293

5092478.250

100.0000

151

Supplementary Figure 75. 1H NMR (300 MHz, CDCl3) spectrum for (S,E)-6b. 7.333

12 10

2016-05-16 16:08:15.750 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz

8 6 0.03 0.03

1.02 1.00 0.99

zj-6-074

4 1.04

2.02

2

3.11 4.11 3.06

0 -2 PPM

5.856 5.854 5.834 5.831 5.809 5.805 5.783 5.780 5.761 5.758 5.710 5.685 5.649 5.624 5.538 5.534 5.528 5.515 5.510 5.505 5.487 5.482 5.478 5.463 5.459 5.454 5.297 5.268 5.250 5.221 4.931 4.907 4.884 4.860 2.558 2.534 2.526 2.504 2.432 2.410 2.388 2.368 2.345 2.323 2.104 2.082 2.060 2.041 2.034 2.012 2.000 1.986 1.970 1.943 1.912 1.404 1.394 1.381 1.365 1.353 1.342 1.330 1.309 1.285 0.920 0.897 0.873 0.000

152

Supplementary Figure 76. 1H NMR (300 MHz, CDCl3) extended spectrum for (S,E)-6b. 6.0 5.8

5.856 5.854 5.834 5.831 5.809 5.805 5.783 5.780 5.761 5.758 5.710 5.685 5.649

1.00

5.6

0.03

5.624

5.4

1.02

5.538 5.534 5.528 5.515 5.510 5.505 5.487 5.482 5.478 5.463 5.459 5.454

5.297 5.268 5.250

5.2

0.03

5.221

5.0 4.931 4.907 4.884 4.860 0.99

4.8 PPM

Supplementary Figure 77. 13C NMR (75 MHz, CDCl3) spectrum for (S,E)-6b.

153

176.869

200

2016-05-16 16:35:32.234 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 444 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz

150

zj-6-074

100

50

13.613

31.510 30.682 28.605 28.476 21.886

80.916 77.432 77.000 76.577

127.270

135.331

0

PPM

zj-6-074-oj-h-200-1-1-214 实验时间:2016-05-31,12:17:54 报告时间:2016-05-31,17:14:56 谱图文件:D:\zhuguangjiong\zj\20160531\zj-6-074-oj-h-200-1-1214.org

色谱图(zj-6-074-oj-h-200-1-1-214.org)

29.033

200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0

26.333

电压(mv)

实验内容简介:

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40

时间(min)

峰号 1 2

峰名

保留时间

分析结果表 峰高

26.333 29.033

总计

Supplementary Figure 78. HPLC spectrum for (S,E)-6b. 154

峰面积

含量

1418.779 27742.568

39042.988 2190942.750

1.7508 98.2492

29161.348

2229985.738

100.0000

zj-6-056-oj-h-200-1-1-214 实验时间:2016-05-31,14:08:40 报告时间:2016-05-31,17:13:13 谱图文件:D:\zhuguangjiong\zj\20160531\zj-6-056-oj-h-200-1-1214..org

色谱图(zj-6-056-oj-h-200-1-1-214..org)

29.003

200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0

24.948

电压(mv)

实验内容简介:

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35

时间(min)

峰号 1 2

峰名

保留时间

分析结果表 峰高

24.948 29.003

总计

Supplementary Figure 79. HPLC spectrum for rac-6b. 155

峰面积

含量

23389.479 18196.986

1017822.750 1028969.125

49.7277 50.2723

41586.465

2046791.875

100.0000

156

Supplementary Figure 80. 1H NMR (300 MHz, CDCl3) spectrum for (S,E)-6c. 10 8

2015-10-09 20:16:11.078 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz

7.294

6 0.03

1.00 1.01 0.02 1.00

4 zj-4-114

1.08

2.03

2

3.28 19.65

3.08

0

5.856 5.834 5.805 5.783 5.760 5.713 5.688 5.678 5.652 5.627 5.526 5.502 5.474 5.451 5.294 5.265 5.243 5.215 4.931 4.906 4.882 4.859 2.563 2.541 2.536 2.531 2.509 2.426 2.404 2.384 2.362 2.339 2.316 2.134 2.111 2.094 2.071 2.049 2.026 2.012 1.999 1.985 1.970 1.954 1.942 1.912 1.403 1.381 1.357 1.261 0.902 0.880 0.858 0.000

PPM

157

Supplementary Figure 81. 1H NMR (300 MHz, CDCl3) extended spectrum for (S,E)-6c. 5.856 5.834

5.8 1.00

5.805 5.783 5.760 5.713 5.688 5.678 5.652

5.6

0.03

5.627

1.01

5.4

5.526 5.522 5.502 5.498 5.474 5.471 5.455 5.451 5.447

5.294 5.265 5.243

5.2

0.02

5.215

5.0 4.931 4.906 4.882 4.859 1.00

4.8 PPM

Supplementary Figure 82. 13C NMR (75 MHz, CDCl3) spectrum for (S,E)-6c.

158

200

177.007

2015-10-09 20:30:12.593 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 222 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz

150

zj-4-114

100

50

31.978 31.795 29.533 29.506 29.451 29.322 29.221 29.000 28.725 28.660 28.614 22.557 13.990

81.063 76.568

77.423 77.000

127.242

135.616

0 PPM

zj-4-114-as-h-95-5-1-214 实验时间:2015-10-12,14:36:42 谱图文件:D:\zhuguangjiong\zj\20151010\zj-4-114-as-h-95-5-1214..org

报告时间:2015-10-13,17:39:52

实验内容简介:

色谱图(zj-4-114-as-h-95-5-1-214..org)

500 450 400 350

电压(mv)

300 250 200

7.285

150

6.695

100 50 0 0

1

2

3

4

5

6

7

8

9

10

11

12

13

时间(min)

峰号 1 2

峰名

保留时间

分析结果表 峰高

6.695 7.285

总计

Supplementary Figure 83. HPLC spectrum for (S,E)-6c. 159

峰面积

含量

4003.269 84500.078

40812.492 2221214.250

1.8042 98.1958

88503.347

2262026.742

100.0000

zj-4-113-as-h-95-5-1-214 实验时间:2015-10-12,15:35:07 谱图文件:D:\zhuguangjiong\zj\20151010\zj-4-113-as-h-95-5-1214....org

报告时间:2015-10-13,17:38:42

实验内容简介:

色谱图(zj-4-113-as-h-95-5-1-214....org)

500 450 400 350

电压(mv)

300 250 200

100

7.383

6.487

150

50 0 0

1

2

3

4

5

6

7

8

9

10

11

12

13

14

时间(min)

峰号 1 2

峰名

保留时间

分析结果表 峰高

6.487 7.383

总计

Supplementary Figure 84. HPLC spectrum for rac-6c. 160

峰面积

含量

47584.324 36512.277

661526.563 671442.813

49.6280 50.3720

84096.602

1332969.375

100.0000

161

Supplementary Figure 85. 1H NMR (300 MHz, CDCl3) spectrum for (S,E)-6d. 10 8

2017-06-15 23:01:01.218 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz

7.312

6

5.827 5.824 5.805 5.802 5.775 5.773 5.754 5.751 5.486 5.481 5.462 5.457 5.434 5.430 5.410 5.406 5.371 5.340 5.308 5.283 5.267 4.936 4.912 4.888 4.864 2.575 2.549 2.543 2.519 2.462 2.439 2.417 2.397 2.375 2.352 2.345 2.318 2.300 2.273 2.051 2.022 2.010 1.995 1.980 1.964 1.953 1.922 1.021 0.998 -0.000

1.00 1.03 1.00

4

zj-8-058

2.01 2.04

2

1.23 6.04

0 PPM

Supplementary Figure 86. 13C NMR (75 MHz, CDCl3) spectrum for (S,E)-6d.

162

200

141.968

176.933

150

2017-06-10 23:44:33.015 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 153 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz

100

zj-8-058

50

30.352 28.578 28.467 21.638

81.017 77.432 77.000 76.577

124.384

0

PPM

Supplementary Figure 87. Quantitative 13C NMR (75 MHz, CDCl3) spectrum for (S,E)-6d.

163

200

142.619 142.040

176.996

150

1.06 0.02

0.01

124.659 124.355

1.00

2017-06-11 08:40:34.751 USER: nmr SOLVENT: CDCl3 Experiment = zgig30 Pulse length = 9.500 usec Relaxation delay = 60.000 sec NA = 600 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz

100

zj-8-058-Q

50

21.657

30.380 28.606 28.514

81.090 77.432 77.000 76.577

0

PPM

PPM 1.00

140

135

130

0.02

125

1.06

124.659 124.355

0.01

142.040 142.619

Supplementary Figure 88. Quantitative 13C NMR (75 MHz, CDCl3) extended spectrum for (S,E)-6d. 164

zj-8-058-as-h-98-2-1-210 实验时间:2017-06-16,16:50:01 谱图文件:D:\zhuguangjiong\zj\20170616\zj-8-058-as-h-98-2-1214..org

报告时间:2017-06-16,18:08:14

实验内容简介:

500

色谱图(zj-8-058-as-h-98-2-1-214..org)

450 400 350

电压(mv)

300 250 200

21.268

100 50

23.628

150

0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40

时间(min)

峰号 1 2

峰名

保留时间

分析结果表 峰高

21.268 23.628

总计

Supplementary Figure 89. HPLC spectrum for (S,E)-6d.

165

峰面积

含量

1837.642 54305.750

79774.930 7255602.500

1.0875 98.9125

56143.392

7335377.430

100.0000

zj-8-054-as-h-98-2-1-210 实验时间:2017-06-16,17:31:45 谱图文件:D:\zhuguangjiong\zj\20170616\zj-8-054-as-h-98-2-1214..org

报告时间:2017-06-16,18:09:54

色谱图(zj-8-054-as-h-98-2-1-214..org)

24.585

400 380 360 340 320 300 280 260 240 220 200 180 160 140 120 100 80 60 40 20 0

20.092

电压(mv)

实验内容简介:

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31

时间(min)

峰号 1 2

峰名

保留时间

分析结果表 峰高

20.092 24.585

总计

Supplementary Figure 90. HPLC spectrum for rac-6d. 166

峰面积

含量

39390.332 28990.822

2938623.000 2957957.000

49.8361 50.1639

68381.154

5896580.000

100.0000

167

Supplementary Figure 91. 1H NMR (300 MHz, CDCl3) spectrum for (S,E)-6e. 7.347

10 8

2015-07-13 22:02:51.265 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz

6 1.00

zj-4-008

1.01 0.99

4 1.02

1.99

2

2.02 5.00 5.16

0 -2

5.792 5.790 5.770 5.768 5.741 5.738 5.719 5.716 5.482 5.478 5.458 5.454 5.430 5.426 5.406 5.402 4.923 4.899 4.875 4.852 2.562 2.560 2.538 2.530 2.508 2.432 2.411 2.390 2.368 2.346 2.037 2.012 2.009 2.002 1.997 1.981 1.976 1.970 1.966 1.951 1.939 1.934 1.747 1.742 1.737 1.703 1.673 1.642 1.637 1.633 1.292 1.283 1.258 1.251 1.243 1.219 1.204 1.165 1.126 1.087 1.055 0.000

PPM

Supplementary Figure 92. 13C NMR (75 MHz, CDCl3) spectrum for (S,E)-6e.

168

200

176.584

2015-06-16 21:23:19.296 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 112 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz

150

zj-4-008

100

50

31.887 31.850 28.302 28.155 25.471 25.296

39.562

80.778 77.432 77.000 76.577

124.650

140.295

0 PPM

Supplementary Figure 93. Quantitative 13C NMR (75 MHz, CDCl3) spectrum for (S,E)-6e.

169

200

140.762 140.303

150

1.00

0.01

0.02

124.999 124.631

0.96

2015-06-17 09:16:54.125 USER: nmr SOLVENT: CDCl3 Experiment = zgig30 Pulse length = 9.500 usec Relaxation delay = 60.000 sec NA = 612 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz

100

zj-4-008-Q

0.01

80.796 77.432 77.000 76.577 0.97

50

31.869 31.832 28.294 28.156 25.462 25.288

39.562

176.610

0

PPM

PPM 1.00

0.01

124.631

0.96

140

138

136

134

132

130

128

126

124.999

0.02

140.303 140.762

Supplementary Figure 94. Quantitative 13C NMR (75 MHz, CDCl3) extended spectrum for (S,E)-6e. 170

zj-4-008-oj-h-95-5-1-214 实验时间:2015-07-23,15:56:37 谱图文件:D:\zhuguangjiong\zj\20150720\zj-4-008-oj-h-95-5-1214..org

报告时间:2015-07-23,17:03:34

实验内容简介:

色谱图(zj-4-008-oj-h-95-5-1-214..org)

300 280 260 240 220 200

电压(mv)

180 160 140 120 100

17.053

80 60

13.228

40 20 0 0

1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

16

17

18

19

20

21

时间(min)

峰号 1 2

峰名

保留时间

分析结果表 峰高

13.228 17.053

总计

Supplementary Figure 95. HPLC spectrum for (S,E)-6e. 171

峰面积

含量

1296.325 45912.770

24145.711 1256106.750

1.8860 98.1140

47209.095

1280252.461

100.0000

zj-4-007-oj-h-95-5-1-214 实验时间:2015-07-23,14:50:22 谱图文件:D:\zhuguangjiong\zj\20150720\zj-4-007-oj-h-95-5-1214..org

报告时间:2015-07-23,17:02:36

实验内容简介:

色谱图(zj-4-007-oj-h-95-5-1-214..org)

300 280 260 240 220 200

电压(mv)

180 160 140 120 100

60

16.968

12.760

80

40 20 0 0

1

2

3

4

5

6

7

8

9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30

时间(min)

峰号 1 2

峰名

保留时间

分析结果表 峰高

12.760 16.968

总计

Supplementary Figure 96. HPLC spectrum for rac-6e. 172

峰面积

含量

45605.098 37913.973

983555.813 964117.250

50.4990 49.5010

83519.070

1947673.063

100.0000

173

Supplementary Figure 97. 1H NMR (300 MHz, CDCl3) spectrum for (S,E)-6f. 12 10 8

2015-11-11 20:09:09.156 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz

2.03

2.99

6 0.02 0.02

1.00 1.02

zj-4-175

1.00

4 2.05

2

1.02

2.02

1.01

0 -2 PPM

7.285 7.280 7.275 7.263 7.258 7.253 7.190 7.185 7.173 7.165 7.156 7.146 7.141 7.118 5.947 5.944 5.925 5.922 5.902 5.898 5.897 5.893 5.874 5.871 5.851 5.848 5.798 5.779 5.764 5.753 5.727 5.537 5.533 5.528 5.514 5.509 5.504 5.486 5.481 5.477 5.463 5.458 5.453 5.333 5.304 5.282 5.251 4.858 4.833 4.809 4.786 3.354 3.331 2.422 2.414 2.405 2.391 2.292 2.272 2.270 2.250 2.227 2.204 1.933 1.907 1.903 1.891 1.877 1.872 1.865 1.861 1.846 1.835 1.830 1.803 0.000

174

Supplementary Figure 98. 1H NMR (300 MHz, CDCl3) extended spectrum for (S,E)-6f. zj-4-175

6.0

5.947 5.944 5.925 5.922 5.902 5.898 5.897 5.893 5.874 5.871 5.851 5.848 5.798 5.779 5.764 5.753 5.727 5.537 5.533 5.528 5.514 5.509 5.504 5.486 5.481 5.477 5.463 5.458 5.453 5.333 5.304 5.282 5.251

1.00

0.02

5.5 1.02

0.02

5.0

4.858 4.833 4.809 4.786

1.00

4.5 PPM

Supplementary Figure 99. 13C NMR (75 MHz, CDCl3) spectrum for (S,E)-6f.

175

200

176.581

2015-11-11 20:21:55.875 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 178 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz

150

zj-4-175

100

50

28.151 28.115

37.886

80.195 77.438 77.006 76.583

133.186 128.480 128.140 128.066 125.851

138.757

0

PPM

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Supplementary Figure 100. HPLC spectrum for (S,E)-6f. 176

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Supplementary Figure 101. HPLC spectrum for rac-6f.

177

Supplementary Figure 102. 1H NMR (300 MHz, CDCl178 3) spectrum for (S,E)-6g. 12 10

2015-10-25 14:28:43.140 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz

8 2.08

3.01

6

zj-4-146

1.03

0.03

1.01 0.03

1.00

4 2.07

2.00

1.03

2

3.05

0 -2 PPM

7.292 7.288 7.271 7.265 7.244 7.240 7.191 7.187 7.167 7.161 7.156 7.148 7.134 5.853 5.849 5.831 5.827 5.808 5.805 5.802 5.798 5.779 5.776 5.757 5.754 5.710 5.670 5.659 5.646 5.619 5.514 5.510 5.505 5.491 5.486 5.482 5.463 5.459 5.454 5.440 5.435 5.430 5.093 5.065 5.043 5.014 4.872 4.846 4.823 4.800 2.715 2.689 2.664 2.487 2.485 2.463 2.456 2.433 2.404 2.378 2.353 2.346 2.324 2.304 2.282 2.258 2.235 1.937 1.912 1.896 1.883 1.870 1.866 1.851 1.840 1.835 -0.000

179

Supplementary Figure 103. 1H NMR (300 MHz, CDCl3) extended spectrum for (S,E)-6g. 5.8

5.853 5.849 5.831 5.827 5.808 5.805 5.802 5.798 5.779 5.776 5.757 5.754 5.710 5.670 5.659 5.646 5.619

1.01

5.6

0.03

5.4

1.03

5.514 5.510 5.505 5.491 5.486 5.482 5.463 5.459 5.454 5.440 5.435 5.430

5.2 5.093 5.065 5.043

5.0

0.03

5.014

4.872 4.846

4.8

4.823 4.800 1.00

PPM

Supplementary Figure 104. 13C NMR (75 MHz, CDCl3) spectrum for (S,E)-6g.

