Synthetic Studies on Tricyclic Diterpenoids: Direct Allylic Amination

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... and Elvira E. Shults*[a, b] open_201500187_sm_miscellaneous_information.pdf ..... 7-ethyl-1,4a,7-trimethyl-9-(phenyl-sulfonamido)-1,2,3,4,4a,4b,5,6,7,9,10 ...
Supporting Information  2016 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Synthetic Studies on Tricyclic Diterpenoids: Direct Allylic Amination Reaction of Isopimaric Acid Derivatives** Mariya A. Timoshenko,[a, b] Yurii V. Kharitonov,[a, b] Makhmut M. Shakirov,[a] Irina Yu. Bagryanskaya,[a, b] and Elvira E. Shults*[a, b]

open_201500187_sm_miscellaneous_information.pdf

SUPPORTING INFORMATION Table of contents

1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12.

S1. Experimental Section S.1.1.Genaral S1.2. Reactions and synthetic procedures S1.3. Strutures, full chemical names, physical characteristics for synthesized of compounds Table S1. 13C NMR Spectral Data for 4-7, 10-13 (CDCl3, δ, ppm) Table S2. 13C NMR Spectral Data for 15, 22-27 (CDCl3, δ, ppm) Table S3. 13C NMR Spectral Data for 28-35 (CDCl3, δ, ppm) Table S4. 13C NMR Spectral Data for 36, 38-40, 42, 44, 45 (CDCl3, δ, ppm) S2. X-ray crystal structure analysis for compounds 5, 24, 27, and 36 Table S5. XRD data for compounds 5, 24, 27 and 36 Table S6. Parameters of the short inter-molecular and the selected intra-molecular contacts for 24, 27, and 36 S3. 1H and 13C spectra of synthesized compounds.

S1. Experimental Section 1

S1.1.General: H NMR and

С NMR spectra were recorded with a Bruker AV-400 ( H: 400.13 MHz, C: 100.78 MHz) or Bruker AV-600 ( H: 600.30 MHz,

13

1

13

1

13

C: 150.95 MHz) (Bruker BioSpin GmbH, Rheinstetten, Germany) instrument in

1 CDCl3, using tetramethylsilane (TMS) as an internal standard. Chemical shifts are reported in ppm downfield from CDCl3 (δ = 7.27 ppm) for H NMR and relative to the central CDCl3 resonance (δ = 77.0 ppm) for 1

spectroscopy. In the description of the H and

13

C NMR

13

C-NMR spectra for compounds 4-7, 10-13, 15, 22-36, 38-40 42, 44, and 45 the tricyclic diterpenoid core atoms numeration system given in structure 2 was used. The following

-1 abbreviations heve been used to denote the multiplicities: s (singlet), d (doublet), t (triplet), q (quartetr), m (multiplet). IR absorption spectra were obtained with a Bruker Vector-22 spectrometer, and values are reported in cm . UV spectra o were obtained with an HP 8453 UV-Vis spectrometer (Hewlett-Packard, Waldbronn, Germany) in EtOH. HRMS spectra were recorded with a DFS spectrometer (Thermo Scientific, evaporator temperature 240-270 C). The melting points were

determined on a Stuart SMF-38 melting point apparatus (Bibby Scientific, Staffordshire, UK) and are uncorrected. Specific rotation [α]D was measured at room (20-23°C) temperature in CHCl3 on a PolAAr 3005 polarimeter. XRD data for compounds 5, 24, 27 were obtained on a Bruker Kappa Apex II CCD diffractometer using φ, ω scans of narrow (0.5°) frames with Mo Kα radiation (λ = 0.71073 Å ) and a graphite monochromator. The structure was solved by direct methods and refined by full-matrix least-squares method against all F2 in anisotropic approximation using the SHELX-97 programs set.[24] The hydrogen atoms positions were calculated with the riding model. Absorption corrections were [25]

applied using the empirical multiscan method with the SADABS program.

The analytical and spectroscopic investigations were carried out at the Collective Use Center for Chemical Services of the Siberian Branch of the Russian

Academy of Sciences. The reaction progress and the purity of the obtained compounds were monitored by TLC on Silufol UV-254 plates (Kavalier, Czech Republic, CHCl3-EtOH, 100:1; detection under UV light or by spraying the plates with 10% water solution o of H2SO4 followed by heating at 100 C). Column chromatography was performed by using silica gel 60 (0.063–0.200 mm, Merck KGaA, Darmstadt, Germany).

All solvents were freshly distilled under argon prior to being used. Anilines 3,8,9,16-21,37, benzenesulfonamide (41) and tert-butyl carbamate (43) were commercially obtained from Aldrich and Alpha Aesar. Methyl 14α-hydroxy-15,16dihydroisopimarate (2) was prepared according to the literature procedure.

[9]

1

S1.2. Reactions and synthetic procedures Reaction of methyl 14α-hydroxy-15,16-dihydroisopimarate (2) with 2-nitroaniline (3). а) 2-Nitroaniline (3) (410 mg, 3.00 mmol) and AuCl3 (9 mg, 0.03 mmol) were added to a solution of methyl 14α-hydroxy-15,16-dihydroisopimarate (2) (500 mg, 1.50 mmol) in CH3CN (10 mL) under stirring. The mixture was stirred at room temperature for 24 h. Then the solvent was evaporated under reduced pressure, and the residue was subjected to chromatography on silica gel using petroleum ether–ether (10 : 1) as eluent to afford diene 5 as a white solid (9 mg, 2%) and compound 4 as an orange oil (640 mg, 90%). b) 2-Nitroaniline (3) (410 mg, 3.00 mmol) and p-toluenesulfonic acid (26 mg, 0.15 mmol) were added to a solution of compound 2 (500 mg, 1.50 mmol) in CH3CN (10 mL). After stirring for 24 h at room temperature, the solvent was removed in vacuo and the residue was subjected to column chromatography on silica gel to .

afford compounds 5 (114 mg, 24%), 6 as a colorless oil (9 mg, 2%), 4 (164 mg, 24%), and 7 as an orange oil (55 mg, 8%). c) 2-Nitroaniline (3) (410 mg, 3.00 mmol) and BF3 Et2O (0.02 ml, 0.15 mmol) were added to a solution of compound 2 (500 mg, 1.50 mmol) in CH3CN (10 mL). After the stirring for 24 h at room temperature, the solvent was evaporated under reduced pressure, and the residue was subjected to chromatography on silica gel to afford compounds 5 (132 mg, 28%), 6 (28 mg, 6%) and 7 (162 mg, 23%). Reaction of methyl 14α-hydroxy-15,16-dihydroisopimarate (2) with 4-nitroaniline (8). 4-Nitroaniline (8) (410 mg, 3.00 mmol) and AuCl3 (9 mg, 0.03 mmol) were added to a solution of compound 2 (500 mg, 1.50 mmol) in CH3CN (10 mL) under stirring. The mixture was stirred at 25 °C for 24 h. The solvent was evaporated under reduced pressure, and the residue was subjected to chromatography on silica gel to afford compounds 10 as an yellow oil (533 mg, 74%) and 11 as an yellow oil (142 mg, 19%). Reaction of methyl 14α-hydroxy-15,16-dihydroisopimarate (2) with 3-nitroaniline (9). а) 3-Nitroaniline (9) (410 mg, 3.0 mmol) and AuCl3 (9 mg, 0.03 mmol) were added under stirring to a solution of compound 2 (500 mg, 1.5 mmol) in CH3CN (10 mL). After the stirring for 24 h at room temperature, the solvent was evaporated under reduced pressure, and the residue was subjected to column chromatography on silica gel to afford compounds 12 as an orange oil (160 mg, 24%), 13 as an yellow oil (40 mg, 6%), 15 as an orange oil (88 mg, 13%), 14 as a white solid (93 mg, 14%), and 2 (120 mg, 24%). b) 3-Nitroaniline (9) (410 mg, 3.0 mmol) and AuCl3 (27 mg, 0.09 mmol) were added under stirring to a solution of compound 2 (500 mg, 1.5 mmol) in CH3CN (10 mL). After the stirring for 24 h at room temperature, the solvent was evaporated under reduced pressure, and the residue was subjected to column chromatography on silica gel in the mentioned conditions to afford compounds 12 (354 mg, 52%), 13 (73 mg, 11%), 15 (149 mg, 22%), 14 (33 mg, 5%), and 2 (40 mg, 8%). c) Methyl 14α-hydroxy-15,16-dihydroisopimarate 2 (500 mg, 1.5 mmol) was dissolved in CH3CN (10 mL) and 3-nitroaniline (9) (410 mg, 3.0 mmol), AuCl3 (9 mg, 0.03 mmol), AgOTf (23 mg, 0.09 mmol) were added in succession under stirring. The mixture was stirred for 24 h at room temperature, the solvent was evaporated under reduced pressure, and the residue was subjected to chromatography on silica gel to afford compounds 12 (347 mg, 51%), 13 (53 mg, 8%), 15 (125 mg, 18%), 14 (60 mg, 9%), and 2 (40 mg, 8%). d) Compound 2 (500 mg, 1.5 mmol) was dissolved in CH3NO2 (5 mL) and 3-nitroaniline (9) (410 mg, 3.00 mmol), AuCl3 (9 mg, 0.03 mmol) and AgOTf (23 mg, 0.09 mmol) were added in succession under stirring. After stirring for 24 h at room temperature, the solvent was removed in vacuo and the residue was subjected to column chromatography on silica gel to afford compounds 12 (428 mg, 63%), 13 (59 mg, 9%), and 15 (132 mg, 19%). e) 3-Nitroaniline (9) (410 mg, 3.00 mmol) and AgOTf (23 mg, 0.09 mmol) were added to a solution of compound 2 (500 mg, 1.50 mmol) in CH3NO2 (5 mL). After the stirring for 24 h at room temperature, the solvent was evaporated under reduced pressure, and the residue was subjected to column chromatography on silica gel to afford compounds 12 (307 mg, 45%), 13 (46 mg, 7%), 15 (105 mg, 16%), 14 (112 mg, 13%), and 2 (65 mg, 13%). f) 3-Nitroaniline (9) (410 mg, 3.0 mmol) and AgBF4 (12 mg, 0.06 mmol) were added to a solution of compound 2 (500 mg, 1.5 mmol) in CH3CN (10 mL). After stirring for 24 h at room temperature, the solvent was evaporated under reduced pressure, and the residue was subjected to column chromatography on silica gel to afford compounds 12 (230 mg, 34%), 13 (27 mg, 4%), 15 (81 mg, 12%), 14 (40 mg, 8%), and 2 (190 mg, 38%). g) 3-Nitroaniline (9) (410 mg, 3.0 mmol), AuClPPh3 (26 mg, 0.03 mmol) and AgBF4 (12 mg, 0.06 mmol) were successfully added to a stirring solution of compound 2 (500 mg, 1.5 mmol) in CH3CN (10 mL). After stirring for 24 h at room temperature, the solvent was evaporated under reduced pressure, and the residue was subjected to column chromatography to afford compounds 12 (290 mg, 38%), 13 (28 mg, 8%), 15 (102 mg, 15%), 14 (70 mg, 14%), and 2 (115 mg, 23%). h) Compound 2 (500 mg, 1.5 mmol) was dissolved in CH3CN (10 mL) and 3nitroaniline (9) (410 mg, 3.0 mmol), AuClPPh3 (26 mg, 0.03 mmol) and AgOTf (11 mg, 0.03 mmol) were added under stirring. The mixture was stirred for 24 h at room temperature, then the solvent was removed in vacuo, and the residue was subjected to column chromatography to afford compounds 12 (217 mg, 32%), 13 (34 mg, 5%), 15 (82 mg, 12%), 14 (75 mg, 15%), and 2 (100 mg, 20%). i) 3-Nitroaniline (9) (410 mg, 3.00 mmol), AuClPPh3 (26 mg, 0.03 mmol) and AgOTf (23 mg, 0.09 mmol) were added in succession to a stirred solution of compound 2 (500 mg, 1.5 mmol) in CH3CN (10 mL). The mixture was stirred for 24 h, then the solvent was removed under reduced pressure, and the residue was subjected to column chromatography to afford compounds 12 (279 mg, 41%), 13 (60 mg, 9%), 15 (111 mg, 16%), 14 (40 mg, 6%), and 2 (20 mg, 4%). Reaction of methyl 14α-hydroxy-15,16-dihydroisopimarate (2) with 2-bromoaniline (16). a) Compound 2 (500 mg, 1.5 mmol) was dissolved in CH3NO2 (5 mL) and 2-bromoaniline (16) (380 mg, 3.0 mmol), AuCl3 (9 mg, 0.03 mmol) and AgOTf (23 mg, 0.09 mmol) were added in succession under stirring. The mixture was stirred for 24 h at room temperature, the solvent was evaporated under reduced pressure, and the residue was subjected to column chromatography on silica gel to afford compounds 22 as a colorless oil (388 mg, 53%), 28 as a colorless oil (73 mg, 10%), and 29 as a colorless oil (44 mg, 6%). b) To a stirring solution of compound 2 (500 mg, 1.5 mmol) in CH3CN (10 mL) 2-bromoaniline 16 (380 mg, 3.0 mmol), AuCl3 (9 mg, 0.03 mmol) and AgOTf (23 mg, 0.09 mmol) were added in succession under. The mixture was stirred for 24 h at room temperature, them the solvent was removed in vacuo, and the residue was subjected to column chromatography on silica gel to afford compounds 5 (10 mg, 2%), 6 (5 mg, 1%), 22 (284 mg, 39%), 30 as a colorless oil (139 mg, 19%), 31 as a colorless oil (117 mg, 16%), 14 (65 mg, 13%), and 2 (50 mg).