180

176.841

200

2015-10-25 20:52:27.250 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 6548 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz

150

zj-4-146

100

50

34.883 33.550 28.430 28.320

80.566 77.423 77.000 76.577

133.861 128.180 128.097 128.042 125.717

141.030

0

PPM

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Supplementary Figure 105. HPLC spectrum for (S,E)-6g. 181

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Supplementary Figure 106. HPLC spectrum for rac-6g. 182

183

Supplementary Figure 107. 1H NMR (300 MHz, CDCl3) spectrum for (S,E)-6h. 10 8

2016-01-13 21:37:28.187 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 5 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz

7.365

6 2.00 1.00 3.00

zj-5-083

4 1.00

2.00

2

5.06 12.42

5.859 5.837 5.821 5.802 5.793 5.780 5.769 5.758 5.746 5.724 5.526 5.502 5.475 5.451 5.254 5.226 5.191 5.007 5.002 4.951 4.945 4.931 4.928 4.894 4.868 4.845 2.539 2.514 2.508 2.484 2.428 2.417 2.396 2.375 2.353 2.331 2.307 2.089 2.067 2.044 2.022 1.997 1.981 1.967 1.951 1.925 1.894 1.376 1.281 0.000

0 PPM

184

200

Supplementary Figure 108. 13C NMR (75 MHz, CDCl3) spectrum for (S,E)-6h.

177.025

150

2016-01-14 00:40:12.750 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 1357 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz

100

zj-5-083

50

33.697 32.006 29.285 29.000 28.816 28.761 28.679 28.651

81.081 77.423 77.000 76.568

114.052

127.288

139.109 135.635

0

PPM

Operator:Administrator Timebase:HPLC Sequence:20151027-DAD

Page 1-1 2016-1-26 2:12 下午

842 ZJ-5-83 ADH 982 214 0.7

Sample Name: Vial Number: Sample Type: Control Program: Quantif. Method: Recording Time: Run Time (min):

120

ZJ-5-83 ADH 982 214 0.7 RD5 unknown test-dad WXL 2016-1-25 10:47 21.00

Injection Volume: Channel: Wavelength: Bandwidth: Dilution Factor: Sample Weight: Sample Amount:

20151027-DAD #842 [modified by Administrator] mAU

9.0 UV_VIS_2 214.0 4 1.0000 1.0000 1.0000 UV_VIS_2 WVL:214 nm

2 - 12.887 100

80

60

40

20 4 - 16.610 1 - 12.087 0

-20 0.0

No. 1 2 3 4 Total:

3 - 14.947

min 2.0

Ret.Time min 12.09 12.89 14.95 16.61

4.0

6.0

Peak Name n.a. n.a. n.a. n.a.

8.0

10.0

12.0

14.0

16.0

Height Area Rel.Area mAU mAU*min % 2.565 0.587 1.65 108.157 32.052 90.05 0.180 0.064 0.18 8.639 2.889 8.12 119.541 35.592 100.00

18.0

Amount n.a. n.a. n.a. n.a. 0.000

21.0

Type BM MB BMB* BMB

Chromeleon (c) Dionex 1996-2006 Version 6.80 SR14 Build 4527 (238909)

defltdad/Integration

Supplementary Figure 109. SFC (supercritical fluid chromatogram) spectrum for (S,E)-6h. 185

Operator:Administrator Timebase:HPLC Sequence:20151027-DAD

Page 1-1 2016-1-26 2:08 下午

841 ZJ-5-82+- ADH 982 214 0.7

Sample Name: Vial Number: Sample Type: Control Program: Quantif. Method: Recording Time: Run Time (min):

35.0

ZJ-5-82+- ADH 982 214 0.7 RE5 unknown test-dad WXL 2016-1-25 10:25 21.00

Injection Volume: Channel: Wavelength: Bandwidth: Dilution Factor: Sample Weight: Sample Amount:

20151027-DAD #841 [modified by Administrator] mAU

9.0 UV_VIS_2 214.0 4 1.0000 1.0000 1.0000 UV_VIS_2 WVL:214 nm

30.0

1 - 11.973 2 - 12.913

25.0

20.0

15.0

10.0

5.0 3 - 15.103 4 - 16.510 0.0

-5.0 0.0

No. 1 2 3 4 Total:

min 2.0

Ret.Time min 11.97 12.91 15.10 16.51

4.0

6.0

Peak Name n.a. n.a. n.a. n.a.

8.0

10.0

12.0

14.0

16.0

Height Area Rel.Area mAU mAU*min % 25.262 6.383 47.00 23.836 6.366 46.88 1.374 0.413 3.04 1.322 0.418 3.08 51.794 13.579 100.00

Amount n.a. n.a. n.a. n.a. 0.000

21.0

Type BM MB BMB BMB

Chromeleon (c) Dionex 1996-2006 Version 6.80 SR14 Build 4527 (238909)

defltdad/Integration

Supplementary Figure 110. SFC spectrum for rac-6h.

18.0

186

187

12

Supplementary Figure 111. 1H NMR (300 MHz, CDCl3) spectrum for (S,E)-6i. 7.260

10 8

2016-07-12 00:01:03.437 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz

6 1.03 1.00 0.03 0.03

1.00

4

zj-6-188

2

2.03 3.09

1.00

1.99 8.32 9.05

0

6.03

-2 PPM

5.829 5.827 5.807 5.805 5.784 5.779 5.756 5.754 5.733 5.732 5.688 5.666 5.650 5.629 5.603 5.509 5.504 5.500 5.486 5.481 5.476 5.458 5.453 5.449 5.435 5.430 5.425 5.262 5.238 5.214 5.186 4.906 4.882 4.858 4.835 2.542 2.511 2.485 2.404 2.382 2.361 2.339 2.316 2.221 2.198 2.175 2.077 2.055 2.033 2.018 1.988 1.976 1.950 1.931 1.920 1.515 1.491 1.467 1.426 1.391 1.376 1.351 1.330 1.300 1.277 0.901 0.051

188

Supplementary Figure 112. 1H NMR (300 MHz, CDCl3) extended spectrum for (S,E)-6i. 6.0 5.8

5.829 5.827 5.807 5.805 5.784 5.779 5.756 5.754 5.733 5.732 5.688 5.666 5.650 5.629 5.603 5.509 5.504 5.500 5.486 5.481 5.476 5.458 5.453 5.449 5.435 5.430 5.425 5.262 5.238 5.214 5.186

1.00

5.6

0.03

5.4

1.03

5.2

0.03

5.0 4.8

1.00

4.906 4.882 4.858 4.835

4.6

zj-6-188

4.4PPM

Supplementary Figure 113. 13C NMR (75 MHz, CDCl3) spectrum for (S,E)-6i.

189

200

176.933

2016-07-11 21:31:34.953 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 580 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz

150

zj-6-188

100

50

0

-4.550

28.706 28.587 31.850 28.495 28.394 28.357 28.320 25.958 19.625 16.380

82.304 80.971 77.423 77.000 76.577

107.921

127.390

135.377

PPM

zj-6-188-oj-h-100-1-0.3-214 实验时间:2016-07-14,12:49:48 谱图文件:D:\zhuguangjiong\zj\20160712\zj-6-188-oj-h-100-10.3-214.org

报告时间:2016-07-14,17:18:57

实验内容简介:

150

色谱图(zj-6-188-oj-h-100-1-0.3-214.org)

140 130 120 110 100

电压(mv)

90 80 70 60

29.487

50 40 30

28.493

20 10 0

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40

时间(min)

峰号 1 2

峰名

保留时间

分析结果表 峰高

28.493 29.487

总计

Supplementary Figure 114. HPLC spectrum for (S,E)-6i. 190

峰面积

含量

883.960 32668.090

26267.666 1786474.625

1.4491 98.5509

33552.050

1812742.291

100.0000

zj-6-182-oj-h-100-1-0.3-214 实验时间:2016-07-14,10:44:07 报告时间:2016-07-14,17:17:55 谱图文件:D:\zhuguangjiong\zj\20160712\zj-6-182-oj-100-1-0.3214.org 实验内容简介:

100

色谱图(zj-6-182-oj-100-1-0.3-214.org)

90 80 70

50 40

28.438

30 20

29.937

电压(mv)

60

10 0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36

时间(min)

峰号 1 2

峰名

保留时间

分析结果表 峰高

28.438 29.937

总计

Supplementary Figure 115. HPLC spectrum for rac-6i. 191

峰面积

含量

13724.570 12299.934

524178.875 521015.469

50.1513 49.8487

26024.504

1045194.344

100.0000

192

Supplementary Figure 116. 1H NMR (300 MHz, CDCl3) spectrum for (R,E)-6j. 7.317

10

2015-11-27 22:27:30.125 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz

8 6 0.03

1.03

0.03

1.01

zj-5-014

1.00

4 1.05

2.00

2

3.05 12.59

3.07

0 PPM

5.856 5.853 5.833 5.831 5.810 5.807 5.805 5.802 5.782 5.780 5.759 5.757 5.703 5.683 5.661 5.647 5.625 5.533 5.528 5.523 5.510 5.505 5.500 5.482 5.478 5.472 5.458 5.454 5.449 5.295 5.273 5.245 5.216 4.929 4.905 4.882 4.858 2.558 2.533 2.527 2.504 2.428 2.406 2.384 2.364 2.341 2.319 2.095 2.072 2.050 2.039 2.024 2.010 1.984 1.942 1.910 1.384 1.359 1.305 1.270 0.904 0.882 0.858 0.000

193

Supplementary Figure 117. 1H NMR (300 MHz, CDCl3) extended spectrum for (R,E)-6j. 6.0 5.8

5.856 5.853 5.833 5.831 5.810 5.807 5.805 5.802 5.782 5.780 5.759 5.757 5.703 5.683 5.661 5.647 5.625 5.533 5.528 5.523 5.510 5.505 5.500 5.482 5.478 5.472 5.458 5.454 5.449 5.295 5.273 5.245 5.216

1.01

5.6

0.03

5.4

1.03

5.2

0.03

5.0 4.929 4.905 4.882 4.858

4.8

1.00

4.6 PPM

Supplementary Figure 118. 13C NMR (75 MHz, CDCl3) spectrum for (R,E)-6j.

194

200

176.869

2015-11-27 22:58:54.234 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 514 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz

150

100

zj-5-014

50

31.905 31.666 29.203 29.037 28.918 28.651 28.596 28.522 22.456 13.889

80.943 77.000 76.577

77.423

127.270

135.442

0

PPM

zj-5-014-oj-h-100-1-1-214 实验时间:2016/1/7,15:21:56 谱图文件:d:\zhuguangjiong\zj\20160106\zj-5-014-oj-100-1-1214..org

报告时间:2016/1/7,17:02:24

实验内容简介:

色谱图(zj-5-014-oj-100-1-1-214..org)

500 450 400 350

250 200 12.928

电压(mv)

300

150

16.147

100 50 0 0

1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

16

17

18

19

20

时间(min)

峰号 1 2

峰名

保留时间

分析结果表 峰高

12.928 16.147

峰面积

含量

120117.664 3762.432

3456854.500 87297.750

97.5368 2.4631

123880.096

3544152.250

100.0000

总计

Supplementary Figure 119. HPLC spectrum for (R,E)-6j. 195

zj-5-013-oj-h-100-1-1-214 实验时间:2016/1/7,13:38:12 谱图文件:d:\zhuguangjiong\zj\20160106\zj-5-013-oj-100-1-1214.org

报告时间:2016/1/7,17:01:04

实验内容简介:

色谱图(zj-5-013-oj-100-1-1-214.org)

500 450 400 350

250 200

15.242

12.720

电压(mv)

300

150 100 50 0 0

1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

16

17

18

19

20

时间(min)

峰号 1 2

峰名

保留时间

分析结果表 峰高

12.720 15.242

总计

Supplementary Figure 120. HPLC spectrum for rac-6j.

196

峰面积

含量

176572.141 146212.047

5660659.000 5765820.000

49.5398 50.4602

322784.188

11426479.000

100.0000

197

Supplementary Figure 121. 1H NMR (300 MHz, CDCl3) spectrum for (S,E)-6b (1.6615 g). 10

2016-06-22 22:49:47.203 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz

7.317

8 6 0.02

1.01

0.02

1.00

zj-6-160

0.99

4 1.01

2.00

2

3.03 4.09 3.03

0 PPM

5.858 5.855 5.835 5.832 5.813 5.809 5.807 5.803 5.784 5.781 5.761 5.759 5.715 5.690 5.676 5.661 5.654 5.537 5.532 5.527 5.513 5.508 5.504 5.486 5.481 5.476 5.462 5.457 5.452 5.296 5.272 5.250 5.222 4.933 4.908 4.885 4.861 2.562 2.536 2.530 2.508 2.431 2.409 2.387 2.367 2.345 2.082 2.061 2.043 2.014 1.987 1.945 1.404 1.381 1.365 1.353 1.342 1.330 1.303 1.279 0.921 0.897 0.873 0.000

198

Supplementary Figure 122. 1H NMR (300 MHz, CDCl3) extended spectrum for (S,E)-6b (1.6615 g). 6.0 5.8

5.858 5.855 5.835 5.832 5.813 5.809 5.807 5.803 5.784 5.781 5.761 5.759 5.715 5.690 5.676 5.661 5.654 5.537 5.532 5.527 5.513 5.508 5.504 5.486 5.481 5.476 5.462 5.457 5.452 5.296 5.272 5.250 5.222

1.00

5.6

0.02

5.4

1.01

5.2

0.02

5.0 0.99

4.933 4.908 4.885 4.861

4.8 4.6 PPM

Supplementary Figure 123. 13C NMR (75 MHz, CDCl3) spectrum for (S,E)-6b (1.6615 g).

199

200

176.933

150

2016-06-22 23:11:36.296 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 348 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz

100

zj-6-160

50

13.659

31.565 30.719 28.651 28.532 21.941

80.971 77.423 77.000 76.568

127.270

135.432

0

PPM

zj-6-160-oj-h-200-1-1-214 实验时间:2016-07-01,10:35:50 报告时间:2016-07-01,12:50:43 谱图文件:D:\zhuguangjiong\zj\20160630\ZJ-6-160-oj-h-200-1-1214.org 实验内容简介:

300

色谱图(ZJ-6-160-oj-h-200-1-1-214.org)

280 260 240 220 200

电压(mv)

180 160 140 120 100

60

23.693

40 20 0

26.387

80

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35

时间(min)

峰号 1 2

峰名

保留时间

分析结果表 峰高

23.693 26.387

总计

峰面积

含量

844.168 27539.016

31765.662 1969061.375

1.5876 98.4124

28383.184

2000827.037

100.0000

Supplementary Figure 124. HPLC spectrum for (S,E)-6b (1.6615 g). 200

zj-6-056-oj-h-200-1-1-214 实验时间:2016-07-01,12:14:25 报告时间:2016-07-01,12:49:09 谱图文件:D:\zhuguangjiong\zj\20160630\ZJ-6-056-oj-h-200-1-1214..org 实验内容简介:

300

色谱图(ZJ-6-056-oj-h-200-1-1-214..org)

280 260 240 220 200

电压(mv)

180 160 140 120 100

22.563

60 40 20

26.498

80

0 -20 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33

时间(min)

峰号 1 2

峰名

保留时间

分析结果表 峰高

22.563 26.498

总计

Supplementary Figure 125. HPLC spectrum for rac-6b. 201

峰面积

含量

21248.332 15297.864

782160.188 785722.813

49.8864 50.1136

36546.196

1567883.000

100.0000

202

Supplementary Figure 126. 1H NMR (300 MHz, CDCl3) spectrum for (R,E)-6m. 10

2018-02-01 13:25:45.546 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz

7.362

8 6 0.03

1.00

0.04

0.97 0.97

zj-9-053

4 1.01

2.00

2

3.01 8.16

3.00

0

5.857 5.834 5.808 5.807 5.783 5.761 5.708 5.678 5.674 5.649 5.624 5.535 5.531 5.527 5.511 5.507 5.503 5.484 5.480 5.476 5.461 5.456 5.452 5.303 5.274 5.250 5.225 4.935 4.911 4.887 4.863 2.561 2.537 2.530 2.506 2.435 2.414 2.392 2.372 2.349 2.326 2.097 2.076 2.053 2.030 2.012 2.000 1.986 1.970 1.944 1.912 1.386 1.364 1.336 1.309 1.282 0.904 0.883 0.860 -0.000

PPM

203

Supplementary Figure 127. 1H NMR (300 MHz, CDCl3) extended spectrum for (R,E)-6m. 6.2 6.0 5.8

5.857 5.834 5.808 5.807 5.783 5.761 5.708 5.678 5.674 5.649 5.624

0.97

5.6

0.04

5.4

1.00

5.535 5.531 5.527 5.511 5.507 5.503 5.484 5.480 5.476 5.461 5.456 5.452 5.303 5.274 5.250 5.225

5.2

0.03

5.0 4.935 4.911 4.887 4.863

4.8

0.97

zj-9-053

4.6 4.4 PPM

Supplementary Figure 128. 13C NMR (75 MHz, CDCl3) spectrum for (R,E)-6m.