2

(1R,4aR,4bR,7S,9R,10aR)-Methyl 9-((2-chloro-4-nitrophenyl)amino)-7-ethyl-1,4a,7-trimethyl-1,2,3,4,4a,4b,5,6,7,9,10,10a-dodecahydrophenan-threne-1-carboxylate (23). Compound 2 (500 mg, 1.5 mmol) was dissolved in CH3CN (10 mL) and 2-chloro-4-nitroaniline (17) (520 mg, 3.0 mmol), AuCl3 (9 mg, 0.03 mmol), and AgOTf (23 mg, 0.09 mmol) were added in succession under stirring. The mixture was stirred for 24 h at room temperature, the solvent was removed under reduced pressure, and the residue was subjected to column chromatography on silica gel to afford diene 6 (66 mg, 14%) and compound 23 as a yellow oil (381 mg, 52%). (1R,4aR,4bR,7S,9R,10aR)-Methyl 7-ethyl-9-((4-methoxy-2-nitrophenyl)-amino)-1,4a,7-trimethyl-1,2,3,4,4a,4b,5,6,7,9,10,10a-dodecahydrophenan-threne-1-carboxylate (24). Compound 2 (500 mg, 1.5 mmol) was dissolved in CH3CN (10 mL) and 4-methoxy-2-nitroaniline (18) (504 mg, 3.0 mmol), AuCl3 (9 mg, 0.03 mmol) and AgOTf (23 mg, 0.09 mmol) were added in succession under stirring. The mixture was stirred for 24 h at room temperature, the solvent was removed under reduced pressure, and the residue was subjected to chromatography on silica gel to afford dienes 5 (24 mg, 5%), 6 (14 mg, 3%), and compound 24 as a red powder (589 mg, 81%). (1R,4aR,4bR,7S,9R,10aR)-Methyl 7-ethyl-1,4a,7-trimethyl-9-((3-(trifluoromethyl)phenyl)amino)-1,2,3,4,4a,4b,5,6,7,9,10,10a-dodecahydro-phenanthrene-1-carboxylate (25). To a stirred solution of compound 2 (500 mg, 1.5 mmol) and 3-(trifluoromethyl)aniline (18) (483 mg, 3.0 mmol) in CH3NO2 (5 mL) AuCl3 (9 mg, 0.03 mmol), and AgOTf (23 mg, 0.09 mmol) were added. The mixture was stirred for 24 h at room temperature, the solvent was removed under reduced pressure, and the residue was subjected to column chromatography on silica gel to afford compounds 5 (9 mg, 2%), 6 (9 mg, 2%), 25 as a colorless oil (343 mg, 48%), 33 as a pale yellow oil (93 mg, 13%), and 32 as a pale yellow oil (143 mg, 20%). (1R,4aR,4bR,7S,9R,10aR)-Methyl 7-ethyl-1,4a,7-trimethyl-9-((4-(trifluoromethyl)phenyl)-amino)-1,2,3,4,4a,4b,5,6,7,9,10,10a-dodeca-hydrophenanthrene-1-carboxylate (26). Compound 2 (500 mg, 1.5 mmol) was dissolved in CH3CN (10 mL) and 4-(trifluoromethyl)aniline 20 (483 mg, 3.0 mmol), AuCl3 (9 mg, 0.03 mmol), and AgOTf (23 mg, 0.09 mmol) were added in succession under stirring. The mixture was stirred for 24 h at room temperature, the solvent was removed under reduced pressure, and the residue was subjected to column chromatography on silica gel to afford compounds 26 as a pale yellow oil (501 mg, 70%), 35 (100 mg, 14%), 34 as a pale yellow oil (100 mg, 14%), and 14 (30 mg, 6%). (1R,4aR,4bR,7S,9R,10aR)-Methyl 9-((4-acetylphenyl)amino)-7-ethyl-1,4a,7-trimethyl-1,2,3,4,4a,4b,5,6,7,9,10,10a-dodecahydrophenanthrene-1-carboxylate (27). Compound 2 (500 mg, 1.5 mmol) was dissolved in CH3NO2 (5 mL) and 1-(4-aminophenyl)ethanone 21 (400 mg, 3.0 mmol), AuCl3 (9 mg, 0.03 mmol), and AgOTf (23 mg, 0.09 mmol) were added in succession under stirring. The mixture was stirred at 25 °C for 24 h. The solvent was distilled off under reduced pressure, and the residue was subjected to column chromatography on silica gel to afford compounds 27 as an orange oil (454 mg, 67%) and 36 (76 mg, 11%). (1R,4aR,4bR,7S,9S,10aR)-Methyl 7-ethyl-1,4a,7-trimethyl-9-(methyl(4-nitrophenyl)-amino)-1,2,3,4,4a,4b,5,6,7,9,10,10a-dodecahydrophenan-threne-1-carboxylate (38). Compound 2 (500 mg, 1.5 mmol) was dissolved in CH3CN (10 mL) and N-methyl-4-nitroaniline (37) (456 mg, 3.00 mmol), AuCl3 (9 mg, 0.03 mmol), and AgOTf (23 mg, 0.09 mmol) were added in succession under stirring. The mixture was stirred for 24 h at room temperature, the solvent was removed under reduced pressure, and the residue was subjected to column chromatography to afford compounds 5 (149 mg, 31%), 6 (14 mg, 3%), 38 as an yellow oil (126 mg, 18%), and 39 as a colorless oil (148 mg, 15%). (1R,4aR,4bR,7S,9S,10aR)-Methyl 7-ethyl-1,4a,7-trimethyl-9-((4-nitrophenyl)amino)-1,2,3,4, 4a,4b,5,6,7,9,10,10a-dodecahydrophenanthrene-1-carboxylate (40). Dimer 39 (500 mg, 0.77 mmol) was dissolved in CH3NO2 (5 mL) and 4-nitroaniline (8) (212 mg, 1.54 mmol), AuCl3 (5 mg, 0.02 mmol), and AgOTf (11 mg, 0.05 mmol) were added in succession under stirring. The mixture was stirred for 24 h at room temperature, the solvent was removed under reduced pressure, and the residue was subjected to column chromatography to afford compounds 5 (185 mg, 38%), 10 (160 mg, 23%), and 40 as an yellow oil (160 mg, 23%). (1R,4aR,4bR,7S,9R,10aR)-Methyl 7-ethyl-1,4a,7-trimethyl-9-(phenyl-sulfonamido)-1,2,3,4,4a,4b,5,6,7,9,10,10a-dodecahydrophenanthrene-1-carboxylate (42). Compound 2 (500 mg, 1.50 mmol) was dissolved in CH3CN (10 mL) and benzenesulfonamide (41) (472 mg, 3.00 mmol), AuCl3 (5 mg, 0.02 mmol), and AgOTf (11 mg, 0.05 mmol) were added in succession under stirring. The mixture was stirred for 24 h at room temperature, the solvent was removed under reduced pressure, and the residue was subjected to column chromatography on silica gel to afford compounds 5 (57 mg, 12%), 6 (28 mg, 6%), and 42 as a white solid (291 mg, 41%). (1R,4aR,4bR,7S,9R,10aR)-Methyl 9-((tert-butoxycarbonyl)amino)-7-ethyl-1,4a,7-trimethyl-1,2,3,4,4a,4b,5,6,7,9,10,10a-dodecahydrophenanthrene-1-carboxylate (44). Compound 2 (500 mg, 1.5 mmol) was dissolved in CH3NO2 (5 mL) and tert-butyl carbamate (43) (351 mg, 3.00 mmol), AuCl3 (9 mg, 0.03 mmol), and AgOTf (23 mg, 0.09 mmol) were added in succession under stirring. The mixture was stirred for 24 hat room temperature, the solvent was removed under reduced pressure, and the residue was subjected to column chromatography on silica gel to afford compound 44 as a colorless oil (422 mg, 65%). (1R,4aR,4bR,7S,9R,10aR)-Methyl 9-amino-7-ethyl-1,4a,7-trimethyl-1,2,3,4,4a,4b,5,6,7,9,10,10a-dodecahydrophenanthrene-1-carboxylate (45). Compound 44 (500 mg, 1.5 mmol) was dissolved in CH3OH (10 mL) and 1.5 mL of concentrated HCl was added under stirring at 20°C and the mixture was left to stand for 24 h at 20°C, then treatment by adding of 0.5 mL of triethylamine. The solvent was evaporated under reduced pressure. Water (5 mL) was added

3

and extractions with CH2Cl2 (4 × 10 mL) was performed. The combined organic Layers were dried with magnesium sulfate, filtrated and concentrated in vacuo. The oily residue was purified by column chromatography on silica gel using petroleum ether-methanol (10 : 1) as an eluent, to afford compound 45 as a colorless oil (450 mg, 90%). Treatment of 2 with AuCl3 in CH3CN. A solution of compound 2 (500 mg, 1.5 mmol) in CH3CN (10 mL) was treated by AuCl3 (9 mg, 0.03 mmol). After stirring of the mixture for 24 h at ambient temperature, the solvent was removed under reduced pressure, and the residue was subjected to column chromatography on silica gel to afford compounds 5 (50 mg, 8%), 39 (148 mg, 15%), 14 (140 mg, 28%), and 2 (180 mg). Treatment of 2 with AuCl3-AgOTf in CH3NO2. Compound 2 (500 mg, 1.50 mmol) was dissolved in CH3NO2 (5 mL) and AuCl3 (9 mg, 0.03 mmol) and AgOTf (23 mg, 0.09 mmol) were added under stirring. The mixture was stirred for 24 h at room temperature, the solvent was removed under reduced pressure, and the residue was subjected to column chromatography to afford dienes 5 (144 mg, 23%), 6 (325 mg, 69%) and starting compound 2 (11 mg). Reaction of methyl 7α-hydroxy-15,16-dihydrosandaracopimarate (14) with 3-nitroaniline (9). Compound 14 (500 mg, 1.50 mmol) was dissolved in CH3NO2 (5 mL) and 3-nitroaniline (9) (410 mg, 3.00 mmol), AuCl3 (9 mg, 0.03 mmol), and AgOTf (23 mg, 0.09 mmol) were added in succession under stirring. The mixture was stirred for 24 h at room temperature, the solvent was removed under reduced pressure, and the residue was subjected to column chromatography to afford compounds 12 (347 mg, 51%), 13 (46 mg, 7%), 15 (105 mg, 15%), and 14 (100 mg, 13%). X-ray crystal structure analysis for compounds 5, 24, 27, and 36: The compounds 24, 27 crystallizes in the orthorhombic space groups P212121, while 5, 36 crystallizes in the monoclinic P21 group. The crystallographic data are listed in Table S5. Molecular structure of compounds 6, 24, 27, 36 is illustrated in Fig. 2. The obtained crystal structures were analyzed for short contacts between non-bonded atoms using PLATON [26] and MERCURY programs [27]. CCDC 1407201 (5), 1407203 (24), 1407202 (27), 1422327 (36) contain the supplementary crystallographic data for this paper. These data can be obtained free of charge via http://www.ccdc.cam.ac.uk/cgi-bin/catreq.cgi, or from the Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: (+44) 1223 336 033; or e-mail: [email protected].

S1.3. S1.3. Strutures, full chemical names, physical characteristics for synthesized of compounds

(1R,4aR,4bR,7S,9R,10aR)-Methyl 7-ethyl-1,4a,7-trimethyl-9-[(2-nitro-phenyl)amino]-1,2,3,4,4a,4b,5,6,7,9,10,10a-dodecahydrophenanthrene-1-carboxylate (4). 1177 111 99

220 22 3

11

10

133 14

6

H 18

Rf = 0.60 (CHCl3); [α]D = - 40.8 (c = 6.0, CHCl3); 1H NMR (600 MHz, CDCl3): δ = 0.74 (t, J = 7.4 Hz, 3 H, СН3-16), 0.87 (s, 3 Н, СH3-20), 0.92 (s, 3 H, СН3-17), 1.18-1.28

1166

(m, 2 Н, Н-1,12), 1.20 (s, 3 H, СН3-19), 1.23 (m, 2 Н, CH2-15), 1.30 (m, 1 Н, H-12), 1.46 (m, Jgem = 13.5 Hz, 1 H, Н-6), 1.52-1.58 (m, 4 Н, CH2-2, CH2-11), 1.62 (m, 1 Н, Н-

NO22 N

77

' 22'

NH H 1''

Mee CO22M

119

155

H 88

5

4

122

'

6'

44

'

3), 1.72 (m, 1 Н, Н-3), 1.78 (m, 1 Н, Н-1), 1.79 (ddd, Jgem= 13.5, J = 12.0, 3.8 Hz, 1 Н, Н-6), 2.08 (dd, J = 8.6, 1.8 Hz, 1 Н, Н-9), 2.33 (dd, J = 12.0, 1.8 Hz, 1 Н, Н-5), 3.36

33'

(s, 3 Н, ОСН3), 4.16 (brd, JH7-NH = 6.0 Hz, 1 Н, Нb-7), 5.59 (brs, 1 Н, Н-14), 6.56 (t, J = 8.5 Hz, 1 Н, Н-4’), 6.89 (d, J = 8.5 Hz, 1 Н, Н-6’), 7.35 (t, J = 8.5 Hz, 1 Н, Н-5’),

4''

8.14 (d, J = 8.5 Hz, 1 Н, Н-3’), 8.48 (d, J = 6.0 Hz, 1 Н, NH).

55''

13

C NMR (151 MHz, CDCl3): see Table S1. IR (neat): ν˜ =746, 1035, 1145, 1190, 1244, 1259, 1278, 1338,

1352, 1419, 1444, 1460, 1506, 1571, 1616, 1724, 2848, 2868, 2925, 2949 cm–1. UV (EtOH) λmax nm (lgε): 236 (3.99), 282 (4.22), 434 (3.40). MS (EI): m/z (%) = 454 (9)

[M ], 317 (39), 287 (23), 257 (100), 227 (12), 145 (11), 121 (20), 105 (11), 95 (11), 84 (16), 82 (25), 57 (13); calcd. for C27H38O4N2: 454.2826, found 454.2829. (1R,4aR,4bR,7S,10aR)-Methyl 7-ethyl-1,4a,7-trimethyl-1,2,3,4,4a,4b,5,6, 7,10a-decahydrophenanthrene-1-carboxylate (5). Compound 5 was crystallized from MeOH, m.p. 58-60oС. Rf = 0.66 (CHCl3); [α]D = + 23.81 (c 0.2, СНCl3); 1H NMR (600 MHz, CDCl3): δ = 0.72 (s, 3 Н, СH3-20), 0.79 (t, J

17 12 111 1 13 144

200 2

33

11 4

9

10 5

H

19

6

88 7

e C O2Me 1 2

188

5

= 7.5 Hz, 3 H, СН3-16), 0.91 (s, 3 H, СН3-17), 1.12 (dd, J = 12.8, 4.0 Hz, 1 Н, Н-1), 1.19 (s, 3 H, СН3-19), 1.27 (m, 2 Н, CH2-15), 1.35 (m, 2 Н, H-12,11), 1.39 (m, 1 Н, H15

16

4

12), 1.48-1.61 (m, 3 Н, H-2,11,3), 1.64 (m, 1 Н, Н-2), 1.70 (m, Jgem = 12.8 Hz, 1 H, Н-1), 1.74 (m, 1 Н, Н-3), 2.01 (m, 1 Н, Н-9), 2.69 (s, 1 Н, Н-5), 3.65 (s, 3 Н, ОСН3), 5.25 (m, 2 Н, Н-6,14), 5.95 (dd, J = 9.8, 2.9 Hz, 1 Н, H-7). 13C NMR (151 MHz, CDCl3): see Table S1. IR (neat): ν˜ =1112, 1149, 1188, 1244, 1384, 1434, 1460, 1616, 1728, 2850, 2866, 2935, 3012 cm–1. UV (EtOH) λmax nm (lgε): 236 (4.23), 242 (4.25). MS (EI): m/z (%) = 316 (42), 288 (22), 287 (100), 256 (26), 241 (28), 227 (60), 145 (39), 105 (22), 95 (23), 55 (10); calcd. for C21H32O2: 316.2397, found 316.2392.