204

200

176.823

2018-02-01 14:47:06.468 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 1366 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz

150

100

zj-9-053

50

13.742

31.767 31.317 28.522 28.440 28.412 22.244

80.861 77.423 77.000 76.568

127.169

135.267

0

PPM

zj-9-053-oj-h-97-3-1-214 实验时间:2018-02-02,18:50:03 谱图文件:D:\zhuguangjiong\zj\20180202\zj-9-053-oj-h-973-1-214..org

报告时间:2018-02-02,19:10:10

实验内容简介:

色谱图(zj-9-053-oj-h-97-3-1-214..org)

1,500 1,400 1,300 1,200 1,100 1,000

800 700 600

12.547

电压(mv)

900

500 400

100 0 0

1

2

3

4

5

6

7

8

9

10

11

12

14.537

200

13

14

15.315

12.208

300

15

16

17

18

时间(min)

峰号 1 2 3 4

峰名

保留时间

分析结果表 峰高

12.208 12.547 14.537 15.315

46765.355 381413.406 10995.621 2304.944 441479.326

总计

Supplementary Figure 129. HPLC spectrum for (R,E)-6m. 205

峰面积

含量

516480.156 11254235.000 219209.844 65094.563

4.2844 93.3573 1.8184 0.5400

12055019.563

100.0000

zj-9-054-oj-h-97-3-1-214 实验时间:2018-02-02,18:12:35 谱图文件:D:\zhuguangjiong\zj\20180202\zj-9-054-oj-h-973-1-214..org

报告时间:2018-02-02,18:40:58

色谱图(zj-9-054-oj-h-97-3-1-214..org)

0

13.423

12.115

200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 1

2

3

4

5

6

7

8

9

10

11

12

15.123

12.032

电压(mv)

实验内容简介:

13

14

15

16

17

18

19

时间(min)

峰号 1 2 3 4

峰名

保留时间

分析结果表 峰高

12.032 12.115 13.423 15.123

总计

Supplementary Figure 130. HPLC spectrum for rac-6m. 206

峰面积

含量

6901.926 51452.254 41955.156 2490.805

69434.695 1499887.000 1575010.000 81123.406

2.1527 46.5016 48.8306 2.5151

102800.141

3225455.102

100.0000

207

10

Supplementary Figure 131. 1H NMR (300 MHz, CDCl3) spectrum for rac-8.

7.260

8

2016-11-20 11:33:21.545 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz

6

4.338 4.316 4.299 1.00

4

3.588 3.566 3.544 2.00

zj-7-083

2.684 1.00

0.97

2

1.98

3.99

4.08

9.06

1.715 1.692 1.670 1.654 1.640 1.502 1.487 1.473 1.452 1.421 1.388 1.325 1.302 1.289 0.856 0.012

2.424 2.417

0

5.99

PPM

Supplementary Figure 132. 13C NMR (75 MHz, CDCl3) spectrum for rac-8.

208

200

2016-11-20 12:17:41.562 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 507 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz

150

100

85.061

zj-7-083

50

0

-5.349

32.613 28.954 25.903 25.599 24.938 18.273

37.466

63.176 62.017

77.423 77.000 76.577 72.671

PPM

Supplementary Figure 133. 1H NMR (300 MHz, CDCl3) spectrum for rac-9.

209

7.295

10

8

2016-11-29 10:27:13.221 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz

6

4

1.00

2.00

2.99

3.960 3.954 3.939 3.932 3.917 3.910 3.648 3.626 3.604 3.412 2.458 2.452

zj-7-106

2.00

2

2.00

8.32

0

1.761 1.747 1.739 1.721 1.698 1.676 1.593 1.570 1.547 1.523 1.494 1.472 1.462 1.442 1.428 1.406 1.399 1.381 1.370 1.359 1.347 1.335 -0.000

PPM

Supplementary Figure 134. 13C NMR (75 MHz, CDCl3) spectrum for rac-9.

210

200

2016-11-29 10:44:39.110 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 809 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz

150

zj-7-106

100

50

35.278 32.493 28.973 25.507 24.956

56.337

62.734

77.423 77.000 76.577 73.737 70.970

82.561

0 PPM

Supplementary Figure 135. 1H NMR (300 MHz, CDCl3) spectrum for rac-10.

211

10

9.770 9.764 9.758

0.97

8

2016-12-01 13:58:24.449 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz

6

3.958 3.952 3.937 3.930 3.915 3.909 3.406

zj-7-110

4

1.00

3.00

2.94

2

2.04

2.04

4.03

0

PPM

2.468 2.458 2.452 2.443 2.438 2.419 2.413 1.761 1.750 1.739 1.723 1.717 1.702 1.680 1.656 1.630 1.606 1.541 1.536 1.518 1.504 1.489 1.482 1.476 1.469 1.459 1.438 1.411 1.387 1.364 1.341 1.335 1.318 1.310 0.000

7.300

Supplementary Figure 136. 13C NMR (75 MHz, CDCl3) spectrum for rac-10.

212

201.696

200

2016-12-01 16:11:24.383 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 175 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz

150

100

zj-7-110

50

23.945 21.022

27.897

34.341

42.852

55.528

81.697 77.432 77.000 76.568 73.277 69.968

0 PPM

Supplementary Figure 137. 1H NMR (300 MHz, CDCl3) spectrum for rac-1c.

213

10

7.278

8

2016-12-02 11:03:03.921 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz

1.00

6

4

1.00

3.960 3.953 3.938 3.931 3.917 3.910 3.414

zj-7-112

3.00

0.96

2

2.02 2.02

6.10

0

2.455 2.448 2.137 2.113 2.089 2.065 1.759 1.749 1.737 1.722 1.700 1.685 1.678 1.497 1.487 1.473 1.449 1.422 1.399 1.388 1.377 1.367 1.345 1.331 1.314 0.000

6.408 6.384 6.360

PPM

Supplementary Figure 138. 13C NMR (75 MHz, CDCl3) spectrum for rac-1c.

214

200

2016-12-02 13:34:21.054 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 675 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz

150

zj-7-112

100

50

35.260 32.806 28.614 27.585 24.735

56.420

82.552 77.423 77.000 76.577 73.783 70.878

88.600

138.631

0

PPM

215

10

Supplementary Figure 139. 1H NMR (300 MHz, CDCl3) spectrum for rac-4ck.

8

2016-12-05 21:40:62.118 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz

7.297

6.413 6.405 6.389 6.381 6.365 6.357

1.00

5.315 5.294 5.274 5.252 5.245 5.224 5.204 5.028 5.007 4.997 4.981 4.970 4.960 3.683 3.614 3.592 3.568 3.545 3.323 3.296 2.497 2.469 2.438 2.414 2.384 2.371 2.339 2.328 2.134 2.101 2.086 2.053 1.651 1.634 1.617 1.594 1.564 1.534 1.514 1.491 1.460 1.442 1.420 1.403 1.382 1.351 1.291 -0.000

6 1.00 1.00

zj-7-114

4 1.43 1.02 1.53

3.00 4.01

2

2.00 8.80

0 PPM

Supplementary Figure 140. 13C NMR (75 MHz, CDCl3) spectrum for rac-4ck.

216

173.165

204.178 204.104

200

2016-12-05 22:37:54.162 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 416 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz

150

zj-7-114

90.282 93.315 90.245 88.490 80.254 80.226 77.432 77.000 76.577

100

50

35.618 35.572 33.155 33.072 32.815 28.826 28.771 27.631 25.075 24.993 23.816 23.623

56.033 55.978 51.511

138.686

0 PPM

217

Supplementary Figure 141. 1H NMR (300 MHz, CDCl3) spectrum for rac-5k. 1.00

10

2016-12-08 23:54:03.046 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz

11.231

8

6.410 6.404 6.386 6.380 6.362 6.355 5.330 5.312 5.291

0.97

7.292 5.289 5.263 5.242 5.221 5.054 5.044 5.023 4.996 4.986 3.637 3.616 3.593 3.570 3.331 3.305 2.536 2.512 2.482 2.458 2.396 2.374 2.364 2.351 2.341 2.329 2.319 2.295 2.128 2.122 2.105 2.099 2.080 2.075 2.056 2.050 1.695 1.693 1.659 1.640 1.630 1.607 1.579 1.550 1.521 1.502 1.490 1.478 1.446 1.426 1.403 1.378 1.343 0.000

6

zj-7-121

1.00 1.00

4 1.001.41

1.51

2

2.02 1.97 2.00 8.34

0 -2 PPM

Supplementary Figure 142. 13C NMR (75 MHz, CDCl3) spectrum for rac-5k.

218

178.790

204.242 204.114

200

2016-12-09 17:51:09.364 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 577 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz

150

93.426 93.371 90.126 88.490

100

zj-7-121

50

35.508 35.425 33.118 33.026 32.806 32.778 28.789 28.734 27.603 25.057 24.965 23.494 23.274

55.969 55.877

80.300 77.423 77.000 76.577

138.650

0

PPM

219

Supplementary Figure 143. 1H NMR (300 MHz, CDCl3) spectrum for rac-xestospongiene ((E)-6k). 10 7.393

8

2017-01-06 00:14:09.062 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz

6.416 6.392 6.367

1.00

6 0.01

0.02

2.00

1.00

4

zj-7-158

1.00 3.03 3.07

2

3.02 8.52

0

5.764 5.745 5.712 5.693 5.680 5.659 5.651 5.628 5.607 5.599 5.544 5.514 5.493 5.475 5.338 5.310 5.286 5.263 5.014 4.992 4.970 4.948 3.612 3.592 3.584 3.572 3.542 3.260 2.583 2.557 2.528 2.503 2.487 2.471 2.453 2.435 2.416 2.384 2.124 2.100 2.076 2.052 2.015 1.986 1.944 1.556 1.536 1.509 1.479 1.448 1.426 1.405 1.324 1.253 0.000

PPM

220

Supplementary Figure 144. 1H NMR (300 MHz, CDCl3) extended spectrum for rac-xestospongiene ((E)-6k). 6.5 6.416 6.392 6.367

1.00

6.0 2.00

5.764 5.745 5.712 5.693 5.680 5.659 5.651 5.628 5.607 5.599 5.544 5.514 5.493 5.475

5.5 0.02 0.01

5.338 5.310 5.286 5.263

5.0

5.014 4.992 4.970 4.948

1.00

PPM

Supplementary Figure 145. 13C NMR (75 MHz, CDCl3) spectrum for rac-xestospongiene ((E)-6k).

221

176.437

200

2017-01-07 15:25:24.720 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 213 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467773 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz

150

100

zj-7-158

50

34.653 32.466 28.467 28.348 28.090 28.063 27.236 24.450

56.006

88.113 80.677 80.622 79.583 79.500 77.432 77.000 76.577

138.438 133.925 133.796 129.632 129.403

0

PPM

222 Supplementary Figure 146. Quantitative 13C NMR (75 MHz, CDCl 3) spectrum for rac-xestospongiene ((E)-6k).

176.453

200

2017-01-07 08:43:42.953 USER: nmr SOLVENT: CDCl3 Experiment = zgig30 Pulse length = 9.500 usec Relaxation delay = 60.000 sec NA = 490 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz

150

138.428 133.905 133.777 129.631 129.392 1.00 1.00 0.95 0.92

100

zj-7-158-Q

50

34.645 32.457 28.459 28.339 28.091 28.064 27.227 24.442

55.997

88.094 80.667 80.612 79.592 79.509 77.432 77.000 76.577

0 PPM

129 PPM 1.00 0.92

129.392 0.95

133

132

131

130

129.631 1.00

133.777

134

133.905

Supplementary Figure 147. Quantitative 13C NMR (75 MHz, CDCl3) extended spectrum for racxestospongiene ((E)-6k). 223

Supplementary Figure 148. 1H NMR (300 MHz, CDCl3) spectrum for (S)-11.

224

10

8

2016-12-04 17:33:24.515 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz

6

5.354 5.347 5.332 5.324 5.309 5.302 0.99

4

zj-7-113-1

3.611 3.590 3.568 2.00 0.95

2

2.99 1.99

8.00

8.98

0

5.98

2.447 2.439 1.799 1.775 2.082 1.746 1.724 1.528 1.506 1.462 1.435 1.418 1.375 1.351 1.328 1.314 1.302 0.883 0.038

7.260

PPM

Supplementary Figure 149. 1H NMR (300 MHz, CDCl3) spectrum for (R)-8.

225

10

7.260

8

2016-12-03 20:45:02.354 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz

6

3.604 3.583 3.561

4

1.00

zj-7-113-2

2.00

2

0.96

0.96

1.99

8.08

9.02

0

6.01

1.736 1.725 1.713 1.699 1.682 1.660 1.525 1.502 1.480 1.450 1.440 1.428 1.398 1.344 1.333 1.321 1.308 1.296 0.873 0.028

2.446 2.439 2.244

4.364 4.345 4.325

PPM

Supplementary Figure 150. 13C NMR (75 MHz, CDCl3) spectrum for (R)-8.

226

200

150

2016-12-06 20:51:50.937 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 242 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz

100

63.194 62.192

50

zj-7-113-2

0

-5.313

32.668 28.982 25.939 25.645 24.956 18.329

37.521

77.423 77.000 76.577 72.790

84.988

PPM

Supplementary Figure 151. 1H NMR (300 MHz, CDCl3) spectrum for (R)-11.

227

10

7.260

8

2016-12-05 16:21:48.734 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz

6

5.344 5.336 5.321 5.314 5.299 5.292 1.00

4

2.00

3.601 3.580 3.558

zj-7-117

0.97

2

3.00 2.03

8.02

8.99

0

6.00

2.439 2.431 1.786 1.765 2.069 1.754 1.735 1.713 1.516 1.495 1.473 1.452 1.435 1.408 1.341 1.330 1.319 1.306 1.294 0.873 0.028

PPM

Supplementary Figure 152. 13C NMR (75 MHz, CDCl3) spectrum for (R)-11.

228

200

169.893

2016-12-05 16:55:27.375 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 548 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz

150

zj-7-117

100

50

0

-5.322

34.451 32.640 28.826 25.930 25.572 24.800 20.930 18.310

81.237 77.423 77.000 76.577 73.378 63.727 63.111

PPM

Data File C:\CHEM32\1\DATA\SIG10189.D Sample Name: 7-117 ===================================================================== Acq. Operator : Acq. Instrument : Instrument 1 Location : Vial 1 Injection Date : 12/13/2016 10:18:05 AM Inj Volume : Manually Acq. Method : C:\CHEM32\1\METHODS\DEF_GC.M Last changed : 12/13/2016 10:18:04 AM (modified after loading) Analysis Method : C:\CHEM32\1\METHODS\DEF_GC.M Last changed : 12/13/2016 2:19:39 PM (modified after loading) Sample Info : dexcb

FID1 A, Front Signal (SIG10189.D) pA 900

800

700

600

55.938

500

400

300

200

100

0 0

10

20

30

40

min

50

===================================================================== Area Percent Report ===================================================================== Sorted By : Signal Multiplier: : 1.0000 Dilution: : 1.0000 Use Multiplier & Dilution Factor with ISTDs

Signal 1: FID1 A, Front Signal Peak RetTime Type Width Area Height Area # [min] [min] [pA*s] [pA] % ----|-------|----|-------|----------|----------|--------| 1 55.938 BB 0.0854 1869.97827 310.96283 1.000e2 Totals :

1869.97827

310.96283

Supplementary Figure 153. GC spectrum for (R)-11. Instrument 1 12/13/2016 2:19:42 PM

229

Page

1 of 2

Data File C:\CHEM32\1\DATA\SIG10188.D Sample Name: 7-111-rac ===================================================================== Acq. Operator : Acq. Instrument : Instrument 1 Location : Vial 1 Injection Date : 12/13/2016 9:09:27 AM Inj Volume : Manually Acq. Method : C:\CHEM32\1\METHODS\DEF_GC.M Last changed : 12/13/2016 9:09:26 AM (modified after loading) Analysis Method : C:\CHEM32\1\METHODS\DEF_GC.M Last changed : 12/13/2016 2:18:41 PM (modified after loading) Sample Info : dexcb

FID1 A, Front Signal (SIG10188.D) pA 900

800

700

600

500

400

55.911 56.320

300

200

100

0 0

10

20

30

40

min

50

===================================================================== Area Percent Report ===================================================================== Sorted By : Signal Multiplier: : 1.0000 Dilution: : 1.0000 Use Multiplier & Dilution Factor with ISTDs

Signal 1: FID1 A, Front Signal Peak RetTime Type Width Area Height Area # [min] [min] [pA*s] [pA] % ----|-------|----|-------|----------|----------|--------| 1 55.911 BB 0.0877 874.01947 158.17586 49.57828 2 56.320 BB 0.0881 888.88849 154.14984 50.42172 Totals :

1762.90796

312.32570

Supplementary Figure 154. GC spectrum for rac-11. Instrument 1 12/13/2016 2:18:44 PM

230

Page

1 of 2

Supplementary Figure 155. 1H NMR (300 MHz, CDCl3) spectrum for (S)-8.

231

10

2016-12-05 14:23:14.667 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz

7.260

8

6

0.99

3.599 3.577 3.556

4

zj-7-118

2.00

1.83

2

2.00

8.09

9.01

0

5.97

PPM

1.729 1.718 1.706 1.691 1.676 1.653 1.646 1.519 1.497 1.475 1.455 1.433 1.420 1.411 1.336 1.313 1.300 1.289 0.867 0.024

2.441 2.434

4.355 4.337 4.317

Supplementary Figure 156. 1H NMR (300 MHz, CDCl3) spectrum for (S)-11.

232

10

2016-12-07 00:04:03.078 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz

8

6

5.346 5.340 5.324 5.318 5.302 5.296 1.00

4

2.00

3.604 3.583 3.561

zj-7-120-1

0.95

2

2.99 1.99

8.08

8.98

0

6.00

2.442 2.435 1.788 1.766 2.074 1.746 1.739 1.716 1.513 1.497 1.475 1.455 1.437 1.412 1.343 1.321 1.308 0.876 0.031

7.260

PPM

Supplementary Figure 157. 13C NMR (75 MHz, CDCl3) spectrum for (S)-11.