(1R,4aS,7S,10aR)-Methyl 7-ethyl-1,4a,7-trimethyl-1,2,3,4,4a,5,6,7,8,10a-decahydrophe-nanthrene-1-carboxylate (6). 17 12 11 12 13 14

220 1

2 3

9

10 5

4

Rf = 0.66 (CHCl3); 1H NMR (400 MHz, CDCl3): δ = 0.77 (t, J = 7.5 Hz, 3 H, СН3-16), 0.78 (s, 3 Н, СH3-20), 0.96 (s, 3 H, СН3-17), 1.14-1.25 (m, 3 Н, CН2-15, H-1), 1.23 (s, 16

1155

Н, H-6,7). 13C NMR (101 MHz, CDCl3): see Table S1. IR (neat): ν˜ =866, 1149, 1244, 1384, 1433, 1460, 1616, 1728, 2850, 2866, 2925 cm–1. UV (EtOH) λmax nm (lgε): 241

8 7

6

3 H, СН3-19), 1.40 (m, 2 H, CH2-12), 1.55-1.62 (m, 3 Н, CH2-2, H-3), 1.72 (m, 2 Н, H-1,3), 1.84-197 (m, 4 Н, CН2-14,11), 3.61 (s, 3 Н, ОСН3), 3.65 m, 1 Н, Н-5), 5.33 (m, 2

(3.92). MS (EI): m/z (%) = 316.2 (2), 241 (2), 87 (10), 85 (66), 83 (100) 50 (7), 48 (11), 47 (22), 35 (10); calcd. for C21H32O2: 316.2397, found 316.2393.

H H

e CO2M e

19

6

18

(1R,4aR,4bR,7S,9S,10aR)-Methyl 9-(4-amino-3-nitrophenyl)-7-ethyl-1,4a,7-trimethyl-1,2,3,4,4a,4b,5,6,7,9,10,10a-dodecahydrophenanthrene-1-carboxylate (7). 177

Rf = 0.44 (CHCl3); [α]D = - 43.3 (c 6.0, CHCl3); 1H NMR (600 MHz, CDCl3): δ = 0.84 (t, J = 7.3 Hz, 3 H, СН3-16), 0.89 (s, 3 Н, СH3-20), 0.95 (s, 3 H, СН3-17), 1.03 (m, 1

112

13 111 144 9

200 2

1

33

110

44

H

55

6'

CO2 Mee

7

6.72 (d, J = 8.7 Hz, 1 Н, Н-5’), 7.26 (dd, J = 8.7, 1.8 Hz, 1 Н, Н-6’), 8.01 (d, J = 1.8 Hz, 1 Н, Н-2’).

'

55'

' 1'

H H

Hz, 1 Н, Н-5), 1.88 (m, 1 Н, Н-9), 1.94 (ddd, J = 13.0, 12.5, 5.4 Hz, 1 Н, Н-6), 3.40 (d, J = 5.4 Hz, 1 Н, Н-7), 3.52 (s, 3 Н, ОСН3), 5.42 (s, 1 Н, Н-14), 5.95 (brs, 2 Н, NH2),

6'

7

6

Н, Н-1), 1.21 (s, 3 H, СН3-19), 1.34 (m, 2 Н, CH2-15), 1.40 (m, 2 Н, CH2-12), 1.49 (m, 3 Н, H-2,11,3), 1.63 (m, 3 Н, H-2,11,6), 1.67 (m, 2 Н, Н-3,1), 1.74 (dd, J = 12.6, 2.0

16

15

8

'

2'

'

44'

33''

C NMR (151 MHz, CDCl3): see Table S1 (Supp. Info). IR (neat): ν˜

13

=758, 1099, 1143, 1172, 1188, 1252, 1340, 1387, 1407, 1460, 1517, 1562, 1591, 1633, 1724, 2850, 2869, 2945, 3489, 3365, 3489 cm –1. UV (EtOH) λmax nm (lgε): 236 NH2

O2 NO

(4.3), 281 (3.7), 420 (2.5). MS (EI): m/z (%) = 454 (100), 454 (100), 426 (18), 425 (60), 365 (69), 287 (40), 227 (29), 151 (55), 121 (41), 95 (29), 85 (29), 83 (45); calcd. for C27H38O4N2: 454.2829, found 454.2821.

(1R,4aR,4bR,7S,9R,10aR)-Methyl 7-ethyl-1,4a,7-trimethyl-9-[(4-nitro-phenyl)amino]-1,2,3,4,4a,4b,5,6,7,9,10,10a-dodecahydrophenanthrene-1-carboxylate (10). Rf = 0.66 (CHCl3); [α]D = + 54 (c 0.5, CHCl3); 1H NMR (400 MHz, CDCl3): δ = 0.78 (t, J = 7.2 Hz, 3 H, СН3-16), 0.86 (s, 3 Н, СH3-20), 0.92 (s, 3 H, СН3-17), 1.18 (m, 2 Н, Н1,12), 1.21 (s, 3 H, СН3-19), 1.25 (m, 2 Н, CH2-15), 1.31 (m, 1 Н, H-12), 1.43 (m, 1 Н, Н-6), 1.55, 1.59, 1.62, 1.66 (all m, 6 Н, CH2-2,11,3), 1.75 (m, 1 Н, Н-1), 1.77 (ddd, J =

1177 11 9

20 2 33

119

1 44

110

1122

113 144

115

13.4, 12.4, 4.2 Hz, 1 Н, Н-6), 2.02 (m, 1 Н, Н-9), 2.25 (dd, J = 12.4, 1.6 Hz, 1 Н, Н -5), 3.45 (s, 3 Н, ОСН3), 4.00 (dd, J = 4.2, 6.0 Hz, 1 Н, Н-7), 4.97 (d, J = 6.0 Hz, 1 Н,

166

NH), 5.62 (s, 1 Н, Н-14), 6.56 (d, J = 8.6 Hz, 2 Н, Н-2’,6’), 8.04 (d, J = 8.6 Hz, 2 Н, Н-3’,5’).

H 8

5

H H

7 6

O22Mee CO

188

NH 11''

1100

C NMR (101 MHz, CDCl3): see Table S1. IR (neat): ν˜ = 833, 1065, 1084,

13

1111, 1188, 1242, 1275, 1320, 1474, 1504, 1526, 1599, 1726, 2853, 2945, 3385 cm . UV (EtOH) λmax nm (lgε): 235 (3.91), 394 (4.32). MS (EI): m/z (%) = 454 (8) [M ]+, –1

2'' '

3'

'

66'

5''

' NO 22 44' N

5

318 (8), 317 (34), 287 (9), 285 (7), 258 (23), 257 (100), 227 (6), 201 (6), 173 (7), 159 (5), 147 (5), 145 (7), 135 (6), 133 (6), 131 (4), 123 (5), 121 (29), 119 (7), 109 (6), 108 (9), 107 (8), 105 (11), 95 (8), 93 (9), 91 (8), 81 (7), 79 (7), 77 (3), 69 (4), 67 (5), 55 (9), 41 (6). HRMS calcd. for C27H38O4N2: 454.2826, found 454.2818

(1R,4aR,4bR,7S,8S,10aR) Methyl 7-ethyl-1,4a,7-trimethyl-8-((4-nitro-phenyl)amino)-1,2,3,4,4a,4b,5,6,7,8,10,10a-dodecahydrophenanthrene-1-carboxylate (11). Rf = 0.66 (CHCl3); [α]D = + 254 (c 0.2, CHCl3); 1H NMR (600 MHz, CDCl3): δ = 0.74 (t, J = 7.5 Hz, 3 H, СН3-16), 0.86 (s, 3 Н, СH3-17), 0.89 (s, 3 H, СН3-20), 1.06 (m, 1 Н,

1177

2 33

1

113 144

11 9

110

H 8

5

44

115

= 12.9 Hz, 1 Н, Н-1), 1.97 (m, 1 Н, Н-9), 3.54 (s, 3 Н, ОСН3), 3.57 (brd, J = 5.6 Hz, 1 Н, Н-14), 4.60 (d, J = 5.6 Hz, 1 Н, NH), 5.61 (d, J = 5.9 Hz, 1 Н, Н-7), 6.53 (d, J = 8.6

166 '

2'

11''

N HN

H

C NMR (151 MHz, CDCl3): see Table S1. IR (neat): ν˜ = 754, 833, 1065, 1111, 1146, 1188, 1246, 1267, 1308, 1435,

13

1474, 1503, 1531, 1599, 1711, 1722, 2855, 2870, 2928, 3379 cm–1. UV (EtOH) λmax nm (lgε): 235 (3.9), 396 (4.2). MS (EI): m/z (%) = 454 (15) [M ]+, 318 (13), 317 (57),

66''

188

Hz, 2 Н, Н-2’,6’), 8.03 (d, J = 8.6 Hz, 2 Н, Н-3’,5’).

3''

7 6

O22Mee CO

119

Н-1), 1.22 (s, 3 H, СН3-19), 1.29 (m, 2 Н, H-15), 1.36-1.46 (m, 4 Н, CH2-12, H-11,2), 1.50-1.61 (m, 6 Н, CH2-6,3, H-2,11), 1.73 (dd, J = 12.1, 4.0 Hz, 1 Н, H-5), 1.82 (m, Jgem

1122

20

NO22 44'' N

'

5'

1111

287 (13), 258 (23), 257 (100), 227 (7), 225 (7), 173 (8), 145 (8), 121 (20), 119 (10), 105 (10), 95 (7), 93 (7), 91 (8), 55 (11), 41 (6); calcd. for C27H38O4N2: 454.2827, found 454.2818.

(1R,4aR,4bR,7S,9R,10aR)-Methyl 7-ethyl-1,4a,7-trimethyl-9-((3-nitrophe-nyl)amino)-1,2,3,4,4a,4b,5,6,7,9,10,10a-dodecahydrophenanthrene-1-carboxylate (12). Rf = 0.62 (CHCl3); [α]D = + 8.56 (c 7.8, СНCl3); 1H NMR (400 MHz, CDCl3): δ = 0.73 (t, J = 7.5 Hz, 3 H, СН3-16), 0.86 (s, 3 Н, СH3-20), 0.90 (s, 3 H, СН3-17), 1.16 (m, 2 Н, Н-

117 111 99

220 22 3

11

10

133 14 15

= 8.3 Hz, 1 Н, Н-6’), 7.21 (t, J = 8.3 Hz, 1 Н, Н-5’), 7.44 (m, 3 Н, Н-2’,4’,NH).

7 6 7

188

2''

H 1'' NH

H H Mee CO22M

19

J = 13.2, 12.2, 4.0 Hz, 1 Н, Н-6), 2.02 (m, 1 Н, Н-9), 2.28 (dd, J = 12.2, 2.2 Hz, 1 Н, Н-5), 3.47 (s, 3 Н, ОСН3), 3.93 (dd, J = 5.6, 3.4, 1 Н, Н-7), 5.63 (s, 1 Н, Н-14), 6.88 (d, J

116

H 88

5

4

1,12), 1.21 (s, 3 H, СН3-19), 1.24 (m, 2 Н, CH2-15), 1.31 (m, 1 Н, H-12), 1.43 (m, 1 Н, Н-6), 1.52-1.60 (m, 4 Н, CH2-2,11), 1.65 (m, 2 Н, CН2-3), 1.74 (m, 1 Н, Н-1), 1.78 (ddd,

12

NO2 3''

6''

12

11 9

22 3

119

1 44

100

'

5'

454.2822. (1R,4aR,4bR,7S,9S,10aR)-Methyl 7-ethyl-1,4a,7-trimethyl-9-((3-nitrophe-nyl)amino)-1,2,3,4,4a,4b,5,6,7,9,10,10a-dodecahydrophenanthrene-1-carboxylate (13). Rf = 0.62 (CHCl3); 1H NMR (600 MHz, CDCl3): δ = 0.61 (t, J = 7.5 Hz, 3 H, СН3-16), 0.83 (s, 3 Н, СH3-20), 0.85 (s, 3 H, СН3-17), 1.13-1.22 (m, 3 Н, CH2-15, H-1), 1.20 (s, 3 H,

122

1133 14

1155

СН3-19), 1.28 (m, 2 Н, CН2-12), 1.38-1.45 (m, 1 Н, Н-6), 1.49 (m, 1 Н, Н-11), 1.52-1.67 (m, 3 Н, СH2-2, H-6), 1.61 (m, 1 Н, Н-3), 1.67 (m, 1 Н, Н-11), 1.74 (m, 2 Н, Н-1,3),

116

H 88

5

H

6

77

NH 1''

22''

Mee CO22M C 18

1122, 1132, 1145, 1190, 1215, 1247, 1348, 1384, 1433, 1446, 1460, 1485, 1529, 1581, 1622, 1724, 2852, 2868, 2931, 2947, 3402 cm –1. UV (EtOH) λmax nm (lgε): 191 (3.36), 196 (3.61), 248 (4.02). MS (EI): m/z (%) = 454 (11), 317 (40), 257 (100), 121 (30), 55 (58), 43 (42), 41 (82), 29 (54), 15 (25); calcd. for C27H38O4N2: 454.2826, found

'

4'

1177 20

C NMR (101 MHz, CDCl3): see Table S1. IR (neat): ν = 734, 758, 825, 1060, 1080, 1095,

13

1133

'

6'

5''

1.90 (m, 1 Н, Н -9), 2.07 (dd, J = 12.4, 2.4 Hz, 1 Н, Н-5), 3.64 (s, 3 Н, ОСН3), 3.75 (ddd, J = 12.0, 5.6, 2.3 Hz, 1 Н, Н-7), 4.03 (d, J = 5.6 Hz, 1 Н, NH), 5.34 (s, 1 Н, Н-14), NO22 N 33'

'

6.78 (dd, J = 8.1, 2.1 Hz, 1 Н, Н-6’), 7.21 (t, J = 8.1 Hz, 1 Н, Н-5’), 7.29 (t, J = 2.1 Hz, 1 Н, Н-2’), 7.44 (dd, J = 8.1, 2.1 Hz, 1 Н, Н-4’). 13C NMR (151 MHz, CDCl3): see Table

4''

S1. IR (neat): ν˜ = 723, 741, 822, 1047, 1060, 1099, 1132, 1146, 1184, 1244, 1280, 1350, 1385, 1460, 1531, 1539, 1620, 1726, 2853, 2866, 2928, 2949, 3399 cm –1. UV (EtOH) λmax nm (lgε): 246 (4.3), 405 (3.1). MS (EI): m/z (%) = 454 (3), 425 (15), 329 (13), 318 (16), 317 (73), 287 (13), 286 (66), 285 (22), 269 (14), 258 (23), 257 (100),

6

207 (10), 181 (9), 173 (11), 149 (8), 147 (9), 145 (10), 121 (25), 119 (8), 109 (8), 105 (10), 95 (13), 93 (8), 91 (9), 81 (11), 55 (7), 41 (5); calcd. for C27H38O4N2: 454.2826, found 454.2820.