233

200

169.911

2016-12-07 00:37:37.656 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 563 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz

150

zj-7-120-1

100

50

0

-5.331

34.442 32.631 28.826 25.921 25.572 24.800 20.939 18.310

81.228 77.423 77.000 76.568 73.378 63.718 63.111

PPM

Data File C:\CHEM32\1\DATA\SIG10190.D Sample Name: 7-120-1 ===================================================================== Acq. Operator : Acq. Instrument : Instrument 1 Location : Vial 1 Injection Date : 12/13/2016 11:32:29 AM Inj Volume : Manually Acq. Method : C:\CHEM32\1\METHODS\DEF_GC.M Last changed : 12/13/2016 11:32:28 AM (modified after loading) Analysis Method : C:\CHEM32\1\METHODS\DEF_GC.M Last changed : 12/13/2016 2:20:26 PM (modified after loading) Sample Info : dexcb

FID1 A, Front Signal (SIG10190.D) pA 900

800

700

600

500

56.324

400

300

200

100

0 0

10

20

30

40

min

50

===================================================================== Area Percent Report ===================================================================== Sorted By : Signal Multiplier: : 1.0000 Dilution: : 1.0000 Use Multiplier & Dilution Factor with ISTDs

Signal 1: FID1 A, Front Signal Peak RetTime Type Width Area Height Area # [min] [min] [pA*s] [pA] % ----|-------|----|-------|----------|----------|--------| 1 56.324 BB 0.0918 1594.40137 262.14978 1.000e2 Totals :

1594.40137

262.14978

Supplementary Figure 158. GC spectrum for (S)-11. Instrument 1 12/13/2016 2:20:29 PM

234

Page

1 of 2

Data File C:\CHEM32\1\DATA\SIG10188.D Sample Name: 7-111-rac ===================================================================== Acq. Operator : Acq. Instrument : Instrument 1 Location : Vial 1 Injection Date : 12/13/2016 9:09:27 AM Inj Volume : Manually Acq. Method : C:\CHEM32\1\METHODS\DEF_GC.M Last changed : 12/13/2016 9:09:26 AM (modified after loading) Analysis Method : C:\CHEM32\1\METHODS\DEF_GC.M Last changed : 12/13/2016 2:18:41 PM (modified after loading) Sample Info : dexcb

FID1 A, Front Signal (SIG10188.D) pA 900

800

700

600

500

400

55.911 56.320

300

200

100

0 0

10

20

30

40

min

50

===================================================================== Area Percent Report ===================================================================== Sorted By : Signal Multiplier: : 1.0000 Dilution: : 1.0000 Use Multiplier & Dilution Factor with ISTDs

Signal 1: FID1 A, Front Signal Peak RetTime Type Width Area Height Area # [min] [min] [pA*s] [pA] % ----|-------|----|-------|----------|----------|--------| 1 55.911 BB 0.0877 874.01947 158.17586 49.57828 2 56.320 BB 0.0881 888.88849 154.14984 50.42172 Totals :

1762.90796

312.32570

Supplementary Figure 159. GC spectrum for rac-11. Instrument 1 12/13/2016 2:18:44 PM

235

Page

1 of 2

236

10

Supplementary Figure 160. 1H NMR (300 MHz, CDCl3) spectrum for (S)-8.

7.260

8

2016-12-17 18:07:49.345 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz

6

0.99

3.599 3.577 3.556

4

zj-7-140

2.00

1.85

2

1.94

8.06

8.99

0

5.98

1.729 1.718 1.706 1.691 1.676 1.653 1.646 1.519 1.497 1.475 1.455 1.433 1.420 1.411 1.336 1.313 1.300 1.289 0.867 0.024

2.441 2.434

4.355 4.337 4.317

PPM

Supplementary Figure 161. 13C NMR (75 MHz, CDCl3) spectrum for (S)-8.

237

200

150

2016-12-17 17:28:50.125 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 177 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz

100

77.423 77.000 76.577 72.726

85.034

zj-7-140

50

0

-5.331

32.640 28.964 25.921 25.627 24.947 18.301

37.484

63.185 62.100

PPM

Supplementary Figure 162. 1H NMR (300 MHz, CDCl3) spectrum for (R)-9.

238

10

7.349

8

2016-12-13 13:31:33.656 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz

6

4

1.00

2.00

3.00

3.957 3.950 3.936 3.929 3.914 3.907 3.611 3.589 3.567 3.404 2.799 2.483 2.476

zj-7-129

0.99

0.97

2

2.01

8.09

0

1.754 1.732 1.713 1.691 1.669 1.576 1.553 1.530 1.508 1.480 1.465 1.443 1.390 1.372 1.362 1.352 1.340 1.317 0.000

PPM

Supplementary Figure 163. 13C NMR (75 MHz, CDCl3) spectrum for (R)-9.

239

200

150

2016-12-13 13:47:50.859 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 157 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz

100

zj-7-129

50

35.030 32.208 28.780 25.342 24.745

56.015

62.045

77.423 77.000 76.577 73.737 70.731

82.239

0

PPM

Supplementary Figure 164. 1H NMR (300 MHz, CDCl3) spectrum for (R)-10.

240

10

9.767 9.762 9.757

0.97

8

2016-12-15 09:23:14.357 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz

6

3.957 3.952 3.936 3.930 3.915 3.909 3.402

zj-7-135

4

1.00

3.01

3.00

2

4.06

4.15

0

2.484 2.478 2.470 2.451 2.446 2.426 2.421 1.757 1.746 1.734 1.719 1.713 1.703 1.698 1.678 1.654 1.629 1.605 1.535 1.515 1.503 1.488 1.480 1.476 1.467 1.459 1.437 1.410 1.386 1.362 1.339 1.334 1.316 0.000

7.332

-2

PPM

Supplementary Figure 165. 13C NMR (75 MHz, CDCl3) spectrum for (R)-10.

241

201.972

200

2016-12-15 11:03:25.127 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 149 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz

150

zj-7-135

100

50

24.119 21.206

28.081

34.525

43.045

55.758

81.862 77.423 77.000 76.568 73.388 70.170

0

PPM

Supplementary Figure 166. 1H NMR (300 MHz, CDCl3) spectrum for (R)-1c.

242

10

6.408 6.384 6.360

7.271

8

2016-12-15 20:24:03.593 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz

1.00

6

zj-7-137

4

3.961 3.954 3.940 3.933 3.918 3.911 3.416 1.00

2.99

0.94

2

2.02 2.00

6.14

0

2.452 2.445 2.137 2.114 2.089 2.065 1.761 1.751 1.739 1.723 1.708 1.686 1.525 1.488 1.474 1.425 1.399 1.378 1.367 1.345 1.314 -0.000

PPM

Supplementary Figure 167. 13C NMR (75 MHz, CDCl3) spectrum for (R)-1c.

243

200

2016-12-17 11:03:17.562 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 606 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz

150

zj-7-137

100

50

28.642 27.612 24.763

35.288 32.833

56.456

82.579 77.423 77.000 76.577 73.792 70.924

88.618

138.668

0

PPM

244

10

Supplementary Figure 168. 1H NMR (300 MHz, CDCl3) spectrum for (S)-9.

7.358

8

2016-12-19 11:02:22.781 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz

6

4

1.00

2.00

2.98

3.958 3.952 3.937 3.930 3.914 3.908 3.607 3.585 3.563 3.405 2.983 2.491 2.484

zj-7-142

0.98

0.93

2

2.01

8.02

0

1.798 1.771 1.739 1.712 1.701 1.691 1.668 1.646 1.598 1.574 1.551 1.528 1.506 1.479 1.464 1.435 1.387 1.360 1.350 1.338 1.325 0.000

PPM

Supplementary Figure 169. 13C NMR (75 MHz, CDCl3) spectrum for (S)-9.

245

200

150

2016-12-19 11:09:49.140 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 88 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz

100

zj-7-142

50

35.113 32.309 28.844 25.406 24.818

56.144

62.256

77.432 77.000 76.577 73.746 70.823

82.340

0

PPM

Supplementary Figure 170. 1H NMR (300 MHz, CDCl3) spectrum for (S)-10.

246

9.768 9.762 9.756

10

0.97

2016-12-20 20:18:20.562 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz

8

6

3.959 3.952 3.938 3.931 3.916 3.909 3.402

zj-7-143

4

1.00

3.00

3.00

2

4.02

4.11

0

2.487 2.480 2.476 2.451 2.446 2.427 2.421 1.758 1.735 1.725 1.714 1.703 1.678 1.654 1.628 1.604 1.540 1.534 1.503 1.487 1.480 1.457 1.436 1.409 1.394 1.373 1.362 1.333 1.309 -0.000

7.349

PPM

Supplementary Figure 171. 13C NMR (75 MHz, CDCl3) spectrum for (S)-10.

247

202.340

200

2016-12-20 21:00:28.234 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 667 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz

150

100

zj-7-143

50

24.496 21.583

28.458

34.892

43.404

56.107

82.230 77.423 77.000 76.577 73.673 70.557

0

PPM

Supplementary Figure 172. 1H NMR (300 MHz, CDCl3) spectrum for (S)-1c.

248

10

7.283

8

2016-12-20 20:00:14.265 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz

6

0.98

4

1.00

3.957 3.951 3.936 3.929 3.914 3.908 3.410

zj-7-146

3.00

0.94

2

2.00

2.01

6.08

0

2.455 2.448 2.136 2.112 2.088 2.063 1.757 1.729 1.703 1.682 1.518 1.496 1.485 1.472 1.448 1.421 1.398 1.387 1.366 1.343 1.329 1.313 1.299 0.000

6.407 6.383 6.358

PPM

Supplementary Figure 173. 13C NMR (75 MHz, CDCl3) spectrum for (S)-1c.

249

200

2016-12-21 00:04:07.333 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 238 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz

150

100

zj-7-146

50

28.596 27.566 24.708

35.232 32.787

56.392

82.524 77.423 77.000 76.577 73.774 70.842

88.591

138.604

0

PPM

250

10

Supplementary Figure 174. 1H NMR (300 MHz, CDCl3) spectrum for (Ra,R)-4ck.

7.304

8

2016-12-20 14:25:48.062 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz

0.99

6

5.316 5.295 5.275 5.255 5.023 5.013 5.007 4.997 4.991 4.980 4.970 1.00 1.00

zj-7-138

4

3.682 3.615 3.593 3.569 3.546 3.295 1.01

3.01 3.00

2.01

2.04

2

2.03

8.43

2.465 2.438 2.415 2.365 2.340 2.324 2.134 2.110 2.087 2.062 1.610 1.569 1.541 1.493 1.464 1.442 1.420 1.366 -0.000

6.413 6.389 6.365

0PPM

Supplementary Figure 175. 13C NMR (75 MHz, CDCl3) spectrum for (Ra,R)-4ck.

251

173.119

200

2016-12-20 14:52:19.000 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 411 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz

150

zj-7-138

100

51.484

50

35.545 33.045 32.797 28.798 27.612 25.057 23.596

55.951

80.190 77.423 77.000 76.577

93.297 90.264 88.471

138.649

204.160

0PPM

zj-7-138-if-100-1-1-214 实验时间:2017-03-02,12:21:23 谱图文件:D:\zhuguangjiong\zj\20170302\zj-7-138-if-100-1-1214.org

报告时间:2017-03-02,18:32:20

实验内容简介:

色谱图(zj-7-138-if-100-1-1-214.org) 3,400 3,200 3,000 2,800 2,600

2,000 1,800

25.853

电压(mv)

2,400 2,200

1,600 1,400 1,200 1,000

0 0

34.908

400 200 2

4

6

50.862

800 600

8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50 52 54 56 58

时间(min)

峰号 1 2 3

峰名

保留时间

分析结果表 峰高

25.853 34.908 50.862

总计

峰面积

含量

1479945.500 950.974 1857.505

51123048.000 43397.344 191656.438

99.5423 0.0845 0.3732

1482753.979

51358101.781

100.0000

Supplementary Figure 176. HPLC spectrum for (Ra,R)-4ck. 252

zj-7-114-if-100-1-1-214 实验时间:2017-03-02,11:12:11 谱图文件:D:\zhuguangjiong\zj\20170302\zj-7-114-if-100-1-1214.org

报告时间:2017-03-02,18:33:43

实验内容简介:

色谱图(zj-7-114-if-100-1-1-214.org)

1,500 1,400 1,300 1,200 1,100 1,000

500 400 300 200

49.057

600

33.790

700

27.790

800

25.190

电压(mv)

900

100 0 0

2 4

6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50 52 54 56 58 60

时间(min)

峰号 1 2 3 4

峰名

保留时间

分析结果表 峰高

25.190 27.790 33.790 49.057

总计

峰面积

含量

568287.688 492501.188 333279.406 173895.328

19152964.000 19221222.000 16885436.000 16834350.000

26.5667 26.6613 23.4214 23.3506

1567963.609

72093972.000

100.0000

Supplementary Figure 177. HPLC spectrum for rac-4ck. 253

Supplementary Figure 178. 1H NMR (300 MHz, CDCl3) spectrum for (Ra,R)-5k.

254

9.681

10

0.93

2016-12-22 22:35:00.906 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz

8

0.98

6

0.99

5.333 5.313 5.293 5.272 5.059 5.038 5.021 5.001 4.990 0.99

zj-7-144

3.635 3.615 3.590 3.565 3.307

4

1.00

3.00

2.02

2.01

2

2.03

9.00

0PPM

2.511 2.487 2.465 2.376 2.355 2.323 2.310 2.131 2.107 2.083 2.059 1.641 1.610 1.579 1.551 1.524 1.503 1.481 1.456 1.414 1.360 1.294 1.253 -0.000

6.412 6.388 6.363

7.278

Supplementary Figure 179. 13C NMR (75 MHz, CDCl3) spectrum for (Ra,R)-5k.

255

200

178.893

2016-12-22 23:33:21.116 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 507 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz

150

zj-7-144

100

50

35.546 33.129 32.917 28.900 27.715 25.169 23.385

56.016

80.393 77.488 77.066 76.643

93.501 90.237 88.583

138.770

204.345

PPM

256

Supplementary Figure 180. 1H NMR (300 MHz, CDCl3) spectrum for xestospongiene F ((5S,1’E,3’R)-6k). 10 8

2017-02-20 18:13:05.000 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz

7.356

6.413 6.388 6.364

1.00

5.764 5.745 5.712 5.693 5.684 5.663 5.632 5.611 5.552 5.515 5.486 5.335 5.316 5.285 5.259 5.015 4.992 4.973 4.949 3.613 3.592 3.572 3.551 3.265 2.586 2.565 2.536 2.517 2.480 2.462 2.440 2.418 2.394 2.125 2.102 2.077 2.053 2.030 2.014 1.988 1.957 1.574 1.520 1.481 1.447 1.425 1.405 1.324 0.000

6 0.03

2.02

0.02 1.00

zj-7-188

4 1.00 3.00 3.09

2

3.08 8.59

0 PPM

257

Supplementary Figure 181. 1H NMR (300 MHz, CDCl3) extended spectrum for xestospongiene F. 6.5 1.00

6.413 6.388 6.364

6.0 2.02

5.764 5.745 5.712 5.693 5.684 5.663 5.632 5.611 5.552 5.515 5.486

5.5

0.03 0.02

5.335 5.316 5.285 5.259

5.0

5.015 4.992 4.973 4.949

1.00

zj-7-188

PPM

Supplementary Figure 182. 13C NMR (75 MHz, CDCl3) spectrum for xestospongiene F ((5S,1’E,3’R)-6k).

258

176.566

200

2017-02-20 18:23:50.750 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 161 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz

150

zj-7-188

100

50

34.754 32.576 28.587 28.458 28.201 27.337 24.551

56.135

80.759 79.712 77.423 77.000 76.577

88.232

129.439

134.090

138.512

0 PPM

Supplementary Figure 183. Quantitative 13C NMR (75 MHz, CDCl3) spectrum for xestospongiene F.

259

200

176.610

2017-02-21 08:53:50.578 USER: nmr SOLVENT: CDCl3 Experiment = zgig30 Pulse length = 9.500 usec Relaxation delay = 60.000 sec NA = 605 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz

150

138.501 135.578 134.080 129.447 1.00 0.02

100

0.03

80.750 79.730 77.423 77.000 76.577

88.223

zj-7-188-Q

50

34.746 32.568 28.578 28.450 28.220 27.328 24.553

56.135

0

PPM

PPM 134

1.00

133

132

131

130

129.447 0.02

135

134.080

136

135.578

Supplementary Figure 184. Quantitative 13C NMR (75 MHz, CDCl3) extended spectrum for xestospongiene F. 260

Data File C:\CHEM32\1\DATA\2014-44651.D Sample Name: zj-7-188 ===================================================================== Acq. Operator : 系统 Sample Operator : 系统 Acq. Instrument : SFC Location : Vial 46 Injection Date : 10/03/2017 15:47:57 Inj Volume : 5.000 µl Acq. Method : C:\CHEM32\1\METHODS\DEF_LC-TEST-2016.M Last changed : 10/03/2017 15:12:15 by 系统 (modified after loading) Analysis Method : C:\CHEM32\1\METHODS\DEF_LC-TEST-2016.M Last changed : 13/03/2017 09:52:48 by 系统 (modified after loading) Additional Info : Peak(s) manually integrated DAD1 A, Sig=214,16 Ref=360,100 (2014-44651.D) mAU

800

15.775

600

400

200

0 0

5

10

15

20

min

===================================================================== Area Percent Report ===================================================================== Sorted By Multiplier Dilution Do not use Multiplier

: Signal : 1.0000 : 1.0000 & Dilution Factor with ISTDs

Signal 1: DAD1 A, Sig=214,16 Ref=360,100 Peak RetTime Type Width Area Height Area # [min] [min] [mAU*s] [mAU] % ----|-------|----|-------|----------|----------|--------| 1 15.775 VV 0.5656 1.49946e4 325.08957 100.0000 Totals :

1.49946e4

325.08957

===================================================================== *** End of Report ***

Supplementary Figure 185. SFC spectrum for xestospongiene F.

SFC 13/03/2017 09:52:52 系统

261

Page

1 of 1

Data File C:\CHEM32\1\DATA\2014-44652.D Sample Name: zj-7-158-rac-ad-h-sfc-97-3-1.3-214 ===================================================================== Acq. Operator : 系统 Sample Operator : 系统 Acq. Instrument : SFC Location : Vial 41 Injection Date : 10/03/2017 16:22:52 Inj Volume : 5.000 µl Acq. Method : C:\CHEM32\1\METHODS\DEF_LC-TEST-2016.M Last changed : 10/03/2017 16:20:37 by 系统 (modified after loading) Analysis Method : C:\CHEM32\1\METHODS\DEF_LC-TEST-2016.M Last changed : 13/03/2017 09:50:59 by 系统 (modified after loading) Additional Info : Peak(s) manually integrated DAD1 A, Sig=214,16 Ref=360,100 (2014-44652.D) mAU

400

100

21.277

16.324

14.450

200

17.388

300

0

0

5

10

15

20

min

===================================================================== Area Percent Report ===================================================================== Sorted By Multiplier Dilution Do not use Multiplier

: Signal : 1.0000 : 1.0000 & Dilution Factor with ISTDs

Signal 1: DAD1 A, Sig=214,16 Ref=360,100 Peak RetTime Type Width Area Height Area # [min] [min] [mAU*s] [mAU] % ----|-------|----|-------|----------|----------|--------| 1 14.450 MM R 0.3913 3141.53149 127.69143 24.0477 2 16.324 MF R 0.4819 3396.79004 113.02892 26.0016 3 17.388 FM R 0.5002 3149.34937 98.45376 24.1075 4 21.277 MM R 0.6807 3376.07983 78.39977 25.8431 Totals :

1.30638e4

417.57388

===================================================================== *** End of Report ***

Supplementary Figure 186. SFC spectrum for rac-xestospongiene.

SFC 13/03/2017 09:51:52 系统

262

Page

1 of 1

263

10

Supplementary Figure 187. 1H NMR (300 MHz, CDCl3) spectrum for (Sa,R)-4ck.

7.302

8

2016-12-20 13:43:17.578 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz

0.99

6

1.00 1.00

4

1.04

3.01

5.265 5.245 5.224 5.204 5.026 5.016 5.006 4.995 4.989 4.979 4.968 4.958 3.682 3.612 3.592 3.568 3.545 3.322

zj-7-139

2.99

2.02

2.02

2

2.01

8.58

0

2.497 2.469 2.446 2.393 2.384 2.372 2.362 2.350 2.340 2.311 2.125 2.101 2.077 2.053 1.647 1.627 1.604 1.584 1.564 1.533 1.506 1.484 1.447 1.428 1.405 1.382 1.344 1.333 0.000

6.406 6.382 6.357

PPM

Supplementary Figure 188. 13C NMR (75 MHz, CDCl3) spectrum for (Sa,R)-4ck.

264

173.128

204.095

200

2016-12-20 14:07:26.343 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 389 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz

150

zj-7-139

100

51.474

50

35.600 33.146 32.787 28.761 27.603 24.974 23.807

56.006

80.226 77.432 77.000 76.577

93.306 90.227 88.471

138.668

0 PPM

电 (mv )压

zj-7-139-if-100-1-1-214 实验时间:2016-12-29,16:30:56 谱图文件:F:\zhuguangjiong\zj\20161229\zj-7-139-if-100-1-1214.org

报告时间:2016-12-29,17:41:44

实验内容简介:

色谱图(zj-7-139-if-100-1-1-214.org)

1,500 1,400 1,300 1,200 1,100 1,000

800 36.618

电压(mv)

900

700 600 500 400

100 0 0

2

4

6

25.635

18.925

200

21.142

300

8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50 52 54

时间(min)

峰号 1 2 3 4

峰名

保留时间

分析结果表 峰高

18.925 21.142 25.635 36.618

总计

峰面积

含量

7426.935 1433.861 2646.305 568388.500

442951.219 62236.391 77021.773 69295464.000

0.6339 0.0891 0.1102 99.1668

579895.601

69877673.383

100.0000

Supplementary Figure 189. HPLC spectrum for (Sa,R)-4ck. 265

电 (mv )压

zj-7-114-if-100-1-1-214 实验时间:2016-12-29,13:10:36 谱图文件:F:\zhuguangjiong\zj\20161229\zj-7-114-if-100-1-1214.org

报告时间:2016-12-29,17:38:32

实验内容简介:

色谱图(zj-7-114-if-100-1-1-214.org) 2,400 2,200 2,000

1,400 1,200

26.177

电压(mv)

1,600

20.037 21.892

1,800

1,000

37.362

800 600 400 200

0 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50 52 54 56 58 60

时间(min)

峰号 1 2 3 4

峰名

保留时间

分析结果表 峰高

20.037 21.892 26.177 37.362

总计

峰面积

含量

1370312.625 1249851.375 792350.000 380083.000

33698112.000 34018172.000 31096976.000 30855660.000

25.9878 26.2346 23.9818 23.7957

3792597.000

129668920.000

100.0000

Supplementary Figure 190. HPLC spectrum for rac-4ck. 266

267

Supplementary Figure 191. 1H NMR (300 MHz, CDCl3) spectrum for (Sa,R)-5k. 10 0.87

8

2016-12-22 22:43:33.593 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz

9.718

6.404 6.380 7.277 6.357

0.98

5.281 5.262 5.242 5.221 5.055 5.045 5.034 5.024 5.018 5.007 4.997 4.987 3.633 3.612 3.589 3.564 3.331 2.542 2.518 2.495 2.400 2.390 2.379 2.369 2.347 2.324 2.124 2.100 2.076 2.051 1.667 1.659 1.635 1.606 1.576 1.560 1.541 1.513 1.491 1.471 1.447 1.425 1.403 1.379 1.343 1.332 1.318 1.301 1.253 0.000

6 1.00

1.00

zj-7-145

4 1.02 3.01 2.01

1.97

2

2.01 8.56

0 PPM

Supplementary Figure 192. 13C NMR (75 MHz, CDCl3) spectrum for (Sa,R)-5k.

268

178.827

204.169

200

2016-12-23 23:14:09.655 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 599 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz

150

zj-7-145

100

50

35.600 33.164 32.843 28.807 27.658 25.029 23.550

56.061

80.337 77.432 77.000 76.577

93.527 90.153 88.536

138.723

0 PPM

269

10

Supplementary Figure 193. 1H NMR (300 MHz, CDCl3) spectrum for xestospongiene G.

6.406 6.382 6.358

7.298

8

2017-03-19 23:48:03.453 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz

1.00

6

5.758 5.739 5.706 5.681 5.661 5.630 5.608 5.014 4.991 4.972 4.949 2.00 1.00

3.602 3.581 3.561 3.539 3.274

4

zj-8-012

1.00

3.00 3.00

2

3.01

8.25

0

2.594 2.570 2.541 2.487 2.466 2.424 2.401 2.378 2.125 2.102 2.077 2.053 2.018 2.002 1.976 1.945 1.598 1.566 1.549 1.528 1.503 1.484 1.448 1.428 1.402 1.340 1.323 1.254 -0.000

PPM

Supplementary Figure 194. 13C NMR (75 MHz, CDCl3) spectrum for xestospongiene G.

270

176.474

200

2017-03-22 13:21:08.143 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 412 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz

150

zj-8-012

100

50

34.718 32.521 28.522 28.403 28.118 27.291 24.515

56.061

80.741 79.564 77.423 77.000 76.568

88.177

129.651

133.879

138.475

0

PPM

SAMPLE Sample Name: ZJ8012 ADH912200040 Sample Type: Vial: 1:A,5 Injection: 1 Injection Volume: 3.00 ul Run Time: 30.0 Minutes Sample Set Name:20170322

INF O R MA T IO N Acquired By: Date Acquired: Acq. Method Set: Date Processed: Processing Method: Channel Name: Proc. Chnl. Descr:

System 2017/3/22 18:02:58 CST chiral_isocratic 2017/3/23 14:19:41 CST 1 PDA Ch1 214 [email protected] nm PDA Ch1 214 [email protected] nm

16.213

0.24 0.22 0.20 0.18 0.16

AU

0.14 0.12 0.10 0.08 0.06

11.263

0.04 0.02 0.00 0.00

2.00

4.00

6.00

8.00

10.00

12.00

14.00 16.00 Minutes

Peak Results RT

Height

% Area

29947

2316

0.39

2 16.213 7743535

229889

99.61

1

11.263

Area

Supplementary Figure 195. SFC spectrum for xestospongiene G. 271

18.00

20.00

22.00

24.00

26.00

28.00

30.00

SAMPLE

0.60

Acquired By: Date Acquired: Acq. Method Set: Date Processed: Processing Method: Channel Name: Proc. Chnl. Descr:

System 2017/3/22 14:45:20 CST chiral_isocratic 2017/3/23 14:07:00 CST 1 PDA Ch1 214 [email protected] nm PDA Ch1 214 [email protected] nm

10.552

9.078

Sample Name: ZJ7-158 adh912214200040 Sample Type: Vial: 1:A,1 Injection: 1 Injection Volume: 5.00 ul Run Time: 30.0 Minutes Sample Set Name:20170213

INF O R MA T IO N

14.833

AU

0.40

0.30

18.726

0.50

0.20

0.10

0.00 0.00

2.00

4.00

6.00

8.00

10.00

12.00

14.00 16.00 Minutes

Peak Results RT 1

Area

Height

% Area

635306

24.26

11177453 563713

26.15

9.078 10369086

2 10.552

3 14.833 10145220 4 18.726

298583

23.73

11052066 239962

25.86

Supplementary Figure 196. SFC spectrum for rac-xestospongiene. 272

18.00

20.00

22.00

24.00

26.00

28.00

30.00

273

10

Supplementary Figure 197. 1H NMR (300 MHz, CDCl3) spectrum for (Ra,S)-4ck.

6.406 6.381 6.357

8

0.99

2016-12-24 20:30:19.078 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz

6

1.00 1.00

zj-7-148

4

1.01

2.99

0.01

2.99 2.00 2.00

2

2.00

8.16

0

5.266 5.245 5.225 5.204 5.027 5.016 5.006 4.996 4.990 4.979 4.968 4.959 3.682 3.615 3.592 3.568 3.546 3.323 3.296 2.497 2.469 2.446 2.394 2.384 2.373 2.362 2.352 2.340 2.329 2.125 2.102 2.077 2.053 1.617 1.604 1.585 1.534 1.514 1.484 1.460 1.448 1.428 1.405 1.382 1.345 1.320 1.302 0.000

7.300

PPM

Supplementary Figure 198. 13C NMR (75 MHz, CDCl3) spectrum for (Ra,S)-4ck.

274

173.146

200

2016-12-24 20:56:31.031 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 428 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz

150

zj-7-148

100

51.502

50

35.609 33.146 32.787 28.761 27.612 24.984 23.807

56.015

80.236 77.432 77.000 76.577

93.306 90.236 88.471

138.677

204.095

0

PPM

电 (mv )压

zj-7-148-if-100-1-1-214 实验时间:2016-12-29,14:26:02 谱图文件:F:\zhuguangjiong\zj\20161229\zj-7-148-if-100-1-1214.org

报告时间:2016-12-29,17:43:32

实验内容简介:

色谱图(zj-7-148-if-100-1-1-214.org)

1,500 1,400 1,300 1,200 1,100 1,000

800

25.655

电压(mv)

900

700 600 500 400

100 0 0

2

4

6

37.877

19.177

200

21.437

300

8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50 52 54

时间(min)

峰号 1 2 3 4

峰名

保留时间

分析结果表 峰高

19.177 21.437 25.655 37.877

总计

峰面积

含量

2891.311 3269.852 611125.375 730.933

167002.906 175523.078 34820224.000 30796.018

0.4745 0.4987 98.9392 0.0875

618017.471

35193546.002

100.0000

Supplementary Figure 199. HPLC spectrum for (Ra,S)-4ck. 275

电 (mv )压

zj-7-114-if-100-1-1-214 实验时间:2016-12-29,13:10:36 谱图文件:F:\zhuguangjiong\zj\20161229\zj-7-114-if-100-1-1214.org

报告时间:2016-12-29,17:38:32

实验内容简介:

色谱图(zj-7-114-if-100-1-1-214.org) 2,400 2,200 2,000

1,400 1,200

26.177

电压(mv)

1,600

20.037 21.892

1,800

1,000

37.362

800 600 400 200

0 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50 52 54 56 58 60

时间(min)

峰号 1 2 3 4

峰名

保留时间

分析结果表 峰高

20.037 21.892 26.177 37.362

总计

峰面积

含量

1370312.625 1249851.375 792350.000 380083.000

33698112.000 34018172.000 31096976.000 30855660.000

25.9878 26.2346 23.9818 23.7957

3792597.000

129668920.000

100.0000

Supplementary Figure 200. HPLC spectrum for rac-4ck. 276

277

Supplementary Figure 201. 1H NMR (300 MHz, CDCl3) spectrum for (Ra,S)-5k. 10.730 0.95

10 8

2016-12-26 21:06:23.315 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz

6.404 6.379 6.355

0.98

6 1.00

1.00

zj-7-151

4 1.00 3.00

2

2.00 2.00 1.99 8.36

0 -2

5.280 7.291 5.259 5.238 5.218 5.053 5.043 5.032 5.026 5.022 5.016 5.006 4.995 4.985 3.637 3.615 3.594 3.571 3.331 2.539 2.512 2.488 2.396 2.386 2.375 2.365 2.353 2.326 2.319 2.122 2.099 2.075 2.050 1.669 1.648 1.629 1.617 1.607 1.576 1.559 1.532 1.512 1.491 1.470 1.446 1.424 1.401 1.379 1.350 1.342 1.318 1.299 1.280 0.000

PPM

Supplementary Figure 202. 13C NMR (75 MHz, CDCl3) spectrum for (Ra,S)-5k.

278

200

178.781

2017-01-02 12:09:40.377 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 574 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz

150

zj-7-151

100

50

35.508 33.127 32.787 28.743 27.603 24.965 23.504

55.969

80.300 77.423 77.000 76.577

93.444 90.126 88.499

138.659

204.123

0 PPM

279

10

Supplementary Figure 203. 1H NMR (300 MHz, CDCl3) spectrum for xestospongiene H.

7.384

8

2017-03-20 23:42:22.359 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz

1.00

6

1.00

5.763 5.744 5.711 5.691 5.673 5.652 5.622 5.600 5.016 4.993 4.971 4.948 2.00

4

3.605 3.584 3.563 3.541 3.263

zj-8-013

1.00

3.00

3.02

2

3.00

8.32

0

2.586 2.560 2.531 2.497 2.472 2.453 2.432 2.409 2.384 2.124 2.100 2.076 2.051 2.018 1.987 1.946 1.600 1.585 1.558 1.537 1.520 1.499 1.479 1.449 1.426 1.405 1.335 1.323 0.000

6.414 6.391 6.366

PPM

Supplementary Figure 204. 13C NMR (75 MHz, CDCl3) spectrum for xestospongiene H.

280

200

176.437

2017-03-21 00:06:53.156 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 376 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz

150

100

zj-8-013

50

34.681 32.484 28.486 28.357 28.081 27.254 24.469

56.015

80.695 79.519 77.423 77.000 76.568

88.131

129.632

133.824

138.447

0 PPM

SAMPLE Sample Name: ZJ8013 ADH912200040 Sample Type: Vial: 1:A,6 Injection: 1 Injection Volume: 3.00 ul Run Time: 30.0 Minutes Sample Set Name:20170322

INF O R MA T IO N Acquired By: Date Acquired: Acq. Method Set: Date Processed: Processing Method: Channel Name: Proc. Chnl. Descr:

System 2017/3/22 18:33:53 CST chiral_isocratic 2017/3/23 14:20:07 CST 1 PDA Ch1 214 [email protected] nm PDA Ch1 214 [email protected] nm

9.389

0.70

0.60

0.50

AU

0.40

0.30

0.20

0.00 0.00

2.00

4.00

6.00

8.00

10.00

12.00

20.824

11.900

0.10

14.00 16.00 Minutes

Peak Results RT

Area

Height

% Area

11206012 680745

99.48

1

9.389

2

11.900

42814

2644

0.38

3 20.824

15359

822

0.14

Supplementary Figure 205. SFC spectrum for xestospongiene H. 281

18.00

20.00

22.00

24.00

26.00

28.00

30.00

SAMPLE

0.60

Acquired By: Date Acquired: Acq. Method Set: Date Processed: Processing Method: Channel Name: Proc. Chnl. Descr:

System 2017/3/22 14:45:20 CST chiral_isocratic 2017/3/23 14:07:00 CST 1 PDA Ch1 214 [email protected] nm PDA Ch1 214 [email protected] nm

10.552

9.078

Sample Name: ZJ7-158 adh912214200040 Sample Type: Vial: 1:A,1 Injection: 1 Injection Volume: 5.00 ul Run Time: 30.0 Minutes Sample Set Name:20170213

INF O R MA T IO N

14.833

AU

0.40

0.30

18.726

0.50

0.20

0.10

0.00 0.00

2.00

4.00

6.00

8.00

10.00

12.00

14.00 16.00 Minutes

Peak Results RT 1

Area

Height

% Area

635306

24.26

11177453 563713

26.15

9.078 10369086

2 10.552

3 14.833 10145220 4 18.726

298583

23.73

11052066 239962

25.86

Supplementary Figure 206. SFC spectrum for rac-xestospongiene. 282

18.00

20.00

22.00

24.00

26.00

28.00

30.00

283

10

Supplementary Figure 207. 1H NMR (300 MHz, CDCl3) spectrum for (Sa,S)-4ck.

8

2016-12-27 19:18:41.265 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz

7.305

6.413 6.389 6.365

1.00

6 1.00 1.00

zj-7-150

4 2.97

0.03

1.01

3.00

2

2.02 2.01 2.00 8.25

0

5.316 5.295 5.274 5.254 5.028 5.018 5.007 4.990 4.980 4.970 4.960 3.682 3.615 3.593 3.569 3.546 3.322 3.295 2.465 2.458 2.443 2.437 2.412 2.369 2.356 2.346 2.336 2.324 2.314 2.303 2.296 2.286 2.134 2.110 2.086 2.061 1.639 1.620 1.608 1.598 1.585 1.541 1.521 1.492 1.460 1.441 1.419 1.396 1.382 1.364 1.350 1.330 -0.000

-2 PPM

Supplementary Figure 208. 13C NMR (75 MHz, CDCl3) spectrum for (Sa,S)-4ck.