(1R,4aR,4bR,7S,8S,10aR)-Methyl 7-ethyl-1,4a,7-trimethyl-8-((3-nitrophenyl)amino)-1,2,3,4, 4a,4b,5,6,7,8,10,10a-dodecahydrophenanthrene-1-carboxylate (15). Rf = 0.62 (CHCl3); [α]D = - 138.55 (c 0.2, СНCl3); 1H NMR (600 MHz, CDCl3): δ = 0.77 (t, J = 7.4 Hz, 3 H, СН3-16), 0.86 (s, 3 H, СН3-17), 0.88 (s, 3 Н, СH3-20), 1.07 (m, 1 Н,

117 12 111 13 99 114

220 2

11

3

10

Н-1), 1.21 (s, 3 H, СН3-19), 1.24-1.32 (m, 2 Н, H-15), 1.35-1.44 (m, 4 Н, CH2-12, H-11,2), 1.48-1.65 (m, 6 Н, CH2-6,3, H-2,11), 1.70 (dd, J = 12.0, 3.0 Hz, 1Н, H-5), 1.81 (m,

16

NH

H 8 H

5

4

15

Jgem= 13.2 Hz, 1 Н, Н-1), 1.88 (m, 1 Н, Н-9), 3.48 (brd, 1 Н, J = 5.6 Hz, Н-14), 3.51 (s, 3 Н, ОСН3), 4.09 (brd, 1 H, J = 5.6 Hz, NH), 5.59 (d, J = 6.0 Hz, 1 Н, Н-7), 6.85 (dd, J '

1''

22'

NO2

7

66

H e Me CO2M

'

3'

' 6'

1155

13

C NMR (151 MHz, CDCl3): see Table S2. IR

(neat): ν˜ = 671, 735, 758, 826, 1103, 1121, 1146, 1190, 1215, 1250, 1348, 1385, 1433, 1460, 1477, 1528, 1582, 1622, 1713, 2855, 2870, 2878, 2930, 2949, 3408 cm–1. UV

4''

55''

= 8.2, 1.9 Hz, 1 Н, Н-6’), 7.21 (t, J = 8.2 Hz, 1 Н, Н-5’), 7.42 (t, J = 1.9 Hz, 1 Н, Н-2’), 7.44 (dd, J = 8.2, 1.9 Hz, 1 Н, Н-4’).

(EtOH) λmax nm (lgε): 250 (4.5), 408 (3.2). MS (EI): m/z (%) = 454 (4), 440 (1), 437 (6), 318 (5), 317 (21), 287 (6), 285 (4), 258 (19), 257 (100), 256 (4), 201 (8), 199 (5), 173

(6), 161 (4), 145 (5), 121 (13), 119 (6), 105 (6), 93 (5), 91 (5), 85 (9), 83 (16), 55 (7), 47 (5), 41 (4); calcd. for C27H38O4N2: 454.2826, found 454.2818.

(1R,4aR,4bR,7S,9R,10aR)-Methyl 7-ethyl-9-hydroxy-1,4a,7-trimethyl-1,2,3,4,4a,4b,5,6,7,9, 10,10a-dodecahydrophenanthrene-1-carboxylate (14). mp 60-62оС. [α]D = + 94.4 (c 1.1, СНCl3). HRMS calcd. for C21H34O3: 334.2502, found 334.2496. The 1H NMR and 13C NMR spectra agreed with those published9. (1R,4aR,4bR,7S,9R,10aR)-Methyl 9-((2-bromophenyl)amino)-7-ethyl-1,4a,7-trimethyl-1,2,3,4,4a,4b,5,6,7,9,10,10a-dodecahydrophenanthrene-1-carboxylate (22). Rf = 0.66 (CHCl3); [α]D = + 1.96 (c 0.5, СНCl3); 1H NMR (400 MHz, CDCl3): δ = 0.73 (t, J = 7.5 Hz, 3 H, СН3-16), 0.86 (s, 3 Н, СH3-20), 0.90 (s, 3 H, СН3-17), 1.17 (m, 2 Н, Н1177

1111 99

2200

2 33

11

1100 55

1133 1144

188

Н-14), 6.48 (dt, J = 7.5, 1.8 Hz, 1 Н, Н-4’), 6.67 (dd, J =7.5, 1.8 Hz, 1 Н, Н-6’), 7.09 (dt, J =7.5, 1.6 Hz, 1 Н, Н-5’), 7.38 (dd, J =7.5, 1.6 Hz, 1 Н, Н-3’).

Brr

7

66

H O2Mee CO

119

Н, Н-6), 1.78 (m, 2 Н, Н-3,1), 2.08 (m, 1 Н, Н-9), 2.34 (dd, J = 12.4, 2.0 Hz, 1 Н, Н-5), 3.42 (s, 3 Н, ОСН3), 3.95 (dd, J = 3.8, 1.5 Hz, 1 Н, Н-7), 4.05 (brs, 1 Н, NH), 5.53 (s, 1 Н,

116

1155

8

H

44

1,12), 1.21 (s, 3 H, СН3-19), 1.20 (m, 2 Н, CH2-15), 1.29 (m, 1 Н, H-12), 1.42 (m, 1 Н, Н-6), 1.50, 1.53, 1.58, 1.60 (all m, 5 Н, CH2-2,11, H-3), 1.73 (ddd, J = 13.6, 12.4, 3.8 Hz, 1

1122

HN

22'

'

33'

2222

'

'

6'

C NMR (101 MHz,

CDCl3): see Table S2. IR (neat): ν˜ = 740, 1018, 1064, 1120, 1145, 1157, 1190, 1244, 1282, 1315, 1384, 1431, 1446, 1460, 1508, 1595, 1616, 1726, 2850, 2868, 2947, 3381

'

'

1'

13

cm–1. UV (EtOH) λmax nm (lgε): 241 (4.05), 475 (3.46). MS (EI): m/z (%) = 487 (24), 287 (42), 257 (91), 173 (97), 171 (100), 121 (22), 92 (38), 65 (43), 47 (33), 35 (14); calcd. for

44'

'

55'

C27H38O2NBr: 487.2080, found 487.2076.

(1R,4aR,4bR,7S,9R,10aR)-Methyl 9-(2-amino-3-bromophenyl)-7-ethyl-1,4a,7-trimethyl-1,2,3,4,4a,4b,5,6,7,9,10,10a-dodecahydrophenanthrene-1-carboxylate (28). Rf = 0.68 (CHCl3); [α]D = - 15.89 (c 0.2, СНCl3); 1H NMR (400 MHz, CDCl3): δ = 0.71 (t, J = 7.5 Hz, 3 H, СН3-16), 0.88 (m, 1 Н, Н-1), 0.89 (s, 3 Н, СH3-20), 0.93 (s, 3 H, СН317), 1.16 (s, 3 H, СН3-19), 1.21-1.26 (m, 2 Н, CH2-15), 1.38-1.56 (m, 8 Н, CH2-12,2,11, H-3,6), 1.61 (m, 2 Н, Н-3,1), 1.70 (m, 1 Н, Н-5), 1.80 (m, 1 Н, Н-9), 2.22 (m, 1 Н, Н-6), 3.15

177

1111

2200

2 33

1199

11

1122

9

1100 55

44

66

155

NH2 H N ' 22'

H 8

H CO22Mee 188

1133 1144

1''

7

1166

Brr B '

33'

'

'

66'

28

44'

'

5'

7

(s, 3 Н, ОСН3), 3.53 (d, J = 4.8 Hz, 1 Н, Н-7), 4.08 (brs, 2 Н, NH2), 5.35 (s, 1 Н, Н-14), 6.57 (t, J = 7.8 Hz, 1 Н, Н-5’), 7.06 (dd, J = 7.8, 1.6 Hz, 1 Н, Н-6’), 7.24 (dd, J = 7.8, 1.6 Hz, 1 Н, Н-4’). 13C NMR (101 MHz, CDCl3): see Table S3. IR (neat): ν˜ = 754, 1150, 1169, 1192, 1261, 1450, 1462, 1585, 1612, 1720, 2849, 2868, 2936, 2963, 3410, 3493 cm –1. UV (EtOH) λmax nm (lgε): 207 (4.53), 241 (3.81), 293 (3.46). MS (EI): m/z (%) = 487 (6), 474 (12), 472 (14), 430 (16), 429 (25), 428 (16), 427 (23), 412 (30), 414 (28), 398 (9), 358 (10), 306 (12), 287 (17), 257 (10), 242 (20), 241 (100), 227 (15), 197 (8), 196 (8), 186 (9), 184 (9), 182 (11), 121 (8), 71 (21), 59 (8), 55 (10), 41 (6); calcd. for C27H38O2NBr: 487.2080, found 487.2076.

(1R,4aR,4bR,7S,9S,10aR)-Methyl 9-(4-amino-3-bromophenyl)-7-ethyl-1,4a,7-trimethyl-1,2,3,4,4a,4b,5,6,7,9,10,10a-dodecahydrophenanthrene-1-carboxylate (29). Rf = 0.68 (CHCl3); [α]D = - 37.89 (c 0.3, СНCl3); 1H NMR (400 MHz, CDCl3): δ = 0.85 (t, J = 7.5 Hz, 3 H, СН3-16), 0.88 (s, 3 Н, СH3-20), 0.94 (s, 3 H, СН3-17), 1.03 (m, 1 Н, Н-1), 1177 13 1144

99 11 22

3

100

H

55

4

66

H O2Mee CO

19

188

1.20 (s, 3 H, СН3-19), 1.32 (q, J = 7.5 Hz, 2 Н, CH2-15), 1.36 (m, 2 Н, CH2-12), 1.49 (m, 3 Н, H-2,11,3), 1.60 (m, 3 Н, H-2,11,6), 1.69 (m, 2 Н, Н-3,1), 1.79 (dd, J = 12.2, 2.4 Hz, 1

12

1111

2200

8

H H

7

11'

'

Н, Н-5), 1.87 (m, 2 Н, Н-6,9), 3.39 (d, J = 4.8 Hz, 1 Н, Н-7), 3.56 (s, 3 Н, ОСН3), 5.38 (s, 1 Н, Н-14), 6.65 (d, J = 8.6 Hz, 1 Н, Н-5’), 6.95 (d, J = 8.6 Hz, 1 Н, Н-6’), 7.29 (s, 1 Н, Н-

1166

1155

'

22'

'

2’). 13C NMR (101 MHz, CDCl3): see Table S3. IR (neat): ν˜ = 756, 816, 1142, 1163, 1173, 1190, 1250, 1308, 1385, 1435, 1460, 1503, 1620, 1722, 2851, 2870, 2945, 3373 cm –

Brr

. UV (EtOH) λmax nm (lgε): 206 (3.23), 242 (3.93), 298 (4.43). MS (EI): m/z (%) = 487 (3), 460 (37), 458 (36), 321 (42), 319 (43), 287 (55), 241 (33), 227 (52), 225 (40), 197

1

33'

' 6'

'

'

29

(40), 186 (100), 184 (100), 182 (31), 181 (31), 159 (33), 157 (37), 146 (45), 145 (36), 121 (45), 105 (30), 95 (46), 81 (33), 55 (30), 41 (30); calcd. for C27H38O2NBr: 487.2080,

NH22

44'

55'

found 487.2084

(1R,4aR,4bR,7S,8S,10aR)-Methyl 8-((2-bromophenyl)amino)-7-ethyl-1,4a,7-trimethyl-1,2,3,4,4a,4b,5,6,7,8,10,10a-dodecahydrophenanthrene-1-carboxylate (30). Rf = 0.68 (CHCl3); 1H NMR (400 MHz, CDCl3): δ = 0.76 (t, J = 7.5 Hz, 3 H, СН3-16), 0.85 (s, 3 H, СН3-17), 0.87 (s, 3 Н, СH3-20), 1.10 (m, 1 Н, Н-1), 1.22 (s, 3 H, СН3-19),

17 17

12 11 13 11 14 99 14

20 20 2 3

11

10

66

H Me CO2Me

1.22-1.35 (m, 2 Н, H-15), 1.39-1.43 (m, 4 Н, CH2-12, H-11,2), 1.47-1.61 (m, 6 Н, CH2-6,3, H-2,11), 1.68 (dd, J = 12.1, 3.0 Hz, 1Н, H-5), 1.81 (m, Jgem = 13.0 Hz, 1 Н, Н-1),

16

1.90 (m, 1 Н, Н-9), 3.45 (brs, 1 Н, Н-14), 3.54 (s, 3 Н, ОСН3), 5.50 (brd, J = 5.9 Hz, 1 Н, Н-7), 6.49 (dt, J = 8.1, 1.6 Hz, 1 Н, Н-4’), 6.71 (d, J =8.1, 1 Н, Н-6’), 7.09 (dt, J =8.1,

NH 1'

H 8 H

5

4

15

1'

2' 2'

1.6 Hz, 1 Н, Н-5’), 7.38 (dd, J =8.1, 1.6 Hz, 1 Н, Н-3’).

Br Br

7 3'

6'

30

1321, 1384, 1431, 1462, 1510, 1595, 1695, 1726, 2850, 2868, 2925, 3417 cm–1. UV (EtOH) λmax nm (lgε): 249 (3.76), 301 (3.10). MS (EI): m/z (%) = 487 (21), 317 (57), 287

4' 4'

5' 5'

C NMR (101 MHz, CDCl3): see Table S3. IR (neat): ν˜ = 738, 1016, 1062, 1105, 1120, 1145, 1188, 1244, 1280,

13

(21), 257 (100), 207 (19), 201 (19), 173 (10), 147 (12), 133 (10), 105 (12), 41 (5); calcd. for C27H38O2NBr: 487.2080, found 487.2068.

(1R,4aR,4bR,7S,9S,10aR)-Methyl 9-((2-bromophenyl)amino)-7-ethyl-1,4a,7-trimethyl-1,2,3,4,4a,4b,5,6,7,9,10,10a-dodecahydrophenanthrene-1-carboxylate (31). Rf = 0.68 (CHCl3); 1H NMR (400 MHz, CDCl3): δ = 0.79 (s, 3 Н, СH3-20), 0.82 (t, J = 7.5 Hz, 3 H, СН3-16), 0.89 (s, 3 H, СН3-17), 1.17 (s, 3 H, СН3-19), 1.20 (m, 1 Н, Н-1),

17 17

22 3

11

44

20 20

11 11 99

10 10

H 88 H

55

12 12

CO2Me 18 18

Br

4.9, 3.0 Hz,1 Н, Н-7), 3.65 (s, 3 Н, ОСН3), 4.07 (brd, J = 4.9 Hz, 1 Н, NH), 5.36 (s, 1 Н, Н-14), 6.61 (dt, J = 8.4, 1.8 Hz, 1 Н, Н-4’), 6.76 (dd, J = 8.4, 1.8 Hz, 1 Н, Н-6’),

2''

N H

31

7.09 (dt, J = 8.4, 1.5 Hz, 1 Н, Н-5’), 7.39 (dd, J = 8.4, 1.5 Hz, 1 Н, Н-3’).

3'

11''

7 66 7

H 19 19

1.24-1.29 (m, 3 Н, CH2-15, Н-12), 1.34 (m, 1 Н, Н-12), 1.41-1.83 (m, 9 Н, CH2-6,2,11,3, H-1), 2.01 (m, 1 Н, Н-9), 2.35 (dd, J = 12.2, 2.8 Hz, 1 Н, Н-5), 3.55 (ddd, J = 12.2,

16 16

15 15

13 13 14 14

C NMR (101 MHz, CDCl3): see Table S3. IR (neat): ν˜ = 756, 816, 1142, 1163, 1173, 1190,

13

44' 66'' 55'

8

1250, 1308, 1385, 1435, 1460, 1503, 1620, 1722, 2851, 2870, 2945, 3373 cm–1. UV (EtOH) λmax nm (lgε): 206 (3.23), 242 (3.93), 298 (4.43). MS (EI): m/z (%) = 487 (23), 362 (40), 317 (26), 287 (63), 257 (76), 241 (31), 227 (43), 194 (100), 166 (75), 161 (57), 145 (23), 121 (41), 109 (26), 107 (26), 105 (29), 95 (36), 93 (29), 91 (23), 81 (30), 55 (31), 41 (23); calcd. for C27H38O2NBr: 487.2080, found 487.2083. (1R,4aR,4bR,7S,9R,10aR)-Methyl

9-((2-chloro-4-nitrophenyl)amino)-7-ethyl-1,4a,7-trimethyl-1,2,3,4,4a,4b,5,6,7,9,10,10a-dodecahydrophenan-threne-1-

carboxylate (23). 17 11 9

20 2 33

1

10 10

13 13 14

15 15

(both m, 2 Н, Н-1,12), 1.22 (s, 3 H, СН3-19), 1.23 (m, 2 Н, H-15), 1.30 (m, 1 Н, H-12), 1.43 (dd, J = 12.4, 2.2 Hz, 1 Н, Н-6), 1.57-1.62 (m, 5 Н, CH2-2,11, H-3), 1.66 (m, 1 Н,

Cl

77

6

Rf = 0.66 (CHCl3); [α]D = + 95,33 (c 0.3, CHCl3); 1H NMR (400 MHz, CDCl3): δ = 0.77 (t, J = 7.5 Hz, 3 H, СН3-16), 0.87 (s, 3 Н, СH3-20), 0.92 (s, 3 H, СН3-17), 1.15, 1.18

16

H 8

5

44

12 12

Н-3), 1.74 (m, Jgem = 12.9 Hz, 1 Н, Н-1), 1.86 (ddd, J = 13.6, 12.4, 2.6 Hz, 1 Н, Н-6), 2.00 (dd, J = 8.5, 1.8 Hz, 1 Н, Н-9), 2.31 (dd, J = 12.4, 2.2 Hz, 1 Н, Н-5), 3.52 (s, 3 Н,

2' 2'

NH 1'1'

H H

ОСН3), 4.04 (dd, J = 5.2, 2.6 Hz, 1 Н, Н-7), 5.58 (d, J = 5.2 Hz, 1 Н, NH), 5.63 (s, 1 Н, Н-14), 6.70 (d, J = 9.1 Hz, 1 Н, Н-6’), 8.00 (dd, J = 9.1, 2.7 Hz, 1 Н, Н-5’), 8.19 (d, J

3'

CO2Me CO

19 19

18

6'6'

23 23

= 2.7 Hz, 1 Н, Н-3’). 13C NMR (101 MHz, CDCl3): see Table S2. IR (neat): ν˜ = 746, 894, 1062, 1122, 1139, 1245, 1282, 1325, 1448, 1458, 1500, 1527, 1589, 1720, 2852,

NO22 4'4' NO

5'

2868, 2949, 3402 cm–1. UV (EtOH) λmax nm (lgε): 373 (4.84). MS (EI): m/z (%) = 488 (5), 318 (11), 317 (45), 258 (22), 257 (100), 121 (26), 105 (11), 81 (8), 55 (11), 41 (8);

calcd. for C27H37O4N2Cl: 488.2436, found 488.2433. (1R,4aR,4bR,7S,9R,10aR)-Methyl 7-ethyl-9-((4-methoxy-2-nitrophenyl)-amino)-1,4a,7-trimethyl-1,2,3,4,4a,4b,5,6,7,9,10,10a-dodecahydrophenan-threne-1-carboxylate (24). M.p. 174-176˚С (MeOH); Rf = 0.63 (CHCl3); [α]D = - 213,33 (c 0.1, CHCl3); 1H NMR (400 MHz, CDCl3): δ = 0.73 (t, J = 7.5 Hz, 3 H, СН3-16), 0.86 (s, 3 Н, СH3-20),

17 12 12 13 11 11 13 9 14

20 2 33

1

10 10

15 15

6

7

H H

5 Н, CH2-2,11, Н-3), 1.72 (m, 1 Н, Н-3), 1.75 (m, 1 Н, Н-1), 1.81 (ddd, J = 13.4, 12.2, 3.0 Hz, 1 Н, Н-6), 2.06 (dd, J = 8.5, 1.6 Hz, 1 Н, На-9), 2.34 (dd, J = 12.2, 2.2

16 16

H 8

5

44

0.91 (s, 3 H, СН3-17), 1.12-1.19 (m, 2 H, H-1,12), 1.20 (s, 3 H, СН3-19), 1.23 (m, 2 Н, CH2-15), 1.30 (m, 1 Н, H-12), 1.43 (m, Jgem = 13.4 Hz, 1 H, Н-6), 1.47-1.62 (m, Hz, 1 Н, Н-5), 3.43 (s, 3Н, ОСН3), 3.77 (s, 3H, C-4’-OCH3), 4.14 (dd, J = 6.0, 3.0 Hz, 1 Н, Н-7), 5.57 (s, 1 Н, Н-14), 6.89 (d, J = 9.1 Hz, 1 Н, Н-6’), 7.07 (dd, J = 9.1,

NO2 NH 1'1'

2.6 Hz, 1 Н, Н-5’), 7.58 (d, J = 2.6 Hz, 1 Н, Н-3’), 8.48 (d, J = 6.0 Hz, 1 Н, NH).

2'

3'

18 18

6'6'

24 24

5' 5'

C NMR (101 MHz, CDCl3): see Table S2. IR (neat): ν˜ = 759, 931, 1041, 1049,

1062, 1141, 1190, 1240, 1284, 1344, 1411, 1444, 1460, 1517, 1571, 1726, 2850, 2868, 2949, 3352 cm –1. UV (EtOH) λmax nm (lgε): 241 (4.05), 475 (3.46). MS (EI):

CO2Me

19

13

OMe 4'4' OMe

m/z (%) = 484 (28), 317 (24), 287 (36), 258 (21), 257 (100), 227 (11), 168 (18), 121 (24), 41 (3); calcd. for C27H40O5N2: 484.2932, found 484.2930.

(1R,4aR,4bR,7S,9R,10aR)-Methyl 7-ethyl-1,4a,7-trimethyl-9-((3-(trifluoromethyl)phenyl)amino)-1,2,3,4,4a,4b,5,6,7,9,10,10a-dodecahydro-phenanthrene-1-carboxylate (25). Rf = 0.49 (CHCl3); [α]D = + 3.2 (c 0.2, СНCl3); 1H NMR (400 MHz, CDCl3): δ = 0.74 (t, J = 7.5 Hz, 3 H, СН3-16), 0.86 (s, 3 Н, СH3-20), 0.90 (s, 3 H, СН3-17), 1.15 (m, 2 Н, 17 17

22 3

19

1 44

11 9

10 10

H 88

5

6

77

H H CO22Me CO 18 18

Н-1,12), 1.21 (s, 3 H, СН3-19), 1.31 (m, 2 Н, CH2-15), 1.41 (m, 1 Н, H-12), 1.44 (m, 1 Н, Н-6), 1.55 (m, 2 Н, CН2-2), 1.60-1.64 (m, 3 Н, CH2-11, H-3), 1.73 (m, 2 Н, Н-1,3),

12

20

25 25

13 13 14

15

NH 1'1'

1.76 (m, 1 Н, Н-6), 2.05 (dd, J = 8.7, 1.8 Hz, 1 Н, Н-9), 2.28 (dd, J = 12.2, 2.2 Hz, 1 Н, Н-5), 3.39 (s, 3 Н, ОСН3), 3.91 (brd, 1 Н, Н-7), 4.17 (brs, 1 H, NH), 5.57 (s, 1 Н, Н-

16 16

14), 6.73 (d, J = 7.5 Hz, 1 Н, Н-6’), 6.83 (s, 1 Н, Н-2’), 6.84 (d, J = 7.5 Hz, 1 Н, Н-4’), 7.19 (t, J = 7.5 Hz, 1 Н, Н-5’). 13C NMR (101 MHz, CDCl3): see Table S2. IR (neat): ν˜ 2'2'

CF3

= 698, 758, 781, 860, 871, 993, 1066, 1122, 1163, 1244, 1346, 1438, 1479, 1492, 1614, 1716, 2852, 2870, 2949, 3404 cm –1. UV (EtOH) λmax nm (lgε): 259 (3.95), 312

3' 6' 6'

4' 4' 5'

9

(3.13). MS (EI): m/z (%) = 477 (22), 454 (11), 317 (28), 258 (18), 257 (100), 256 (4), 227 (7), 161 (6), 121 (18), 105 (8), 55 (8), 41 (6); calcd. for C28H38O2NF3: 477.2849, found 477.2842.

(1R,4aR,4bR,7S,8S,10aR)-Methyl 7-ethyl-1,4a,7-trimethyl-8-((3-(trifluoromethyl)phenyl)-amino)-1,2,3,4,4a,4b,5,6,7,8,10,10a-dodecahydrophenanthrene-1-carboxylate (32). Rf = 0.49 (CH3Cl); 1H NMR (400 MHz, CDCl3): δ = 0.78 (t, J = 7.5 Hz, 3 H, СН3-16), 0.85 (s, 3 H, СН3-17), 0.87 (s, 3 Н, СH3-20), 1.06 (m, 1 Н, Н-1), 1.21 (s, 3 H, СН3-

17 11 9

20

11

2 33

10 10

13 13 14

H 8

5

44

19), 1.32-1.36 (m, 2 Н, H-15), 1.41 (m, 4 Н, CH2-12, H-11,2), 1.47-1.55 (m, 6 Н, CH2-6,3, H-2,11), 1.64 (dd, J = 11.8, 2.8 Hz, 1Н, H-5), 1.81 (m, Jgem = 13.2 Hz, 1 Н, Н-

12 12

15 15

2'

H H

6.85 (d, J = 8.1 Hz, 1 Н, Н-4’), 7.19 (t, J = 8.1 Hz, 1 Н, Н-5’).

C NMR (101 MHz, CDCl3): see Table S3. IR (neat): ν˜ = 698, 758, 783, 993, 1066, 1122, 1163, 1247,

13

1280, 1319, 1344, 1384, 1435, 1444, 1460, 1481, 1492, 1519, 1614, 1714, 1724, 2854, 2871, 2929, 3404 cm –1. UV (EtOH) λmax nm (lgε): 257 (4.18), 312 (3.38). MS

6'6'

18

CF33

3'

7 6 7

CO2Me CO

19 19

1'1'

HN

1), 1.88 (m, 1 Н, Н-9), 3.43 (brs, 1 Н, Нb-14), 3.51 (s, 3 Н, ОСН3), 3.91 (brs, 1 H, NH), 5.52 (d, J = 5.4 Hz, 1 Н, Н-7), 6.73 (d, J = 8.1 Hz, 1 Н, Н-6’), 6.80 (s, 1 Н, Н-2’),

16

4'4'

5'

32

(EI): m/z (%) = 477 (8), 317 (58), 287 (20), 257 (100), 227 (10), 173 (12), 161 (9), 145 (12), 121 (23), 105 (10), 93 (9), 41 (5); calcd. for C28H38O2NF3: 477.2849, found 477.2842.

(1R,4aR,4bR,7S,9S,10aR)-Methyl 7-ethyl-1,4a,7-trimethyl-9-((3-(trifluoromethyl)phenyl)-amino)-1,2,3,4,4a,4b,5,6,7,9,10,10a-dodecahydrophenanthrene-1-carboxylate (33). Rf = 0.49 (CHCl3); [α]D = - 34.1 (c 0,2, СНCl3); 1H NMR (400 MHz, CDCl3): δ = 0.64 (t, J = 7.5 Hz, 3 H, СН3-16), 0.84 (s, 3 Н, СH3-20), 0.86 (s, 3 H, СН3-17), 1.11-1.17 (m, 3

17 17

H, CH2-15, H-1), 1.20 (s, 3 H, СН3-19), 1.24-1.32 (m, 2 Н, CН2-12), 1.39 (m, Jgem = 13.0 Hz, 1 Н, Н-6), 1.49-1.59 (m, 4 Н, CH2-2, Н-11,6), 1.62 (m, 1 Н, Н-3), 1.67 (m, 1 Н,

12

12 11 13 11 14 99 14

20 20

22 3

11 4

10

15

Н-11), 1.70-1.78 (m, 2 Н, Н-1,3), 1.90 (dd, J = 8.4, 1.8 Hz, 1 Н, Н-9), 2.07 (dd, J = 12.4, 2.7 Hz, 1 Н, Н-5), 3.64 (s, 3 Н, ОСН3), 3.70 (ddd, J = 12.0, 4.8, 2.8 Hz, 1 H, Н-7),

16 16

3.89 (m, 1 H, NH), 5.38 (s, 1 Н, Н-14), 6.66 (d, J = 8.1 Hz, 1 Н, Н-6’), 6.69 (s, 1 Н, Н-2’), 6.85 (d, J = 8.1 Hz, 1 Н, Н-4’), 7.19 (t, J = 8.1 Hz, 1 Н, Н-5’).

H 8 H

5

66

7

NH 1' 2'2'

H H

3'

Me CO 2Me

19

18

6'

33

13

C NMR (101 MHz,

CDCl3): see Table S3 (Supp. Info). IR (neat): ν˜ = 698, 756, 783, 858, 871, 993, 1068, 1122, 1163, 1244, 1344, 1444, 1517, 1614, 1718, 2852, 2870, 2933, 3398 cm–1. UV

CF3

(EtOH) λmax nm (lgε): 256 (3.92), 312 (3.13). MS (EI): m/z (%) = 477 (38) [M]+, 475 (11), 317 (28), 287 (20), 258 (20), 257 (100), 255 (10), 173 (14), 161 (15), 121 (32), 105

4'4' 5'5'

(20), 55 (19), 41 (15); calcd. for C28H38O2NF3: 477.2849, found 477.2843.

(1R,4aR,4bR,7S,9R,10aR)-Methyl 7-ethyl-1,4a,7-trimethyl-9-((4-(trifluoromethyl)phenyl)-amino)-1,2,3,4,4a,4b,5,6,7,9,10,10a-dodeca-hydrophenanthrene-1-carboxylate (26). Rf = 0.63 (CHCl3); [α]D = + 22.98 (c 0.7, СНCl3); 1H NMR (400 MHz, CDCl3): δ = 0.75 (t, J = 7.5 Hz, 3 H, СН3-16), 0.85 (s, 3 Н, СH3-20), 0.91 (s, 3 H, СН3-17), 1.15 17 17

22 3

19

11 4

11 11 99

10

H 88

5

6

13 13 14

15

77

Н-6), 2.02 (dd, J = 8.6, 1.8 Hz, 1 Н, Н-9), 2.24 (dd, J = 12.0, 1.8 Hz, 1 Н, Н-5), 3.37 (s, 3 Н, ОСН3), 3.62 (d, 1 Н, J = 5.2, NН), 3.92 (brd, 1 Н, J = 5.2, Н-7), 5.56 (s, 1

16 16

NH 1'1'

H H CO22Me 18 18

(m, 2 Н, Н-1,12), 1.20 (s, 3 H, СН3-19), 1.30 (m, 2 Н, CH2-15), 1.40 (m, 1 Н, H-12), 1.43 (m, 1 Н, Н-6), 1.50-1.63 (m, 6 Н, CH2-2,11,3), 1.71 (m, 1 Н, Н-1), 1.73 (m, 1 Н,

12

20 20

Н, Н-14), 6.60 (d, J = 8.5 Hz, 2 Н, Н-2’,6’), 7.33 (d, J = 8.5 Hz, 2 Н, Н-3’,5’).