284

173.119

200

2016-12-27 19:27:13.578 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 131 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz

150

zj-7-150

100

51.484

50

35.536 33.026 32.787 28.789 27.603 25.048 23.577

55.942

80.190 77.423 77.000 76.577

93.279 90.255 88.462

138.650

204.141

0

PPM

电 (mv )压

zj-7-150-if-3-100-1-1-214 实验时间:2017-01-13,18:09:09 报告时间:2017-01-13,19:51:03 谱图文件:F:\zhuguangjiong\zj\20170113\zj-7-150-if-3-100-1-1214.org 实验内容简介:

色谱图(zj-7-150-if-3-100-1-1-214.org)

500 450 400 350

14.788

电压(mv)

300 250 200 150

0 2

3 4 5

6

25.448

13.458

50

0 1

17.810

100

7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30

时间(min)

峰号 1 2 3 4

峰名

保留时间

分析结果表 峰高

13.458 14.788 17.810 25.448

总计

峰面积

含量

103.315 204454.266 476.592 177.939

1663.211 3509839.000 9957.236 5422.999

0.0472 99.5168 0.2823 0.1538

205212.112

3526882.446

100.0000

Supplementary Figure 209. HPLC spectrum for (Sa,S)-4ck. 285

电 (mv )压

zj-7-114-if-3-100-1-1-214 实验时间:2017-01-13,19:04:56 报告时间:2017-01-13,19:48:04 谱图文件:F:\zhuguangjiong\zj\20170113\zj-7-114-if-3-100-1-1214.org

24.965

17.665

色谱图(zj-7-114-if-3-100-1-1-214.org)

14.765

1,000 950 900 850 800 750 700 650 600 550 500 450 400 350 300 250 200 150 100 50 0

13.515

电压(mv)

实验内容简介:

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30

时间(min)

峰号 1 2 3 4

峰名

保留时间

分析结果表 峰高

13.515 14.765 17.665 24.965

总计

峰面积

含量

415700.125 363298.375 253848.797 144203.688

6377944.000 6413361.000 5528617.000 5590452.500

26.6744 26.8225 23.1223 23.3809

1177050.984

23910374.500

100.0000

Supplementary Figure 210. HPLC spectrum for rac-4ck. 286

Supplementary Figure 211. 1H NMR (300 MHz, CDCl3) spectrum for (Sa,S)-5k.

287

10.123

10

0.92

2017-01-01 15:32:18.046 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz

8

0.98

6

5.332 5.311 5.291 5.271 5.048 5.037 5.027 5.021 5.011 5.000 1.00 1.00

4

3.636 3.614 3.589 3.566 3.331 3.306

zj-7-156

0.03

1.00

2.95

2.01

2.01

2

2.01

8.26

0

PPM

2.513 2.486 2.463 2.376 2.366 2.354 2.345 2.332 2.323 2.131 2.107 2.083 2.059 1.631 1.620 1.601 1.551 1.525 1.503 1.481 1.457 1.435 1.414 1.394 1.379 1.360 -0.000

7.278 6.411 6.387 6.363

Supplementary Figure 212. 13C NMR (75 MHz, CDCl3) spectrum for (Sa,S)-5k.

288

178.873

204.279

200

2017-01-01 16:11:52.703 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 660 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz

150

zj-7-156

100

50

35.517 33.081 32.861 28.853 27.658 25.112 23.338

55.969

80.327 77.423 77.000 76.577

93.472 90.163 88.527

138.714

0

PPM

289

10

Supplementary Figure 213. 1H NMR (300 MHz, CDCl3) spectrum for xestospongiene E ((5R,1’E,3’S)-6k).

7.352

8

2017-02-21 15:25:33.236 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz

1.00

6

0.01

2.00 0.01

0.99

zj-7-189

4

1.00

3.00

3.07

2

3.09

8.53

5.763 5.744 5.712 5.693 5.684 5.663 5.632 5.611 5.551 5.519 5.489 5.335 5.311 5.286 5.262 5.015 4.993 4.972 4.949 3.612 3.592 3.572 3.551 3.265 2.590 2.565 2.536 2.504 2.461 2.440 2.394 2.125 2.102 2.078 2.056 2.030 1.988 1.957 1.559 1.511 1.481 1.447 1.426 1.405 1.327 0.000

6.412 6.388 6.364

0

PPM

290

Supplementary Figure 214. 1H NMR (300 MHz, CDCl3) extended spectrum for xestospongiene E. 6.5 1.00

6.412 6.388 6.364

6.0 2.00

5.763 5.744 5.712 5.693 5.684 5.663 5.632 5.611 5.551 5.519 5.489

5.5

0.01 0.01

5.335 5.311 5.286 5.262

5.0

5.015 4.993 4.972 4.949

0.99

zj-7-189

PPM

291

200

Supplementary Figure 215. 13C NMR (75 MHz, CDCl3) spectrum for xestospongiene E ((5R,1’E,3’S)-6k).

176.566

150

2017-02-21 19:08:33.231 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 971 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz

88.269

100

zj-7-189

50

34.791 32.604 28.614 28.486 28.228 27.364 24.579

56.171

80.787 79.730 77.432 77.000 76.577

129.458

134.127

138.530

0 PPM

Supplementary Figure 216. Quantitative 13C NMR (75 MHz, CDCl3) spectrum for xestospongiene E.

292

200

176.794

2017-03-09 09:05:55.921 USER: nmr SOLVENT: CDCl3 Experiment = zgig30 Pulse length = 9.500 usec Relaxation delay = 60.000 sec NA = 1930 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz

150

134.374 129.999 129.530 1.00 0.02

88.453

100

zj-7-189-Q

50

34.939 32.742 28.772 28.643 28.404 27.521 24.755

56.356

80.962 79.932 77.432 77.000 76.577

138.630

0

PPM

PPM 128 129 1.00

129.999

132

131

130

0.02

129.530

Supplementary Figure 217. Quantitative 13C NMR (75 MHz, CDCl3) extended spectrum for xestospongiene E. 293

SAMPLE Sample Name: ZJ7-189 ADH912200040 Sample Type: Vial: 1:A,3 Injection: 1 Injection Volume: 3.00 ul Run Time: 30.0 Minutes Sample Set Name:20170322

INF O R MA T IO N Acquired By: Date Acquired: Acq. Method Set: Date Processed: Processing Method: Channel Name: Proc. Chnl. Descr:

System 2017/3/22 16:53:38 CST chiral_isocratic 2017/3/23 14:18:28 CST 1 PDA Ch1 214 [email protected] nm PDA Ch1 214 [email protected] nm

20.954

0.30

0.25

AU

0.20

0.15

0.10

0.00

2.00

4.00

6.00

8.00

10.00

12.00

17.331

0.00

11.643

9.915

0.05

14.00 16.00 Minutes

Peak Results RT

Area

Height

% Area

1

9.915

47327

3602

0.26

2

11.643

24645

1837

0.14

3 17.331

10850

486

0.06

4 20.954 17914997

315459

99.54

Supplementary Figure 218. SFC spectrum for xestospongiene E. 294

18.00

20.00

22.00

24.00

26.00

28.00

30.00

SAMPLE

0.60

Acquired By: Date Acquired: Acq. Method Set: Date Processed: Processing Method: Channel Name: Proc. Chnl. Descr:

System 2017/3/22 14:45:20 CST chiral_isocratic 2017/3/23 14:07:00 CST 1 PDA Ch1 214 [email protected] nm PDA Ch1 214 [email protected] nm

10.552

9.078

Sample Name: ZJ7-158 adh912214200040 Sample Type: Vial: 1:A,1 Injection: 1 Injection Volume: 5.00 ul Run Time: 30.0 Minutes Sample Set Name:20170213

INF O R MA T IO N

14.833

AU

0.40

0.30

18.726

0.50

0.20

0.10

0.00 0.00

2.00

4.00

6.00

8.00

10.00

12.00

14.00 16.00 Minutes

Peak Results RT 1

Area

Height

% Area

635306

24.26

11177453 563713

26.15

9.078 10369086

2 10.552

3 14.833 10145220 4 18.726

298583

23.73

11052066 239962

25.86

Supplementary Figure 219. SFC spectrum for rac-xestospongiene. 295

18.00

20.00

22.00

24.00

26.00

28.00

30.00

296

10

Supplementary Figure 220. 1H NMR (300 MHz, CDCl3) spectrum for (Ra,R)-4ck.

8

2017-01-16 09:28:22.828 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz

7.295

6.413 6.389 6.365

0.99

6 1.00 1.00

zj-7-177

4

5.316 5.296 5.275 5.255 5.028 5.018 5.007 4.997 4.980 4.970 4.960 3.684 3.613 3.593 3.569 3.546 3.324 3.297

1.00

2.98

0.02

2.98

2.467 2.460 2.438 2.416 2.370 2.360 2.347 2.337 2.325 2.315 2.293 2.134 2.110 2.086 2.061 1.640 1.621 1.609 1.600 1.591 1.541 1.515 1.493 1.460 1.440 1.418 1.396 1.364 1.355 1.330 -0.000

2.02

1.99

2

2.00 8.17

0 PPM

Supplementary Figure 221. 13C NMR (75 MHz, CDCl3) spectrum for (Ra,R)-4ck.

297

173.165

200

2017-01-16 10:12:53.015 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 743 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz

150

zj-7-177

100

51.520

50

35.572 33.072 32.824 28.826 27.631 25.075 23.623

55.978

80.226 77.423 77.000 76.577

93.315 90.291 88.490

138.686

204.187

0

PPM

电 (mv )压

zj-7-177-if-3-100-1-1-214 实验时间:2017-01-17,10:38:27 报告时间:2017-01-17,12:43:29 谱图文件:F:\zhuguangjiong\zj\20170117\zj-7-177-if-3-100-1-1214.org 实验内容简介:

1,500

色谱图(zj-7-177-if-3-100-1-1-214.org)

1,400 1,300 1,200 1,100 1,000

800

13.992

电压(mv)

900

700 600 500 400

100

26.337

15.022

200

18.518

300

0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30

时间(min)

峰号 1 2 3 4

峰名

保留时间

分析结果表 峰高

13.992 15.022 18.518 26.337

总计

峰面积

含量

632933.125 595.728 245.622 688.221

10014403.000 11957.195 4872.408 25650.504

99.5776 0.1189 0.0484 0.2551

634462.696

10056883.107

100.0000

Supplementary Figure 222. HPLC spectrum for (Ra,R)-4ck. 298

电 (mv )压

zj-7-114-if-3-100-1-1-214 实验时间:2017-01-17,11:12:52 报告时间:2017-01-17,12:44:44 谱图文件:F:\zhuguangjiong\zj\20170117\zj-7-114-if-3-100-1-1214.org 实验内容简介:

色谱图(zj-7-114-if-3-100-1-1-214.org)

500 450 400 350

150 100

26.198

200

18.515

250

15.448

14.082

电压(mv)

300

50 0 0 1

2

3 4 5

6

7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30

时间(min)

峰号 1 2 3 4

峰名

保留时间

分析结果表 峰高

14.082 15.448 18.515 26.198

峰面积

含量

224085.547 193008.625 137829.547 81985.172

3595589.250 3533020.000 3136710.500 3084028.500

26.9346 26.4659 23.4971 23.1025

636908.891

13349348.250

100.0000

总计

Supplementary Figure 223. HPLC spectrum for rac-4ck. 299

Supplementary Figure 224. 1H NMR (300 MHz, CDCl3) spectrum for (Ra,R)-5k.

300

10

0.94

8

2017-01-18 15:54:22.937 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz

0.98

6

5.333 5.313 5.292 5.272 5.057 5.046 5.030 5.025 5.009 4.988 1.00 1.00

4

3.634 3.614 3.590 3.567 3.306

zj-7-182

1.00

3.00

2.00

2.03

2

2.01

8.34

0

2.513 2.485 2.462 2.373 2.363 2.353 2.330 2.321 2.309 2.294 2.130 2.106 2.082 2.058 1.663 1.640 1.609 1.601 1.579 1.550 1.523 1.480 1.455 1.433 1.413 1.359 -0.000

7.281 6.411 6.387 6.362

10.373

PPM

Supplementary Figure 225. 13C NMR (75 MHz, CDCl3) spectrum for (Ra,R)-5k.

301

178.873

200

2017-01-18 16:34:27.765 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 668 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz

150

zj-7-182

100

50

35.499 33.072 32.852 28.844 27.649 25.103 23.320

55.951

80.327 77.423 77.000 76.577

93.444 90.163 88.517

138.705

204.279

0

PPM

302

10

Supplementary Figure 226. 1H NMR (300 MHz, CDCl3) spectrum for xestospongiene F.

8

2017-03-19 22:06:57.578 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz

7.360

6.413 6.389 6.364

1.00

5.764 5.745 5.712 5.693 5.683 5.663 5.631 5.610 5.551 5.522 5.484 5.331 5.308 5.285 5.262 5.015 4.992 4.972 4.948 3.612 3.592 3.572 3.551 3.264 2.589 2.586 2.564 2.535 2.504 2.480 2.440 2.416 2.394 2.125 2.101 2.077 2.053 2.017 1.988 1.957 1.602 1.559 1.511 1.481 1.447 1.425 1.324 0.000

6 0.02

2.00

0.02 1.00

zj-8-011

4 0.98 3.00 3.03

2

3.04 8.34

0 PPM

303

Supplementary Figure 227. 1H NMR (300 MHz, CDCl3) extended spectrum for xestospongiene F. 6.5 6.413 6.389 6.364 1.00

6.0 2.00

5.764 5.745 5.712 5.693 5.683 5.663 5.631 5.610 5.551 5.522 5.484

5.5

0.02 0.02

5.331 5.308 5.285 5.262

5.0

5.015 4.992 4.972 4.948 1.00

zj-8-011

4.5 PPM

304

200

Supplementary Figure 228. 13C NMR (75 MHz, CDCl3) spectrum for xestospongiene F.

176.538

150

2017-03-19 22:23:06.187 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 254 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz

100

zj-8-011

50

34.745 32.558 28.568 28.440 28.191 27.327 24.542

56.125

80.741 79.693 77.423 77.000 76.568

88.223

129.430

134.072

138.502

0

PPM

Supplementary Figure 229. Quantitative 13C NMR (75 MHz, CDCl3) spectrum for xestospongiene F.

305

200

176.591

2017-03-20 15:06:05.406 USER: nmr SOLVENT: CDCl3 Experiment = zgig30 Pulse length = 9.500 usec Relaxation delay = 60.000 sec NA = 884 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz

150

138.501 135.560 134.062 129.438 0.02

1.00

88.214

100

zj-8-011-Q

50

34.737 32.558 28.569 28.441 28.202 27.319 24.543

56.126

80.732 79.721 77.432 77.000 76.577

0 PPM

PPM 134.062

0.02

134

1.00

132

130

129.438

138

136

135.560

140

138.501

Supplementary Figure 230. Quantitative 13C NMR (75 MHz, CDCl3) extended spectrum for xestospongiene F. 306

SAMPLE Sample Name: ZJ8011 ADH912200040 Sample Type: Vial: 1:A,4 Injection: 1 Injection Volume: 3.00 ul Run Time: 30.0 Minutes Sample Set Name:20170322

Acquired By: Date Acquired: Acq. Method Set: Date Processed: Processing Method: Channel Name: Proc. Chnl. Descr:

System 2017/3/22 17:32:01 CST chiral_isocratic 2017/3/23 14:19:00 CST 1 PDA Ch1 214 [email protected] nm PDA Ch1 214 [email protected] nm

11.032

0.70

INF O R MA T IO N

0.60

0.50

AU

0.40

0.30

9.576

0.10

21.810

0.20

0.00 0.00

2.00

4.00

6.00

8.00

10.00

12.00

14.00 16.00 Minutes

Peak Results 1 2

RT

Area

Height

% Area

9.576

259455

18854

1.62

11.032 15714231

713261

98.03

2248

0.35

3 21.810

56440

Supplementary Figure 231. SFC spectrum for xestospongiene F. 307

18.00

20.00

22.00

24.00

26.00

28.00

30.00

SAMPLE

0.60

Acquired By: Date Acquired: Acq. Method Set: Date Processed: Processing Method: Channel Name: Proc. Chnl. Descr:

System 2017/3/22 14:45:20 CST chiral_isocratic 2017/3/23 14:07:00 CST 1 PDA Ch1 214 [email protected] nm PDA Ch1 214 [email protected] nm

10.552

9.078

Sample Name: ZJ7-158 adh912214200040 Sample Type: Vial: 1:A,1 Injection: 1 Injection Volume: 5.00 ul Run Time: 30.0 Minutes Sample Set Name:20170213

INF O R MA T IO N

14.833

AU

0.40

0.30

18.726

0.50

0.20

0.10

0.00 0.00

2.00

4.00

6.00

8.00

10.00

12.00

14.00 16.00 Minutes

Peak Results RT 1

Area

Height

% Area

635306

24.26

11177453 563713

26.15

9.078 10369086

2 10.552

3 14.833 10145220 4 18.726

298583

23.73

11052066 239962

25.86

Supplementary Figure 232. SFC spectrum for rac-xestospongiene. 308

18.00

20.00

22.00

24.00

26.00

28.00

30.00

309

12

Supplementary Figure 233. 1H NMR (300 MHz, CDCl3) spectrum for (Ra)-5j.

10

0.79

2015-11-18 19:01:05.359 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 16 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz

8

5.187 5.170 5.156 5.140 5.125

6

zj-4-190

2.00

4

1.98

1.98

2

2.01

12.45

3.02

0

2.508 2.484 2.460 2.339 2.323 2.316 2.308 2.301 2.286 2.263 2.007 1.985 1.966 1.960 1.951 1.946 1.927 1.404 1.381 1.356 1.270 0.903 0.881 0.858 -0.000

10.352

PPM

Supplementary Figure 234. 13C NMR (75 MHz, CDCl3) spectrum for (Ra)-5j.