C NMR (101 MHz, CDCl3): see Table S2. IR (neat): ν˜ = 758, 823, 1060, 1082, 1110,

13

1159, 1186, 1242, 1251, 1325, 1365, 1435, 1446, 1460, 1531, 1616, 1716, 2852, 2870, 2947, 3400 cm–1. UV (EtOH) λmax nm (lgε): 264 (3.97), 394 (3.06). MS (EI): m/z

2' 3'

26

4' 4'

6' 6'

5'

CF 3

10

(%) = 477 (7), 317 (28), 258 (20), 257 (100), 161 (23), 145 (19), 123 (18), 121 (46), 107 (28), 93 (29), 91 (32), 81 (15), 59 (19), 55 (54), 57 (35), 43 (47), 41 (54), 39 (17); calcd. for C28H38O2NF3: 477.2849, found 477.2845.

(1R,4aR,4bR,7S,8S,10aR)-Methyl 7-ethyl-1,4a,7-trimethyl-8-((4-(trifluoromethyl)phenyl)-amino)-1,2,3,4,4a,4b,5,6,7,8,10,10a-dodeca-hydrophenanthrene-1-carboxylate (34). Rf = 0.63 (CHCl3). 1H and

17 17

12 11 11 13 14 99 14

20 20

2 3

11

10

4

16

11 Н, CH2-12,6,3,11,2, H-5), 1.80 (m, 1 Н, Н-1), 1.92 (m, 1 Н, Нa-9), 3.53 (s, 3 Н, ОСН3), 3.49 (brd, 3.56 (brd, 1 H, J = 5.8 Hz, H-14), 3.77 (d, 1 H, 3.56 (brd, 1 H, J = 5.8

NH 1'

1'

Hz, NH), 5.55 (d, J = 5.9 Hz, 1 Н, Н-7), 6.60 (d, J = 8.5 Hz, 2 Н, Н-2’,6’), 7.34 (d, J = 8.5 Hz, 2 Н, Н-3’,5’). 13C NMR (101 MHz, CDCl3): see Table S3.

2' 2'

7 66

H Me CO2Me

C NMR data of compound 34 was obtained from the spectra of a mixture of compounds 26, 34, 35 (in a ratio 2.8:1.4:1). 1H NMR (400 MHz,

CDCl3): δ = 0.76 (t, J = 7.5 Hz, 3 H, СН3-16), 0.85 (s, 3 Н, СH3-17), 0.88 (s, 3 H, СН3-20), 1.07 (m, 1 Н, Н-1), 1.22 (s, 3 H, СН3-19), 1.21 (m, 2 H, CН2-15), 1.39-1.76 (m,

15

H 8 H

5

13

3'

6'

4'

34

CF33

5' 5'

(1R,4aR,4bR,7S,9S,10aR)-Methyl 7-ethyl-1,4a,7-trimethyl-9-((4-(trifluoro-methyl)phenyl)-amino)-1,2,3,4,4a,4b,5,6,7,9,10,10a-dodecahydro-phenanthrene-1-carboxylate (35). Rf = 0.63 (CHCl)3; [α]D = - 61.67 (c 0.1, СНCl3); 1H NMR (400 MHz, CDCl3): δ = 0.65 (t, J = 7.5 Hz, 3 H, СН3-16), 0.83 (s, 3 Н, СH3-20), 0.86 (s, 3 H, СН3-17), 1.16 (m, 2 Н,

17

2 3

1

10 10

44

19

Н-1,12), 1.20 (s, 3 H, СН3-19), 1.24 (m, 2 Н, CH2-15), 1.34-1.40 (m, 1 Н, H-12), 1.56-1.60 (m, 5 Н, CH2-2,11, H-6), 1.62-1.81 (m, 4 H, CH2-3, Н-6,1), 1.88 (dd, J = 9.0, 2.1

12 12 13 11 14 9 14

20

Hz, 1 Н, Н-9), 2.05 (dd, J = 12.4, 2.1 Hz, 1 Н, Н-5), 3.64 (s, 3 Н, ОСН3), 3.72 (ddd, J = 12.0, 6.0, 2.8 Hz, 1 Н, Н-7), 3.95 (m, 1 H, NH), 5.36 (s, 1 Н, Н-14), 6.51 (d, J = 8.6

16

15

Hz, 2 Н, Н-2’,6’), 7.33 (d, J = 8.6 Hz 2 Н, Н-3’,5’).

H 8

55

6

7

H CO2Me

HN HN

3'

317 (25), 309 (17), 257 (100), 174 (15), 121 (30), 93 (18), 91 (18), 85 (25), 83 (44), 56 (21), 55 (32), 43 (17), 41 (27), 29 (13); calcd. for C28H38O2NF3: 477.2849, found

18

35 35

C NMR (101 MHz, CDCl3): see Table S3. IR (neat): ν˜ = 642, 657, 829, 1064, 1106, 1159, 1186, 1241, 1261, 1321,

1365, 1434, 1450, 1461, 1535, 1616, 1712, 2850, 2929, 2946, 3398, 3415 cm–1. UV (EtOH) λmax nm (lgε): 221 (3.48), 322 (3.93), 350 (3.10). MS (EI): m/z (%) = 477 (40),

2'

1' 1'

13

6'

4'

5'

CF 3

477.2853.

(1R,4aR,4bR,7S,9R,10aR)-Methyl 9-((4-acetylphenyl)amino)-7-ethyl-1,4a,7-trimethyl-1,2,3,4,4a,4b,5,6,7,9,10,10a-dodecahydrophenanthrene-1-carboxylate (27). Rf = 0.43 (CHCl3); [α]D = + 34.81 (c 1.6, СНCl3); 1H NMR (400 MHz, CDCl3): δ = 0.75 (t, J = 7.5 Hz, 3 H, СН3-16), 0.83 (s, 3 Н, СH3-20), 0.89 (s, 3 H, СН3-17), 1.17 (s, 5 H, 17

22 3

119 9

1

44

11 9

10 10

H 8

55

СН3-19, Н-1,12), 1.23 (m, 2 Н, CH2-15), 1.28 (m, 1 Н, H-12), 1.43 (m, 1 Н, Н-6), 1.49, 1.52, 1.53, 1.60 (all m, 5 Н, CH2-2,11, H-3), 1.65, 1.70, 1.73 (all m, 3 Н, Н-3,1,6), 2.02

12 12

20

13 13 14

15 15

16 16

NH 1'

2'2'

6 7

H CO22Me CO

(m, 1 Н, Н-9), 2.24 (d, J = 12.4 Hz, 1 Н, Н-5), 2.45 (s, 3 Н, C(O)CH3), 3.34 (s, 3 Н, ОСН3), 3.95 (brd, J = 5.4 Hz, 1 Н, Н-7), 4.55 (d, J = 5.4 Hz, 1 Н, NН), 5.57 (s, 1 Н, Н-14), 6.55 (d, J = 8.3 Hz, 2 Н, Н-2’,6’), 7.75 (d, J = 8.3 Hz, 2 H, Н-3’,5’). 13C NMR (101 MHz, CDCl3): see Table S2. IR (neat): ν˜ = 756, 825, 954, 1064, 1078, 1124, 1147, 1180, 1278, 1307, 1357, 1384, 1433, 1446, 1460, 1485, 1525, 1573, 1597, 1597, 1658, 1724, 2852, 2868, 2945, 3373 cm –1. UV (EtOH) λmax nm (lgε): 238 (3.80), 335 (4.38). MS 3'

118 8

27

6' 6' 5' 5'

4'4'

O

11

(EI): m/z (%) = 451 (5), 287 (28), 266 (23), 257 (29), 245 (11), 241 (12), 227 (28), 166 (39), 159 (10), 151 (11), 145 (19), 135 (11), 119 (36), 109 (18), 105 (14), 95 (17), 93 (12), 91 (24), 85 (70), 82 (100), 47 (17), 28 (8). HRMS calcd. for C29H41O3N: 451.3081, found 451.3085.

(1R,4aR,4bR,7S,8S,10aR)-Methyl 8-((4-acetylphenyl)amino)-7-ethyl-1,4a,7-trimethyl-1,2,3,4,4a,4b,5,6,7,8,10,10a-dodecahydrophenanthrene-1-carboxylate (36). Crystallized from MeOH, m.p. 163165oС; Rf = 0.43 (CHCl3); [α]D = - 196.39 (c 1.6, СНCl3); 1H NMR (400 MHz, CDCl3): δ = 0.73 (t, J = 7.5 Hz, 3 H, СН3-16), 0.84 (s, 3 Н, СH3-17), 0.87 (s, 3 H, СН3-20), 1.07

17 17

12 11 11 13 14 99 14

20 20

11

2

3

10

4

16

NH 1'

H 8 H 7 66

5

(m, 1 Н, Н-1), 1.22 (s, 3 H, СН3-19), 1.21-1.28 (m, 2 H, Н-15), 1.36-1.45 (m, 4 Н, CH2-12, H-11,2), 1.50-1.61 (m, 6 Н, CH2-6,3, H-2,11), 1.72 (dd, J = 11.8, 2.6 Hz, 1 Н, Н-

15

1'

H Me CO2Me

5), 1.80 (m, Jgem = 13.4 Hz, 1 Н, Н-1), 1.92 (m, 1 Н, Н-9), 2.48 (s, 3 Н, C(O)CH3), 3.53 (s, 3 Н, ОСН3), 3.56 (brd, 1 H, J = 5.6 Hz, H-14), 3.67 (d, 1 H, J = 5.6 Hz, NH), 5.58 (d, J = 5.4 Hz, 1 Н, Н-7), 6.55 (d, J = 8.7 Hz, 2 Н, Н-2’,6’), 7.77 (d, J = 8.7 Hz, 2 Н, Н-3’,5’). 13C NMR (101 MHz, CDCl3): see Table S4. IR (neat): ν˜ = 592, 829, 1076, 1103,

2' 2'

1122, 1145, 1180, 1245, 1280, 1309, 1359, 1384, 1433, 1460, 1529, 1573, 1595, 1651, 1724, 2870, 2929, 3384 cm –1. UV (EtOH) λmax nm (lgε): 238 (3.7), 337 (4.4). MS

3'

6'

4'

36

(EI): m/z (%) = 451 (38), 317 (32), 287 (33), 258 (21), 257 (100), 227 (20), 161 (80), 145 (15), 136 (14), 135 (11), 121 (25), 120 (21), 105 (15), 95 (11), 93 (11), 91 (14), 81

5' 5'

O

(11), 55 (14), 41 (11); calcd. for C29H41O3N: 451.3081, found 451.3079.

(1R,4aR,4bR,7S,9S,10aR)-Methyl 7-ethyl-1,4a,7-trimethyl-9-(methyl(4-nitrophenyl)-amino)-1,2,3,4,4a,4b,5,6,7,9,10,10a-dodecahydrophenan-threne-1-carboxylate (38). Rf = 0.66 (CHCl3); [α]D = - 157.78 (c 0.3, СНCl3); 1H NMR (600 MHz, CDCl3): δ = 0.61 (t, J = 7.5 Hz, 3 H, СН3-16), 0.87 (s, 3 Н, СH3-20), 1.10 (q, J = 7.5 Hz, 2 Н, CH2-15),

17 11 9

20 22 3

1

10

13 13 14 14

16 16

15 15

7.9, 1.8 Hz, 1 Н, Н-9), 2.04 (dd, J = 12.8, 1.8 Hz, 1 Н, Н-5), 2.93 (s, 3 H, CH3-N), 3.61 (s, 3 Н, ОСН3), 4.24 (dd, J = 11.9, 3.0 Hz, 1 Н, Н-7), 4.95 (brs, 1 Н, Н-14), 6.57 (d, J

H 88

5

44

1.13 (m, 1 H, H-1), 1.24 (s, 6 H, СН3-19,17), 1.32 (m, 3 Н, CН2-12, H-6), 1.50- 1.63 (m, 4 H, CH2-2, H-3,11), 1.69 (m, 2 Н, Н-11,3), 1.72-1.83 (m, 2 Н, Н-1,6), 1.89 (dd, J =

12

77

6

NMe1'1'

H H 18

6' 6'

38

5'

C NMR (151 MHz, CDCl3): see Table S4. IR (neat): ν˜ = 754, 786, 827, 1109, 1149, 1197, 1211, 1244, 1317,

13

1386, 1460, 1492, 1512, 1595, 1683, 1726, 2852, 2871, 2929 cm–1. UV (EtOH) λmax nm (lgε): 232 (3.6), 314 (2.9), 394 (3.9). MS (EI): m/z (%) = 468 (21), 328 (32), 317

3' 3'

CO22Me CO

19 19

= 8.8 Hz, 2 Н, Н-2’,6’), 8.07 (d, J = 8.8 Hz, 2 Н, Н-3’,5’).

2'2'

NO22 4' NO

(19), 258 (16), 257 (70), 254 (19), 253 (100), 121 (21), 187 (17), 84 (26), 82 (42), 55 (26), 43 (25), 41 (31), 34 (8); calcd. for C28H40O4N2: 468.2983, found 468.2978.

(1S,4aS,4bS,7R,9S,10aS)-Methyl

7-ethyl-9-(((1R,4aR,4bR,7S,9R,10aR)-7-ethyl-1-(methoxy-carbonyl)-1,4a,7-trimethyl-1,2,3,4,4a,4b,5,6,7,9,10,10a-dodecahydrophenanthren-9-yl)oxy)-1,4a,7-

trimethyl-1,2,3,4,4a,4b,5,6,7,9,10,10a-dodecahydrophenanthrene-1-carboxylate (39). Rf = 0.66 (CHCl3); [α]D = + 60 (c 0.3, CHCl3); 1H NMR (600 MHz, CDCl3): δ = 0.76 (s, 6 Н, 2СH3-20), 0.83 (t, J = 7.5 Hz, 6 H, 2СН3-16), 0.88 (s, 6 H, 2СН3-17), 1.05 (m,

17 17 11 11 9

20 20 2 33

11

44

10 10

12 12

H 88

55

7 66 7

H 119 9

4 Н, 2Н-1,6), 1.18 (s, 6 H, 2СН3-19), 1.20 (m, 2 Н, 2H-15), 1.23-1.27 (m, 6 Н, 2CH2-12, 2H-3), 1.30 (m, 2 Н, 2H-15), 1.39 (m, 2 Н, 2Н-11), 1.53 (m, 8 Н, 2CH2-2, 2Н-

15 15

13 13 14 14

CO 2Me

H H

O O

CO2Me CO

11,6), 1.57 (m, 2 Н, 2Н-3), 1.68 (m, 2 Н, 2Н-1), 1.96 (m, 2 Н, 2Н-9), 2.40 (dd, J = 12.4, 2.5 Hz, 2 Н, 2Н-5), 3.51 (dd, J = 4.6, 2.4 Hz, 2 Н, 2Н-7), 3.80 (s, 6 Н, 2ОСН3), 5.17 (brs, 2 Н, 2Н-14). 13C NMR (151 MHz, CDCl3): see Table S4. IR (neat): ν˜ = 1037, 1060, 1082, 1122, 1143, 1186, 1245, 1384, 1433, 1460, 1597, 1728, 2850, 2871,

H H

118 8

12 39

2925, 2945, 3435 cm–1. UV (EtOH) λmax nm (lgε): 243 (3.6), 306 (2.7). MS (EI): m/z (%) = 650 (3), 334 (72), 317 (75), 287 (42), 257 (100), 227 (13), 166 (47), 145 (10), 121 (37), 109 (17), 95 (17), 81 (15), 41 (9). HRMS calcd. for C42H66O5: 650.4905. found 650.4899.

(1R,4aR,4bR,7S,9S,10aR)-Methyl 7-ethyl-1,4a,7-trimethyl-9-((4-nitrophenyl)amino)-1,2,3,4, 4a,4b,5,6,7,9,10,10a-dodecahydrophenanthrene-1-carboxylate (40). 17

Rf = 0.66 (CHCl3); 1H NMR (400 MHz, CDCl3): δ = 0.64 (t, J = 7.7 Hz, 3 H, СН3-16), 0.84 (s, 3 Н, СH3-20), 0.85 (s, 3 H, СН3-17), 1.14 (m, 3 Н, CH2-15, H-1), 1.21 (s, 3 H,

12 12

11 13 14 9 14

20 2 3

1

10 10

55

44

19

СН3-19), 1.29 (m, 2 Н, CН2-12), 1.42 (m, 1 Н, Н-6), 1.49-1.77 (m, 8 Н, CH2-11,2,3, Н-6,1), 1.89 (m, 1 Н, На -9), 2.07 (dd, J = 12.4, 2.8 Hz, 1 Н, Н-5), 3.65 (s, 3 Н, ОСН3), 3.82

16

15

H 8

(ddd, J = 12.1, 4.8, 2.4 Hz, 1 Н, Н-7), 3.87 (m, 1 Н, NH), 5.28 (s, 1 Н, Н-14), 6.45 (d, J = 8.8 Hz, 2 Н, Н-2’,6’), 8.04 (d, J = 8.8 Hz, 2 Н, Н-3’,5’).

7 6

see Table S4.

2' HN 1'1' HN

H CO2 Me

13

C NMR (101 MHz, CDCl3):

3'

18

40 40

6'

4'

5'

NO22

(1R,4aR,4bR,7S,9R,10aR)-Methyl 7-ethyl-1,4a,7-trimethyl-9-(phenyl-sulfonamido)-1,2,3,4,4a,4b,5,6,7,9,10,10a-dodecahydrophenanthrene-1-carboxylate (42). M.p..=138oC (methanol); Rf = 0.54 (CHCl3); [α]D = - 3.98 (c 1.0, СНCl3); 1H NMR (600 MHz, CDCl3): δ = 0.66 (t, J = 7.5 Hz, 3 H, СН3-16), 0.73 (s, 3 Н, СH3-20), 0.76 (s, 3 H,

17 17

11 9

20 2 33

1 44

10 10

13 13 14

16

15 15

(m, 3 Н, CH2-2, Н-11), 1.61 (m, 2 Н, H-6,3), 1.67 (m, 2 Н, Н-1,3), 1.87 (dd, J = 8.3. 1.6 Hz, 1 Н, Н-9), 2.20 (dd, J = 12.4, 1.8 Hz, 1 Н, Н-5), 3.68 (brd, J = 3.4 Hz, 1 Н, Н-7),

H 8

5

3.69 (s, 3 Н, ОСН3), 4.77 (d, J = 3.4 Hz, 1 H, NH), 5.11 (s, 1 Н, Н-14), 7.46 (m, 2 Н, Н-3’,5’), 7.52 (brt, J = 7.2 Hz, 1 Н, Н-4’), 7.82 (d, J = 7.6 Hz, 2 Н, Н-2’,6’).

7

6

H CO2Me CO

19 19

СН3-17), 0.97 (m, 1 Н, Н-12), 1.00 (q, J = 7.5 Hz, 2 Н, CH2-15), 1.09 (dt, J = 13.0, 4.3 Hz, 1 Н, Н-1), 1.14 (s, 3 H, СН3-19), 1.21 (m, 1 Н, H-12), 1.34 (m, 2 Н, H-6,11), 1.51

12 12

O O

HN S

1'

O

42

6'

C NMR

(151 MHz, CDCl3): see Table S4. IR (neat): ν˜ = 530, 555, 582, 646, 691, 718, 972, 1040, 1061, 1094, 1123, 1163, 1192, 1244, 1294, 1327, 1341, 1387, 1416, 1447, 1460,

2'2'

18 18

13

3'3'

1720, 2864, 2928, 2947, 3306, 3421 cm–1. UV (EtOH) λmax nm (lgε): 222 (3.83), 265 (2.81). MS (EI): m/z (%) = 473 (1), 445 (1), 316 (31), 301 (31), 288 (23), 287 (100),

4'4'

257 (25), 237 (35), 227 (55), 166 (48), 145 (25), 123 (30), 109 (24), 107 (25), 105 (27), 95 (30), 93 (26), 91 (28), 81 (28), 79 (22), 77 (33), 67 (20), 55 (27), 41 (25); calcd.

for C27H39O4NS: 473.2594, found 473.2602. (1R,4aR,4bR,7S,9R,10aR)-Methyl 9-((tert-butoxycarbonyl)amino)-7-ethyl-1,4a,7-trimethyl-1,2,3,4,4a,4b,5,6,7,9,10,10a-dodecahydrophenanthrene-1-carboxylate (44). Rf = 0.49 (CHCl3); [α]D = + 2.27 (c 0.4, СНCl3). 1H NMR (400 MHz, CDCl3): δ = 0.77 (t, J = 7.5 Hz, 3 H, СН3-16), 0.79 (s, 3 Н, СH3-20), 0.87 (s, 3 H, СН3-17), 1.10 (m, 2 Н,

17 17

22 3

19

11 4

11 11 99

10

H 88

5

13 14

15

16 16

O

7 6 7

N N H H

H H CO22Me 18 18

Н-1,12), 1.17 (s, 3 H, СН3-19), 1.22 (m, 1 Н, H-12), 1.24 (q, J =7.5 Hz, 2 Н, CH2-15), 1.41 (s, 9 H, C(CH3)3), 1.46-1.63 (m, 7 Н, CH2-2,11,3, Н-6), 1.66 (m, 1 Н, Н-6), 1.70 (m,

12

20 20

44

1 Н, Н-1), 1.89 (dd, J = 7.9, 1.8 Hz, 1 Н, Н-9), 2.02 (dd, J = 12.6, 1.8 Hz, 1 Н, Н-5), 3.63 (s, 3 Н, ОСН3), 4.05 (brs, 1 Н, Н-7), 4.82 (brs, 1 H, NH), 5.53 (s, 1 Н, Н-14).

13

C

NMR (101 MHz, CDCl3): see Table S4. IR (neat): ν˜ = 1026, 1047, 1172, 1244, 1365, 1388, 1462, 1489, 1720, 2852, 2870, 2949, 3442 cm . UV (EtOH) λmax nm (lgε): 243 –1

OC(CH OC(CH3) 3

(2.6). MS (EI): m/z (%) = 433 (1), 332 (16), 317 (20), 316 (35), 302 (13), 301 (41), 288 (21), 287 (100), 257 (14), 256 (12), 241 (11), 227 (13), 209 (9), 85 (20), 83 (30), 57 (17), 41 (7); calcd. for C26H43O4N: 433.3183, found 433.3187.

(1R,4aR,4bR,7S,9R,10aR)-Methyl 9-amino-7-ethyl-1,4a,7-trimethyl-1,2,3,4,4a,4b,5,6,7,9,10,10a-dodecahydrophenanthrene-1-carboxylate (45).

13

Rf = 0.43 (CHCl3); [α]D = + 25.59 (c 0.3, СНCl3). 1H NMR (400 MHz, CDCl3): δ = 0.76 (s, 3 Н, СH3-20), 0.78 (t, J = 7.5 Hz, 3 H, СН3-16), 0.87 (s, 3 H, СН3-17), 1.17 (s, 3 H, СН3-19),

17 17 11 11 99

20 20

22 3

19

11 4

10

1.22 (m, 5 Н, CH2-15,12 H-1), 1.38-1.71 (m, 7 Н, CH2-2,11,3, Н-6), 1.90-2.13 (m, 2 Н, Н-6,1), 2.18 (dd, J = 7.9, 1.8 Hz, 1 Н, Н-9), 2.29 (dd, J = 12.2, 2.4 Hz, 1 Н, Н-5), 3.19 (m, 2 Н,

12

13 14

15

16 16

H 88

5

18 18

C NMR (101 MHz, CDCl3): see Table S4. IR (neat): ν˜ = 1061, 1105, 1115, 1130, 1150, 1177, 1190,

13

1244, 1385, 1460, 1726, 2853, 2868, 2928, 2945 cm . UV (EtOH) λmax nm (lgε): 231 (3.34), 256 (3.07). MS (EI): m/z (%) = 332 (5), 330 (3), 319 (1), 318 (3), 316 (12), 287 (29), 257 –1

7 6 7

H H CO22Me

NH2), 3.66 (s, 3 Н, ОСН3), 3.72 (d, J = 3.8 Hz, 1 Н, Н-7), 5.40 (s, 1 Н, Н-14).

NH2 NH

(14), 256 (12), 241 (18), 227 (40), 187 (12), 171 (11), 165 (45), 159 (10), 150 (23), 145 (20), 137 (15), 136 (100), 133 (13), 131 (14), 119 (13), 107 (11), 105 (16), 95 (16), 93 (13), 91

45

(16), 81 (11), 79 (14), 67 (7), 55 (10); calcd. for C21H35O2N: 333.2662, found 332.2590.

Table S1. 13C NMR Spectral data for compounds 4-7, 10-13 (CDCl3, δ, ppm). C atom

4

5

6

7

10

11

12

13

38.78

38.22

37.99

17.84

18.03

18.06

1

38.12

36.43

37.08

38.16

2

18.11

18.06

18.23

18.04

3

36.54

35.93

36.25

36.43

37.05

36.69

37.06

36.81

4

47.14

44.30

46.93

47.31

46.77

46.28

46.85

47.17

5

43.12

50.26

44.09

43.90

42.91

44.73

42.94

47.43

6

29.25

127.20

116.44

28.56

29.73

24.89

29.77

32.49

7

55.52

130.97

121.65

45.29

56.39

125.02

56.40

56.24

8

134.13

134.80

131.79

133.71

133.95

136.32

134.20

118.42

9

47.10

50.57

145.77

48.48

47.32

47.52

47.16

49.80

10

38.07

36.43

43.32

37.99

38.09

35.00

38.13

37.87

11

18.35

18.68

25.70

18.71

18.33

19.31

18.33

18.86

12

32.67

33.13

32.42

33.14

32.75

31.21

32.96

32.83

13

34.24

35.02

31.66

34.46

34.28

36.61

34.16

33.85

14

138.10

135.75

38.31

137.42

138.58

62.44

137.83

131.26

38.26 18.00

14

15

35.96

35.87

36.33

36.43

35.93

32.24

35.92

35.25

16

8.08

8.30

8.04

8.34

8.14

7.40

7.96

8.01

17

25.06

26.92

25.04

25.48

24.91

20.95

24.78

25.53

18

178.52

178.77

179.03

178.85

179.00

178.84

1798.99

178.87

19

17.00

17.11

21.65

16.99

16.82

17.41

16.80

17.00

20

14.48

13.61

17.11

15.21

14.69

15.28

14.60

15.05

1’

144.26

135.08

152.44

152.77

147.97

148.68

2’

131.83

135.46

111.69

113.61

107.19

106.51

3’

126.86

132.07

126.18

126.37

149.08

149.30

4’

114.79

142.60

126.08

137.24

111.04

111.30

5’

135.58

118.16

126.18

126.37

129.23

129.42

6’

115.02

124.51

111.69

113.61

119.59

118.72

ОСН3

51.86

51.78

51.98

51.91

51.88

52.10

51.94

51.87

15

Table S2. 13C NMR Spectral data for compounds 15, 22-27 (CDCl3, δ, ppm). C atom

15

22

23

24

25

26

27

1

38.90

38.29

38.26

38.23

38.29

2

17.89

18.16

18.04

18.15

18.38

3

36.67

36.70

36.95

36.64

36.93

36.90

36.86

4

46.32

47.20

46.93

47.19

47.00

47.01

46.91

5

44.84

43.14

43.11

43.16

42.99

42.98

42.91

6

24.9

29.37

30.12

29.71

29.41

29.27

29.37

7

124.77

56.17

56.36

55.83

56.30

56.20

56.01

8

135.21

134.69

133.51

135.61

134.78

134.80

134.53

9

47.61

47.14

47.08

47.00

47.27

47.36

47.32

10

34.97

38.10

38.18

38.11

37.29

38.07

37.99

11

19.47

18.40

18.32

18.39

18.38

18.38

18.32

12

31.54

32.92

32.65

32.71

33.04

32.90

32.83

13

36.50

34.13

34.36

34.27

33.10

34.16

34.13

14

62.95

137.26

138.77

137.90

137.41

137.68

137.87

15

32.30

35.98

36.02

36.03

35.89

35.93

35.88

16

7.44

8.02

8.17

8.09

7.97

8.07

8.05

17

21.09

25.08

24.88

25.01

24.87

25.04

24.95

18

178.86

178.71

178.67

178.56

178.96

178.93

178.82

19

17.44

16.96

16.90

17.02

16.87

16.88

16.81

20

15.33

14.47

14.58

14.51

14.59

14.62

14.59

38.31 18.10

38.25 18.02

16

1’

148.43

143.70

147.98

140.47

147.34

149.64

125.87

2’

107.58

110.36

118.03

130.95

109.81

112.54

111.96

3’

149.17

127.96

125.45

106.92

135.32

126.23

130.50

4’

111.30

113.22*

136.65

149.21

112.90

141.96

151.16

5’

129.39

117.23*

124.37

126.85

129.24

126.23

130.50

6’

119.73

132.23

109.93

116.70

116.56

112.54

111.96

51.84

51.87

52.12

51.95

51.78

51.79

51.79 196.15 25.85

ОСН3 С=O СН3 CF3

124.48

123.97

17

Table S3. 13C NMR Spectral data for compounds 28-35 (CDCl3, δ, ppm). C atom

28

29

30

31

32

33

34

35

1

39.03

38.13

38.92

38.05

38.95

38.04

2

18.21

18.10

17.96

18.19

17.94

18.10

3

36.12

36.46

36.67

36.43

36.58

36.85

36.84

36.85

4

47.40

47.33

46.38

47.14

46.37

47.23

46.34

47.20

5

43.54

43.79

44.65

42.57

44.81

47.49

44.80

47.50

6

26.87

28.58

24.87

30.75

24.87

32.61

24.86

32.62

7

43.97

45.34

123.88

79.60

124.51

56.17

124.24

56.01

8

132.55

136.08

135.91

134.71

135.32

131.13

135.61

131.17

9

51.37

48.28

47.48

46.80

47.64

49.85

47.49

49.86

10

36.91

38.01

34.95

37.73

34.96

37.87

34.89

37.84

11

19.18

18.69

19.60

18.31

19.53

18.90

19.44

18.89

12

32.99

33.08

31.83

32.97

31.54

32.96

31.40

32.84

13

34.73

34.39

36.55

34.13

36.48

33.85

36.25

33.85

14

138.21

136.65

63.52

137.05

63.19

134.25

62.29

134.10

15

36.12

36.21

32.42

36.28

32.30

36.24

32.28

36.26

16

8.31

8.42

7.48

8.27

7.46

8.05

7.45

8.09

17

25.94

25.57

21.12

25.34

21.16

25.60

21.10

25.62

18

178.65

178.89

178.88

179.03

178.86

178.96

178.92

178.94

19

16.96

17.04

17.55

16.95

17.48

17.03

17.01

17.01

20

15.49

15.18

15.38

14.50

15.32

15.08

14.69

15.07

38.89 18.06

38.01 18.07

18

1’