310

179.774

203.645

200

2015-11-19 22:58:33.819 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 482 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz

150

zj-4-190

100

50

33.127 31.859 29.405 29.294 29.147 29.101 28.826 23.476 22.649 14.082

77.423 77.000 76.577

92.883 89.216

0

PPM

Supplementary Figure 235. 1H NMR (300 MHz, CDCl3) spectrum for (Ra)-4bj.

311

10

8

6

1.98

5.167 5.152 5.148 5.135 5.120 5.115 5.102 4.166 4.143 4.119 4.096

2015-11-19 15:57:11.375 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz

4

2.00

zj-4-198

2.02

2.00

2

2.00

15.36

3.04

0

2.441 2.435 2.414 2.388 2.332 2.311 2.300 2.289 2.276 2.265 2.254 2.248 2.002 1.980 1.964 1.955 1.947 1.939 1.922 1.398 1.378 1.355 1.327 1.282 1.270 1.258 1.235 0.903 0.881 0.858 0.000

PPM

Supplementary Figure 236. 13C NMR (75 MHz, CDCl3) spectrum for (Ra)-4bj.

312

200

173.137

150

2015-11-19 15:57:11.375 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz

100

zj-4-198

50

33.431 31.831 29.386 29.258 29.111 28.844 23.871 22.621 14.183 14.054

60.234

77.423 77.000 76.577

92.488 89.473

203.626

0

PPM

zj-4-198-oz-h-400-1-0.5-214 实验时间:2016-01-04,12:32:12 谱图文件:D:\zhuguangjiong\zj\20160104\zj-4-198-oz-h-400-10.5-214..org

报告时间:2016-01-05,17:42:24

实验内容简介:

色谱图(zj-4-198-oz-h-400-1-0.5-214..org)

1,500 1,400 1,300 1,200 1,100 1,000

800 700 600 15.428

电压(mv)

900

500 400 300 14.068

200 100 0 0

1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

16

17

18

19

20

时间(min)

峰号 1 2

峰名

保留时间

分析结果表 峰高

14.068 15.428

总计

峰面积

含量

21746.184 346879.906

377848.406 14457886.000

2.5469 97.4531

368626.090

14835734.406

100.0000

Supplementary Figure 237. HPLC spectrum for (Ra)-4bj. 313

zj-4-197-oz-h-400-1-0.5-214 实验时间:2016-01-04,11:44:12 谱图文件:d:\zhuguangjiong\zj\20160104\zj-4-197-oz-h-400-10.5-214.org

报告时间:2016-01-05,17:40:22

实验内容简介:

色谱图(zj-4-197-oz-h-400-1-0.5-214.org)

700 650 600 550 500

400 350 300 250 200

15.692

13.642

电压(mv)

450

150 100 50 0 0

1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

16

17

18

19

时间(min)

峰号 1 2

峰名

保留时间

分析结果表 峰高

13.642 15.692

总计

Supplementary Figure 238. HPLC spectrum for rac-4bj. 314

峰面积

含量

197026.484 147035.156

5910192.000 5806109.000

50.4442 49.5558

344061.641

11716301.000

100.0000

315

Supplementary Figure 239. 1H NMR (300 MHz, CDCl3) spectrum for (S,E)-6j. 7.365

12 10

2015-11-28 22:06:24.890 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz

8 6 0.03 0.03

1.03 1.01

zj-5-017

1.00

4 1.04

2.01

2

3.04 12.47

3.07

0 -2 PPM

5.853 5.851 5.831 5.828 5.809 5.805 5.802 5.800 5.780 5.777 5.758 5.754 5.705 5.680 5.669 5.644 5.615 5.534 5.530 5.525 5.511 5.506 5.501 5.483 5.479 5.474 5.459 5.455 5.450 5.295 5.276 5.248 5.220 4.928 4.904 4.880 4.856 2.555 2.552 2.530 2.523 2.521 2.500 2.429 2.408 2.387 2.367 2.342 2.321 2.093 2.071 2.049 2.036 2.027 2.007 1.995 1.981 1.964 1.949 1.938 1.907 1.384 1.359 1.269 0.902 0.881 0.858 0.000

316

6.2

Supplementary Figure 240. 1H NMR (300 MHz, CDCl3) extended spectrum for (S,E)-6j.

6.0 5.8

5.853 5.851 5.831 5.828 5.809 5.805 5.802 5.800 5.780 5.777 5.758 5.754 5.705 5.680 5.669 5.644 5.615 5.534 5.530 5.525 5.511 5.506 5.501 5.483 5.479 5.474 5.459 5.455 5.450 5.295 5.276 5.248 5.220

1.01

5.6

0.03

5.4

1.03

5.2

0.03

5.0 4.928 4.904 4.880 4.856

4.8

1.00

4.6 PPM

Supplementary Figure 241. 13C NMR (75 MHz, CDCl3) spectrum for (S,E)-6j.

317

200

176.759

150

2015-11-28 22:17:52.265 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 174 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz zj-5-017

100

50

31.758 31.528 29.065 28.899 28.780 28.504 28.449 28.375 22.318 13.751

77.423 80.824 77.000 76.577

127.178

135.221

0

PPM

zj-5-017-oj-h-100-1-1-214 实验时间:2016/1/7,15:51:30 谱图文件:d:\zhuguangjiong\zj\20160106\zj-5-017-oj-100-1-1214..org

报告时间:2016/1/7,17:05:14

实验内容简介:

色谱图(zj-5-017-oj-100-1-1-214..org)

500 450 400 350

250 200 15.388

电压(mv)

300

150

13.467

100 50 0 0

1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

16

17

18

19

20

时间(min)

峰号 1 2

峰名

保留时间

分析结果表 峰高

13.467 15.388

总计

峰面积

含量

4963.917 120397.070

83447.000 4552410.500

1.8000 98.2000

125360.987

4635857.500

100.0000

Supplementary Figure 242. HPLC spectrum for (S,E)-6j. 318

zj-5-013-oj-h-100-1-1-214 实验时间:2016/1/7,13:38:12 谱图文件:d:\zhuguangjiong\zj\20160106\zj-5-013-oj-100-1-1214.org

报告时间:2016/1/7,17:01:04

实验内容简介:

色谱图(zj-5-013-oj-100-1-1-214.org)

500 450 400 350

250 200

15.242

12.720

电压(mv)

300

150 100 50 0 0

1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

16

17

18

19

20

时间(min)

峰号 1 2

峰名

保留时间

分析结果表 峰高

12.720 15.242

总计

Supplementary Figure 243. HPLC spectrum for rac-6j. 319

峰面积

含量

176572.141 146212.047

5660659.000 5765820.000

49.5398 50.4602

322784.188

11426479.000

100.0000

320

Supplementary Figure 244. 1H NMR (300 MHz, CDCl3) spectrum for (R)-4-tetradecalactone. 10 7.304

8

2016-01-17 21:52:31.890 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz

6

4.534 4.516 4.509 4.489 4.468 4.464 4.461 4.442

1.00

4

zj-5-093

1.03

1.99

2 1.01 1.05 0.99

16.86

3.04

0 -2

2.558 2.535 2.526 2.503 2.379 2.357 2.335 2.315 2.292 2.270 1.918 1.891 1.876 1.860 1.844 1.828 1.812 1.785 1.776 1.756 1.738 1.726 1.713 1.699 1.682 1.650 1.633 1.619 1.601 1.574 1.556 1.538 1.488 1.463 1.441 1.412 1.377 1.265 0.903 0.882 0.858 -0.000

PPM

Supplementary Figure 245. 13C NMR (75 MHz, CDCl3) spectrum for (R)-4-tetradecalactone.

321

200

177.191

150

2016-01-21 17:42:33.241 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 235 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz zj-5-093

100

50

35.444 29.432 29.386 29.322 29.203 29.166 28.715 27.861 25.094 22.529 13.953

31.749

80.943 77.423 77.000 76.577

0 PPM

Supplementary Figure 246. GC spectrum for (R)-4-tetradecalactone. 322

Supplementary Figure 247. GC spectrum for rac-4-tetradecalactone. 323

324

12

Supplementary Figure 248. 1H NMR (300 MHz, CDCl3) spectrum for (Sa)-5j.

10.150

10

2015-11-19 19:34:04.156 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz

8

0.71

5.187 5.170 5.164 5.156 5.140 5.125

6

zj-4-189

2.00

4

1.99

2.01

2

2.00

12.33

3.06

0

2.508 2.484 2.459 2.338 2.323 2.316 2.307 2.300 2.285 2.005 1.983 1.965 1.958 1.951 1.944 1.925 1.403 1.380 1.355 1.303 1.268 0.902 0.880 0.857 -0.000

7.265

PPM

Supplementary Figure 249. 13C NMR (75 MHz, CDCl3) spectrum for (Sa)-5j.

325

200

179.673

150

2015-11-18 13:13:34.671 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 1019 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz zj-4-189

100

50

33.109 31.859 29.405 29.285 29.138 29.101 28.826 23.485 22.649 14.073

77.423 77.000 76.577

92.883 89.216

203.645

0

PPM

Supplementary Figure 250. 1H NMR (300 MHz, CDCl3) spectrum for (Sa)-4bj.

326

10

7.286

8

2015-11-27 00:06:11.562 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz

5.164 5.149 5.133 5.118 5.102

6

4.166 4.142 4.118 4.094 1.97

zj-4-199

4

2.00 2.00

2.01

2

2.00

15.22

3.00

0

2.438 2.433 2.411 2.387 2.329 2.315 2.311 2.299 2.288 2.275 2.253 2.248 2.002 1.980 1.964 1.956 1.947 1.923 1.407 1.381 1.357 1.329 1.281 1.272 1.257 1.233 0.903 0.882 0.858 -0.000

PPM

Supplementary Figure 251. 13C NMR (75 MHz, CDCl3) spectrum for (Sa)-4bj.

327

200

172.871

150

2015-11-19 19:59:08.109 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 166 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz zj-4-199

100

50

33.302 31.758 29.313 29.184 29.019 28.752 23.770 22.529 14.064 13.917

60.050

77.423 77.000 76.577

92.314 89.372

203.599

0

PPM

zj-4-199-oz-h-400-1-0.5-214 实验时间:2015/11/25,9:50:52 谱图文件:D:\zhuguangjiong\zj\20151125\zj-4-199-oz-h-400-10.5-214..org

报告时间:2015/11/26,18:04:03

实验内容简介:

色谱图(zj-4-199-oz-h-400-1-0.5-214.org)

1,500 1,400 1,300 1,200 1,100 1,000

800 700 600

8.873

电压(mv)

900

500 400 300

9.441

200 100 0 0

1

2

3

4

5

6

7

8

9

10

11

12

13

时间(min)

峰号 1 2

峰名

保留时间

分析结果表 峰高

8.873 9.441

峰面积

含量

403421.063 6165.251

5154801.000 67059.127

98.7158 1.2842

409586.303

5219753.844

100.0000

总计

Supplementary Figure 252. HPLC spectrum for (Sa)-4bj. 328

zj-4-197-oz-h-400-1-0.5-214 实验时间:2015/11/25,9:21:13 谱图文件:d:\zhuguangjiong\zj\20151125\zj-4-197-oz-h-400-10.5-214.org

报告时间:2015/11/26,17:53:25

实验内容简介:

色谱图(zj-4-197-oz-h-400-1-0.5-214.org)

1,500 1,400 1,300 1,200 1,100 1,000

800 700 8.900

600 500 400

9.353

电压(mv)

900

300 200 100 0 0

1

2

3

4

5

6

7

8

9

10

11

12

13

时间(min)

峰号 1 2

峰名

保留时间

分析结果表 峰高

8.900 9.353

总计

Supplementary Figure 253. HPLC spectrum for rac-4bj.

329

峰面积

含量

367626.813 305268.219

4300627.000 4330028.000

49.8297 50.1703

672895.031

8630655.000

100.0000

330

Supplementary Figure 254. 1H NMR (300 MHz, CDCl3) spectrum for (S)-4-tetradecalactone. 10 8

2016-01-15 21:29:04.390 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz

7.304

6

zj-5-090

4.534 4.515 4.509 4.489 4.468 4.464 4.442

0.99

4 1.05

1.99

2 1.01 1.02 0.96 16.73

3.06

0 -2 PPM

2.558 2.534 2.525 2.502 2.379 2.358 2.335 2.315 2.293 2.270 1.918 1.891 1.887 1.860 1.844 1.828 1.818 1.813 1.800 1.786 1.776 1.768 1.756 1.738 1.726 1.713 1.706 1.682 1.650 1.633 1.619 1.601 1.587 1.556 1.538 1.525 1.488 1.441 1.412 1.377 1.265 0.904 0.882 0.859 -0.000

Supplementary Figure 255. 13C NMR (75 MHz, CDCl3) spectrum for (S)-4-tetradecalactone.

331

200

177.182

150

2016-01-23 21:46:52.984 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 276 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz zj-5-090

100

50

31.749 29.432 35.453 29.386 29.322 29.203 29.166 28.715 27.870 25.094 22.529 13.953

80.934 77.423 77.000 76.577

0

PPM

Supplementary Figure 256. GC spectrum for (S)-4-tetradecalactone. 332

Supplementary Figure 257. GC spectrum for rac-4-tetradecalactone.

333

Supplementary Figure 258. 1H NMR (300 MHz, CDCl3) spectrum for (Ra)-5l.

334

10.247

10

0.86

2017-03-17 22:21:04.578 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz

8

5.184 5.169 5.154 5.138 5.123

6

2.00

zj-3-171

4

2.03

1.96

2

2.02

17.14

3.06

0 PPM

2.503 2.480 2.457 2.333 2.311 2.297 2.282 2.004 1.982 1.964 1.958 1.949 1.944 1.925 1.400 1.376 1.353 1.262 0.902 0.880 0.857 -0.000

7.265

Supplementary Figure 259. 13C NMR (75 MHz, CDCl3) spectrum for (Ra)-5l.

335

179.737

200

2015-05-28 19:00:18.625 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 2270 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz

150

zj-3-171

100

50

33.118 31.896 29.635 29.607 29.451 29.331 29.147 29.111 28.835 23.485 22.667 14.082

92.883 89.207 77.423 77.000 76.577

203.645

0

PPM

Supplementary Figure 260. 1H NMR (300 MHz, CDCl3) spectrum for (Ra)-4al.

336

10

8

5.03

7.285 7.279 7.263 7.258 7.251 7.244 7.165

2015-06-04 16:17:03.250 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz

5.084 5.074 5.053 5.035 5.024 5.019 5.009

6

4.00

4

zj-3-184

2

1.98 1.96

2.00

16.69

3.04

0

2.424 2.420 2.398 2.374 2.263 2.258 2.255 2.240 2.230 2.224 2.221 2.219 1.876 1.866 1.851 1.841 1.589 1.299 1.280 1.245 1.221 1.208 1.177 0.822 0.801 0.778 -0.000

PPM

Supplementary Figure 261. 13C NMR (75 MHz, CDCl3) spectrum for (Ra)-4al.

337

172.905

200

spect, CDCl3, Thu Jun 05 13:56:41 2015 USER: nmr SOLVENT: Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 1274 PTS1d = 32768 F1 = 75.476807 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz

150

zj-3-184

100

50

33.362 31.883 29.594 29.438 29.300 29.116 28.841 23.813 22.655 14.090

66.127

77.423 77.000 76.577

92.624 89.398

128.486 128.146

135.995

203.611

0

PPM

zj-3-184-ia-100-0-0.8-214 实验时间:2015/6/16,11:25:47 报告时间:2015/6/18,17:15:45 谱图文件:D:\zhuguangjiong\zj\20150612\zj-3-184-ia-100-0-0.8214.org 实验内容简介:

色谱图(zj-3-184-ia-100-0-0.8-214.org)

1,500 1,400 1,300 1,200 1,100 1,000

800 700

20.003

电压(mv)

900

600 500 400 300

22.417

200 100 0 0

1

2

3

4

5

6

7

8

9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27

时间(min)

峰号 1 2

峰名

保留时间

分析结果表 峰高

20.003 22.417

峰面积

含量

494230.219 9328.662

21830514.000 359993.031

98.3777 1.6223

503558.881

22190507.031

100.0000

总计

Supplementary Figure 262. HPLC spectrum for (Ra)-4al. 338

zj-3-183-ia-100-0-0.8-214 实验时间:2015/6/16,10:34:25 报告时间:2015/6/18,17:14:18 谱图文件:D:\zhuguangjiong\zj\20150612\zj-3-183-ia-100-0-0.8214.org

色谱图(zj-3-183-ia-100-0-0.8-214.org)

22.137

1,000 950 900 850 800 750 700 650 600 550 500 450 400 350 300 250 200 150 100 50 0

20.627

电压(mv)

实验内容简介:

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35

时间(min)

峰号 1 2

峰名

保留时间

分析结果表 峰高

20.627 22.137

总计

Supplementary Figure 263. HPLC spectrum for rac-4al. 339

峰面积

含量

230837.906 199542.828

8070378.500 7934117.000

50.4257 49.5743

430380.734

16004495.500

100.0000

340

Supplementary Figure 264. 1H NMR (300 MHz, CDCl3) spectrum for (S,E)-6l. 10 8

2015-06-05 20:53:39.812 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz

7.344

6 0.02

1.02

0.02

1.00 1.00

4

zj-3-181

1.00

2.00

2

3.05 16.63

3.05

0 PPM

5.851 5.828 5.802 5.777 5.756 5.703 5.680 5.666 5.641 5.618 5.532 5.528 5.523 5.508 5.505 5.500 5.481 5.477 5.472 5.457 5.453 5.449 5.296 5.274 5.245 5.223 4.926 4.902 4.878 4.855 2.554 2.552 2.530 2.522 2.500 2.426 2.405 2.384 2.363 2.340 2.317 2.112 2.093 2.070 2.048 2.022 1.994 1.964 1.937 1.906 1.382 1.359 1.264 0.902 0.880 0.857 -0.000

341

Supplementary Figure 265. 1H NMR (300 MHz, CDCl3) extended spectrum for (S,E)-6l. 5.851 5.828

5.8

5.802 5.777 5.756 1.00

5.703 5.680 5.666

5.6

0.02

5.641 5.618

5.4

1.02

5.532 5.528 5.523 5.508 5.505 5.500 5.481 5.477 5.472 5.457 5.453 5.449

5.296 5.274

5.2

0.02

5.245 5.223

5.0 4.926 4.902 4.878 4.855

4.8

1.00

PPM

Supplementary Figure 266. 13C NMR (75 MHz, CDCl3) spectrum for (S,E)-6l.

342

200

176.796

2015-06-05 21:08:17.078 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 235 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz

150

100

zj-3-181

50

31.822 31.620 29.331 29.304 29.175 29.055 28.844 28.559 28.513 28.430 22.391 13.815

77.423 77.000 80.870 76.568

127.196

135.304

0

PPM

zj-3-181-as-h-95-5-1-214 实验时间:2015-07-21,17:15:31 谱图文件:D:\zhuguangjiong\zj\20150720\zj-3-181-as-h-95-5-1214..org

报告时间:2015-07-21,17:39:04

实验内容简介:

色谱图(zj-3-181-as-h-95-5-1-214..org)

300 280 260 240 220 200

160 140 120

11.602

电压(mv)

180

100 80 60

10.583

40 20 0 0

1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

16

17

时间(min)

峰号 1 2

峰名

保留时间

分析结果表 峰高

10.583 11.602

总计

Supplementary Figure 267. HPLC spectrum for (S,E)-6l. 343

峰面积

含量

3032.685 82252.625

37218.348 2870599.500

1.2799 98.7201

85285.310

2907817.848

100.0000

zj-4-048-as-h-95-5-1-214 实验时间:2015-07-21,15:45:11 谱图文件:d:\zhuguangjiong\zj\20150720\zj-4-048-as-h-95-5-1214.org

报告时间:2015-07-21,17:37:21

实验内容简介:

色谱图(zj-4-048-as-h-95-5-1-214.org)

300 280 260 240 220 200

电压(mv)

180 160 140 120 100

10.570

60 40 20

12.017

80

0 0

1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

16

17

18

19

20

时间(min)

峰号 1 2

峰名

保留时间

分析结果表 峰高

10.570 12.017

总计

Supplementary Figure 268. HPLC spectrum for rac-6l. 344

峰面积

含量

20498.037 17177.754

330317.313 336853.625

49.5101 50.4899

37675.791

667170.938

100.0000

345

10

Supplementary Figure 269. 1H NMR (300 MHz, CDCl3) spectrum for (R)-γ-palmitolactone.

8

6

4.530 4.511 4.485 4.460 4.438

2016-12-29 20:58:25.437 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz

1.00

4

zj-5-044

1.00

2.00

2

1.02 1.02

1.00

20.88

3.05

0

PPM

2.553 2.529 2.520 2.497 2.375 2.353 2.331 2.311 2.289 2.266 1.914 1.888 1.873 1.856 1.825 1.800 1.782 1.767 1.754 1.737 1.712 1.698 1.681 1.649 1.631 1.599 1.581 1.554 1.536 1.487 1.487 1.462 1.444 1.411 1.393 1.262 0.903 0.881 0.858 0.000

7.300

Supplementary Figure 270. 13C NMR (75 MHz, CDCl3) spectrum for (R)-γ-palmitolactone.

346

200

177.136

150

2016-12-29 21:11:55.390 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 201 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz zj-5-044

100

50

31.785 29.515 35.462 29.497 29.396 29.331 29.212 28.715 27.870 25.103 22.548 13.963

80.916 77.423 77.000 76.577

0 PPM

Supplementary Figure 271. GC spectrum for (R)-γ-palmitolactone. 347

Supplementary Figure 272. GC spectrum for rac-γ-palmitolactone. 348

349

12

Supplementary Figure 273. 1H NMR (300 MHz, CDCl3) spectrum for (Ra)-5b.

11.552

0.98

10

2016-05-28 23:15:42.453 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 10 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz

8

6

1.95

5.196 5.187 5.186 5.175 5.170 5.168 5.164 5.155 5.150 5.143 5.139 5.124

zj-6-111

4

2.00

2.00

2

2.00

4.04

3.00

0

PPM

2.504 2.479 2.455 2.335 2.321 2.305 2.297 2.282 2.277 2.260 2.015 1.990 1.974 1.967 1.958 1.934 1.418 1.400 1.390 1.372 1.359 1.347 1.335 1.322 1.301 0.919 0.895 0.871 -0.000

7.273

Supplementary Figure 274. 13C NMR (75 MHz, CDCl3) spectrum for (Ra)-5b.

350

200

179.976

2016-05-28 23:25:28.109 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 153 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz

150

zj-6-111

100

50

13.797

33.109 31.179 28.467 23.439 22.134

77.423 77.000 76.577

92.773 89.198

203.636

0

PPM

351

10

Supplementary Figure 275. 1H NMR (300 MHz, CDCl3) spectrum for (Ra)-4bb.

7.298

8

;blank line 2016-05-31 19:52:22.062 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz

5.166 5.151 5.135 5.119 5.105

6

zj-6-116

4.168 4.144 4.120 4.096 1.98

4

2.00 2.01

2.00

2

2.00

3.11

4.03 3.05

0

PPM

2.440 2.434 2.416 2.412 2.409 2.390 2.387 2.331 2.316 2.300 2.289 2.272 2.254 2.012 1.988 1.975 1.956 1.935 1.420 1.391 1.375 1.363 1.351 1.339 1.330 1.282 1.258 1.235 0.922 0.899 0.876 -0.000

Supplementary Figure 276. 13C NMR (75 MHz, CDCl3) spectrum for (Ra)-4bb.

352

200

173.036

2016-05-31 20:08:51.656 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 262 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz

150

zj-6-116

100

50

14.128 13.779

23.844 22.088

33.394 31.197 28.476

60.161

77.423 77.000 76.577

92.369 89.437

203.636

PPM

zj-6-116-oz-h-100-0-1-214 实验时间:2016-06-07,14:17:17 报告时间:2016-06-07,15:56:32 谱图文件:D:\zhuguangjiong\zj\20160607\zj-6-116-oz-h-100-0-1214.org 实验内容简介:

500

色谱图(zj-6-116-oz-h-100-0-1-214.org)

450 400 350

250 200

27.083

电压(mv)

300

150

24.478

100 50 0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35

时间(min)

峰号 1 2

峰名

保留时间

分析结果表 峰高

24.478 27.083

总计

峰面积

含量

4888.275 116701.664

144705.719 13411313.000

1.0675 98.9325

121589.939

13556018.719

100.0000

Supplementary Figure 277. HPLC spectrum for (Ra)-4bb. 353

zj-6-054-oz-h-100-0-1-214 实验时间:2016-06-07,15:06:15 报告时间:2016-06-07,15:55:26 谱图文件:D:\zhuguangjiong\zj\20160607\zj-6-054-oz-h-100-0-1214..org 实验内容简介:

500

色谱图(zj-6-054-oz-h-100-0-1-214..org)

450 400 350

200 150 100

27.017

250

22.188

电压(mv)

300

50 0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35

时间(min)

峰号 1 2

峰名

保留时间

分析结果表 峰高

22.188 27.017

总计

Supplementary Figure 278. HPLC spectrum for rac-4bb. 354

峰面积

含量

125608.375 91985.625

9041449.000 9218339.000

49.5156 50.4844

217594.000

18259788.000

100.0000

355

Supplementary Figure 279. 1H NMR (300 MHz, CDCl3) spectrum for (R)-4-decalactone. 10 7.305

8

2016-06-27 15:22:23.234 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz

6

4.539 4.520 4.514 4.494 4.474 4.469 4.448

0.98

zj-6-170

4 1.00

1.97

2 1.01 1.02 1.01 8.07

3.00

0 -2

2.562 2.538 2.530 2.507 2.384 2.362 2.340 2.320 2.297 2.275 1.922 1.891 1.864 1.849 1.832 1.822 1.790 1.759 1.742 1.734 1.711 1.686 1.656 1.638 1.624 1.606 1.588 1.561 1.543 1.491 1.465 1.447 1.415 1.395 1.380 1.345 1.337 1.326 1.294 0.911 0.888 0.865 -0.000

PPM

Supplementary Figure 280. 13C NMR (75 MHz, CDCl3) spectrum for (R)-4-decalactone.

356

177.237

200

2016-06-27 16:23:56.890 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 1022 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz

150

zj-6-170

100

50

13.898

35.453 31.519 28.862 28.734 27.879 25.057 22.391

80.971 77.432 77.000 76.577

0 PPM

Data File C:\CHEM32\1\DATA\SIG10089.D Sample Name: zj-6-170 ===================================================================== Acq. Operator : Acq. Instrument : Instrument 1 Location : Vial 1 Injection Date : 7/6/2016 12:49:40 PM Inj Volume : Manually Acq. Method : C:\CHEM32\1\METHODS\DEF_GC-2.M Last changed : 7/6/2016 12:49:39 PM (modified after loading) Analysis Method : C:\CHEM32\1\METHODS\DEF_GC-OFF.M Last changed : 7/7/2016 3:26:54 PM (modified after loading) Sample Info : dex cb

FID1 A, Front Signal (SIG10089.D) pA

250

200

150

50.095

49.595

100

50

0 0

10

20

30

40

50

===================================================================== Area Percent Report ===================================================================== Sorted By : Signal Multiplier: : 1.0000 Dilution: : 1.0000 Use Multiplier & Dilution Factor with ISTDs

Signal 1: FID1 A, Front Signal Peak RetTime Type Width Area Height Area # [min] [min] [pA*s] [pA] % ----|-------|----|-------|----------|----------|--------| 1 49.595 MF R 0.1630 509.24765 50.51576 97.03940 2 50.095 FM R 0.1153 15.53679 1.96476 2.96060 Totals :

524.78444

52.48052

Supplementary Figure 281. GC spectrum for (R)-4-decalactone. Instrument 1 7/7/2016 3:26:57 PM

357

Page

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Data File C:\CHEM32\1\DATA\SIG10088.D Sample Name: zj-6-161-rac ===================================================================== Acq. Operator : Acq. Instrument : Instrument 1 Location : Vial 1 Injection Date : 7/6/2016 11:22:48 AM Inj Volume : Manually Acq. Method : C:\CHEM32\1\METHODS\DEF_GC-2.M Last changed : 7/6/2016 11:22:46 AM (modified after loading) Analysis Method : C:\CHEM32\1\METHODS\DEF_GC-OFF.M Last changed : 7/7/2016 3:25:28 PM (modified after loading) Sample Info : dex cb

FID1 A, Front Signal (SIG10088.D) pA

250

200

150

49.624 49.969

100

50

0 0

10

20

30

40

50

===================================================================== Area Percent Report ===================================================================== Sorted By : Signal Multiplier: : 1.0000 Dilution: : 1.0000 Use Multiplier & Dilution Factor with ISTDs

Signal 1: FID1 A, Front Signal Peak RetTime Type Width Area Height Area # [min] [min] [pA*s] [pA] % ----|-------|----|-------|----------|----------|--------| 1 49.624 BB 0.1094 282.17673 34.66543 50.30196 2 49.969 BB 0.1158 278.78891 32.32484 49.69804 Totals :

560.96564

66.99027

Supplementary Figure 282. GC spectrum for rac-4-decalactone. Instrument 1 7/7/2016 3:25:32 PM

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Supplementary References: 1. Huang, X; Cao, T.; Han, Y.; Jiang, X.; Lin, W.; Zhang, J.; Ma, S. General CuBr2-catalyzed highly enantioselective approach for optically active allenols from terminal alkynols. Chem. Commun. 51, 6956-6959 (2015). 2. Xu, D.; Li, Z; Ma, S. Novozym-435-catalyzed enzymatic separation of racemic propargylic alcohols. A facile route to optically active terminal aryl propargylic alcohols. Tetrahedron Lett. 44, 6343-6346 (2003). 3. Tellitu, I.; Serna, S.; Herrero, M. T.; Moreno, I.; Domínguez, E.; SanMartin, R. Intramolecular PIFA-mediated alkyne amidation and carboxylation reaction. J. Org. Chem. 72, 1526-1529(2007). 4. Zhang, X.; Fu, C.; Yu, Y.; Ma, S. Stereoselective iodolactonization of 4-allenoic acids with efficient chirality transfer: development of a new electrophilic iodination reagent. Chem. Eur. J., 18, 13501-13509 (2012). 5. Barrot, M.; Fabrihs, G.; Camps, F. Synthesis of [l6,16,16-2H3] 11-hexadecynoic acid and [15,15,16,16,16-2H5] (Z, Z)-11,13- hexadecadienoic acid and their use as tracers in a key step of the sex pheromone Biosynthesis of the Processionary Moth. Tetrahedron 50, 9789-9796 (1994). 6. Harris, B. D.; Bhat, K. I.; JoulliB, M. M. Synthetic studies of Detoxin complex II: syntheses of Detoxin B1 and B3. Heterocycles 1986, 24, 1045. 7. Windsor, K.; Genaro-Mattos, T. C.; Kim, H.-Y. H.; Liu, W.; Tallman, K. A.; Miyamoto, S.; Korade, Z.; Porter, N. A. Probing lipid-protein adduction with alkynyl surrogates: application to Smith-Lemli-Opitz syndrome. J. Lipid Res. 54, 2842-2850 (2013). 8. Tungen, J. E.; Aursnes, M.; Hansen, T. V. Stereoselective synthesis of Maresin 1. Tetrahedron Lett. 56, 1843-1846 (2015). 9. Eggleston, D. S.; Chodosh, D. F. Synthesis and X-ray Crystal Structure Determination

of

Two

Pseudopolymorphic

Forms

of

μ-[1,2-bis(diphenylphosphino)ethane] bis [chlorogold(I)]: a Digold(I) DNA Binder. Inorg. Chim. Acta, 108, 221-226 (1985). 10. National Center for Biotechnology Information. PubChem Compound Database;

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CID= 92978644, https://pubchem.ncbi.nlm.nih.gov/compound/92978644. 11. Doolittle R. E.; Tumlinson, J. H.; Proveaux, A. T.; Heath, R. R. Synthesis of the sex pheromone of the Japanese beetle. J. Chem. Ecol. 6, 473-485 (1980). 12. Solladie, G.; Stone, G. B.; Hamdouchi, C. Application of the low-valent Titanium reductive elimination of 1,6-dibenzoate-2,4-dienes to the total synthesis of 6(E)-5(S)-12(R)-Leukotriene B4. Tetrahedron Lett. 34, 1807-1810 (1993). 13. Hulme, A. N.; HowellsStudies, G. E. towards the synthesis of the marine metabolite, Octalaetin A. Tetrahedron Lett. 38, 8245-8248 (1997). 14. Rüttinger, R.; Leutzow, J.; Wilsdorf, M. Wilckens, K.; Czekelius, C. Reversal of selectivity in Gold-catalyzed cyclizations of 3,3-disubstituted 1,4-diynes. Org. Lett. 13, 224-227 (2011). 15. Ma, S.; Liu, J.; Li, S.; Chen, B.; Cheng, J.; Kuang, J.; Liu, Y.; Wan, B.; Wang, Y.; Ye, J.; Yu, Q., Yuan, W.; Yu, S. Development of a general and practical iron nitrate/TEMPO-catalyzed aerobic oxidation of alcohols to aldehydes/ketones: catalysis with table salt. Adv. Synth. Catal. 353, 1005-1017 (2011). 16. Desai, N. B.; Mckelvie, N.; Ramirez, F. A new synthesis of 1,1-dibromoölefins via phosphine-dibromomethylenes. The reaction of triphenylphosphine with carbon tetrabromide. J. Am. Chem. Soc. 84, 1745-1747 (1962). 17. Gannett, P. M.; Nagel, D. L.; Reilly, P. J.; Lawson, T.; Sharpe, J.; Toth, B. The capsaicinoids: their separation, synthesis, and mutagenicity. J. Org. Chem. 53, 1064-1071 (1988). 18. Ardolino, M. J.; Eno, M. S.; Morken, J. P. Stereocontrol in Palladium-catalyzed propargylic substitutions: kinetic resolution to give enantioenriched 1,5-enynes and propargyl acetates. Adv. Synth. Catal. 355, 3413-3419 (2013). 19. Nagamitsu, T.; Takano, D.; Marumoto, K.; Fukuda, T.; Furuya, K.; Otoguro, K.; Takeda, K.; Kuwajima, I.; Harigaya, Y.; Omura, S. Total synthesis of Borrelidin. J. Org. Chem. 72, 2744-2756 (2007). 20. Jiang, W.; Liu, D.; Deng, Z.; Voogd, N. J.; Proksch, P.; Lin, W. Brominated polyunsaturated lipids and their stereochemistry from the Chinese marine sponge Xestospongia testudinaria. Tetrahedron 67, 58-68 (2011).

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21.

Pheromone

synthesis.

Part

249:

Syntheses

of

methyl

(R,E)-2,4,5-tetradecatrienoate and methyl (2E,4Z)-2,4-decadienoate, the pheromone components of the male dried bean beetle, Acanthoscelides obtectus (Say). Tetrahedron 68, 1936-1946 (2012). 22. Krief, A.; Ronvaux, A.; Tuch, A. Catalytic enantioselective synthesis of 2-alkylcyclobutanones and 4-alkyl-γ-butyrolactones from alkylidenecyclopropanes and the sharpless AD-mix reagent. Bull. Soc. Chim. Belg. 106, 699-702 (1997). 23. Leal, W. S.; Kuwahara, S.; Ono, M.; Kubota, S. (R,Z)-7,15-Hexadecadien-4-olide, sex pheromone of the yellowish elongate chafer, heptophylla picea. Bioorg. Med. Chem. 4, 315-321 (1996). 24.

Bravo,

P.;

Resnati,

G.;

Viani,

F.;

Arnone,

A.

Synthesis

of

the

(4S,5R)-5-Hydroxy-decan-4-olide (L-Pactor) and of the (R)-decan-4-olide from a chiral sulphoxide. Tetrahedron 43, 4635-4647 (1987).

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