135.94

135.99

144.61

144.04

147.92

148.07

150.19

150.40

2’

140.44

131.25

110.86

109.29

110.37

108.75

112.75

126.42

3’

110.08

109.34

128.01

128.30

137.30

135.95

126.34

111.92

4’

129.59

141.47

113.30*

115.71

113.07

113.10

141.25

138.43

5’

118.29

115.21

117.10*

119.37

129.25

129.33

126.32

126.42

6’

127.59

127.15

132.23

132.55

116.99

116.04

112.75

111.92

ОСН3

52.26

51.98

51.80

51.75

51.80

51.11

51.83

52.12

123.29

125.85

123.69

118.02

CF3

Table S4. 13C NMR Spectral data for compounds 36, 38-40, 42, 44, 45 (CDCl3, δ, ppm). C atom

36

38

39

40

42

44

45

1

38.77

38.13

38.48

38.01

38.25

38.28

41.25

2

17.87

17.99

18.23

18.05

17.99

18.06

18.05

3

36.60*

36.97

36.20

36.90

36.80

37.03

37.68

4

46.30

47.19

47.36

46.91

46.71

47.76

47.02

5

44.75

46.98

42.63

43.77

42.67

47.05

42.18

6

24.86

28.85

31.51

29.35

30.66

29.09

32.99

7

124.20

61.68

73.30

56.07

57.21

51.83

53.97

8

135.76

130.95

134.88

133.35

133.89

134.81

134.36

9

47.52

50.26

46.73

47.42

47.60

50.08

46.65

10

36.63

37.24

37.91

37.85

37.42

37.48

38.01

19

11

19.31

18.90

18.29

18.89

18.18

18.43

18.33

12

31.20

32.44

36.55

32.51

32.85

33.45

36.92

13

32.24

34.04

34.08

33.95

33.74

34.09

35.92

14

62.21

131.96

136.36

131.57

137.63

137.34

136.02

15

35.00

36.10

33.18

36.27

35.40

35.85

33.94

16

7.43

8.15

8.39

8.12

7.89

8.12

8.11

17

21.00

26.06

25.34

25.53

24.66

28.48

25.17

18

178.81

178.77

179.18

178.77

178.65

178.70

179.07

19

17.41

17.07

17.07

17.04

16.84

16.65

16.79

20

15.24

15.27

14.23

15.11

14.60

14.50

14.22

1’

125.96

154.96

153.08

140.75

2’

111.98

110.76

111.74

127.06

3’

130.69

126.09

126.37

128.80

4’

151.69

136.80

137.43

132.20

5’

130.69

126.09

126.37

128.80

111.98 51.85

110.76 52.17 33.46

111.74 52.15

127.06 52.19

51.97

52.15

6’ ОСН3 NCH3 СH3 C(СH3)3 NHC(O)O C=O

25.86

52.05

28.44 78.84 160.25

196.08

20

S2. X-ray crystal structure analysis for compounds 5, 24, 27, and 36 The compounds 24, 27 crystallizes in the orthorhombic space groups P212121, while 5, 36 crystallizes in the monoclinic P21 group. The crystallographic data are listed in Table S5. Molecular structure of compounds 6, 24, 27, 36 is illustrated in Fig. 2. The obtained crystal structures were analyzed for short contacts between non-bonded atoms using PLATON [26] and MERCURY programs [27]. CCDC 1407201 (5), 1407203 (24), 1407202 (27), 1422327 (36) contain the supplementary crystallographic data for this paper. These data can be obtained free of charge via http://www.ccdc.cam.ac.uk/cgi-bin/catreq.cgi, or from the Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: (+44) 1223 336 033; or e-mail: [email protected].

Table S5. XRD data for compounds 5, 24, 27 and 36

Compound Empirical formula Formula weight Temperature K Crystal system Space group Unit cell dimensions a Å bÅ cÅ αo βo γo Volume Å3 Z Density (calcd.) Mg.m–3 Abs. coefficient mm–1 F(000) Crystal size mm3 Θ range for data collection ° Index ranges Reflections collected Independent reflections Completeness to θ % Data / restraints/ parameters Goodness-of-fit on F2 Final R indices I > 2σ(I) Final R indices (all data) Largest diff. peak / hole e.Å-3

5 C21H32O2 316.47 200(2) Monoclinic P21 6.3192(2) 12.2161(5) 12.2957(5) 90.00 104.082(2) 90 920.65(6) 2 1.142 0.071 348 0.8 x 0.4 x 0.04 1.7 – 27.5 -8 ≤ h ≤ 8, -15 ≤ k ≤ 15, -15 ≤ l ≤ 15 27580 4235 R(int) = 0.034 100.0 4235 / 1 / 213 1.15 R1 = 0.0444, wR2 = 0.1439 R1 = 0.0467, wR2 = 0.1488 0.22/ -0.23

27 C29H41NO3 451.63 296(2) Orthorhombic P212121 9.3376(4) 9.4039(4) 30.190(1) 90 90 90 2650.98(19) 4 1.132 0.072 984 0.5 x 0.5 x 0.80 1.4 – 26.0 -11 ≤ h ≤ 11, -11 ≤ k ≤ 9, -34 ≤ l ≤ 37 25551 5153 R(int) = 0.043 98.8 5153 / 0 / 304 1.06 R1 = 0.0537, wR2 = 0.1498 R1 = 0.0739, wR2 = 0.1685 0.44/ -0.22

24 C28H40N2O5 484.62 296(2) Orthorhombic P212121 9.5312(3) 32.961(1) 8.2760(4) 90 90 90 2600.0(2) 4 1.238 0.084 1048 0.50 x 0.30 x 0.20 1.2 - 25.7 -11 ≤ h ≤11, -40 ≤ k ≤40, -10 ≤ l ≤10 28442 4959 R(int )= 0.064 100.0 4959 / 0 / 322 1.12 R1 = 0.0384, wR2 = 0.1012 R1 = 0.0536, wR2 = 0.1204 0.20 / -0.28

36 C29H41NO3 451.63 296(2) Monoclinic P21 8.0363(3) 23.4011(9) 13.8684(6) 90 95.380(2) 90 2596.6(2) 4 1.155 0.073 984 0.40 x 0.30 x 0.20 1.5 – 26.1 -9 ≤ h ≤ 9, -28 ≤ k ≤ 28, -17 ≤ l ≤ 17 51381 10224 R(int) = 0.050 99.8 10224 / 1 / 607 1.06 R1 = 0.0444, wR2 = 0.1150 R1 = 0.0639, wR2 = 0.1383 0.21 / -0.18

21

Table S6. Parameters of the short inter-molecular and the selected intra-molecular contacts. Compound 5

Compound 27

Type interaction

Short contact

Value, Å

Type interaction

Short contact

Value, Å

intra

O1...H4

2.41

intra

N1...H5

2.55

intra

O1...H9

2.39

intra

O2...H3

2.55

D-H...A

D-H, Å

H...A, Å

D...A, Å

D-H...A,

intra

O2...H31

2.47

N1-H...O3

0.86

2.37

3.220(3)

168 °

C8’-H...O2

0.96

2.49

3.350(4)

150 °

C11-H...O2

0.97

2.55

3.487(4)

162 °

H-bond

Compound 24

Compound 36

Type interaction

Short contact

Value, Å

Type interaction

Short contact

Value, Å

inter

O2...H15b

2.61

inter

O1a...H43

2.54

inter

O3...H14

2.63

inter

O2a...H50

2.57

inter

O5...H16a

2.65

intra

O3...N1

2.613(2)

D-H...A

D-H, Å

H...A, Å

D...A, Å

D-H...A,

intra

N1...N2

2.933(2)

N1b-H...O2a

0.86

2.53

3.280(3)

146 °

intra

N1...H5

2.66

N1a-H...O3b

0.86

2.30

3.145(3)

165 °

H-bond

Note, that normal O..H, N...H and N...N contacts are 2.68, 2.74 and 3.27 Å correspondingly [Rowland R.S. and Taylor R. // J. Phys. Chem. – 1996. – 100. – P. 7384].

22

S3. 1H and 13C spectra of synthesized compounds 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21.

1

H and 13C spectra of compound 4 H and 13C spectra of compound 5 1 H and 13C spectra of compound 6 1 H and 13C spectra of compound 7 1 H and 13C spectra of compound 10 1 H and 13C spectra of compound 12 1 H and 13C spectra of compound 13 1 H and 13C spectra of compound 15 1 H and 13C spectra of compound 22 1 H and 13C spectra of compound 23 1 H and 13C spectra of compound 24 1 H and 13C spectra of compound 25 1 H and 13C spectra of compound 27 1 H and 13C spectra of compound 29 1 H and 13C spectra of compound 30 13 C spectra of compound 31 1 H and 13C spectra of compound 33 1 H and 13C spectra of compound 35 1 H and 13C spectra of compound 38 13 C spectra of compound 39 1 H and 13C spectra of compound 42 1

23

H 8

5

3

6

4

13 14

1.20

15

0.92

10

12

16

NO2

7

2'

NH 1'

H

1.24

1

2

11 9

3.36

17

20

0.87

Compound 4

3'

CO2Me 6'

18

4'

4

5'

0.74

19

1.00

1.12

1.17 8.0

8.5

1.08

7.5

1.06

7.0

5.5

6.0

0.95 5.0 4.5 Chemical Shift (ppm)

2.93 4.0

3.5

0.94 3.0

0.89

2.5

1.74

2.31

1.56

1.00

6.5

2.08

4.16

6.56

8.48

8.15

6.90

5.59

0.75

7.25

Chloroform-d

3.27 3.86

18.09

1.5

2.0

8.96 1.0

17

18

4

4'

178.44

5'

8.00

136

16.92

144

14.41

47.03

152

114.71

160

43.04

51.78

114.94

138.03

168

24.98

55.44

126.78

135.50

176

18.27 18.03

3' 6'

29.17

2'

NH 1'

CO2Me

29.59

6

4

16

NO2

7

H 19

15

H 8

5

38.04 35.88 34.17 32.59

10

47.06

1

134.05

3

13 14

144.18

2

12

77.13 76.92 76.71

11 9

20

128

120

112

104

96 88 Chemical Shift (ppm)

80

72

64

56

48

40

32

24

16

8

24

1

2 3

9

10 5

15

0.72

0.91

3.65

17 12 11 13 14

20

1.19

Compound 5

16

8 7

6

4 H

5

CO 2Me

18

1.24

0.79

19

5 4

15

4.0 Chemical Shift (ppm)

3.0

1.13 2.5

0.88

1.36 1.26 1.26

1.71

1.56 1.41

1.12 1.11

1.61 1.59 1.34

0.98 3.5

3.62 3.58

2.0

1.5

1.0

50.25

9

10

4.5

16

8 7

50.55

3

1

135.74

20 2

3.26 5.0

130.96

5.5

17 12 11 13 14

2.01

2.00

6.0

127.19

6.5

1.75

5.24

5.97 5.96 5.94 5.94

1.00 7.0

2.69

5.25

7.25

0.81

Chloroform-d

6

13.60

8.31

5

26.92

18

51.96

19

17.10

H

CO 2Me

178.79

Chloroform-d

35.01

46.29

134.78

18.65

160

152

144

136

128

120

112

104

96 88 Chemical Shift (ppm)

80

72

64

56

48

40

18.06

35.92 36.41

168

33.10

176

32

24

16

8

25

Compound 6 17

3

9

10 5

1.23

13 14

16

15

0.78

1 2

12

3.63

11

20

8 7

6

4 H

6

2.00 7.0

6.5

6.0

4.13

5.5

5.0

4.5

4.0 Chemical Shift (ppm)

1.83 14.20 3.5

3.0

2.5

2.0

1.5

0.75 0.86

0.72

1.21 1.20 1.19 1.16 1.15

2.11

2.03 2.00

3.65

5.33 5.33

7.25

Chloroform-d

1.94 1.92 1.75 1.86 1.69 1.86 1.61 1.55 1.58 1.40 1.38 1.25

1.97

0.77

18

0.96

CO2Me

19

3.18 1.0

18

25.04

H

CO2Me

19

6

32.42

43.32

144

136

128

120

112

104

96 88 80 Chemical Shift (ppm)

72

64

56

48

40

32

24

18.23

152

25.70

160

31.66

36.25 37.08 38.31

77.00

168

29.68

46.93

145.77

131.79

179.03

Chloroform-d

176

8.04

6

4

21.65

16

17.11

15

8 7

44.09

5

51.87

3

9

10

13 14

121.65

1 2

12

116.44

17 11

20

16

8

0

-8

26

Compound 7 17

10

H

5

6

4

8

16

6'

7

5'

1'

H

CO2Me

2'

4' 3'

7

NH 2

0.95 0.89

1

15

1.21

3

13 14

3.52

2

12

11 9

20

0.84

NO 2

7.5

7.0

1.49

1.00 6.5

2.96

5.5

6.0

1.88

3.40

0.96

8.0

5.0

4.5 4.0 Chemical Shift (ppm)

3.5

1.77 3.0

1.63

1.75

5.42 6.73

8.01

0.97

0.83

7.25

Chloroform-d

4.37

2.0

2.5

3.76 4.75 1.5

8.41 1.0

17

H

CO2Me

2'

4'

3'

NH 2

NO 2

25.48

51.78

48.48

137.42

7

5'

1'

8.34

6

6'

7

16.99

4

16

15

8

15.21

H

5

43.90

10

45.29

1

118.16

3

13 14

124.51

2

12

135.08

11 9

20

132.07

144

136

18.04

152

28.56

160

36.43

168

33.14

38.16

135.46

176

18.71

34.46

47.31

133.71

142.60

178.85

Chloroform-d

128

120

112

104

88 96 Chemical Shift (ppm)

80

72

64

56

48

40

32

24

16

8

27

Compound 10 Chloroform-d

2 3

1

10

12

13 14

15

16

3.45

7.25

17 11 9

20

H 8

5 4

6

7

NH 1'

H

2' 3'

CO2 Me

19

18

10

6'

4' NO2

1.93

8.0

7.5

7.0

0.96

6.5

6.0

0.85

5.5

5.0

0.88 4.5 4.0 Chemical Shift (ppm)

0.76 0.75

1.18 1.17 1.14

2.27 2.24 2.01 1.77 1.76 1.73 1.61 1.58 1.57 1.55 1.48 1.43 1.40 1.27 1.25

3.99

4.98 4.96 2.05

3.65 3.55

5.62

6.57 6.55

8.05 8.03

0.78

0.92

0.86

1.21

5'

2.60 3.5

3.0

2.5

2.0

1.5

1.0

17

7

4

6

NH 1'

H 19

15

16

2' 3'

CO2 Me 18

10

6'

24.91

138.58

56.39

51.98

5'

4' NO2

160

152

144

136

128

120

112

104

96 88 Chemical Shift (ppm)

80

72

64

56

48

38.09

168

18.00 18.33

38.26

46.77

176

29.73 32.75 34.28 35.93

133.95

152.44

179.00

Chloroform-d

8.14

H 8

5

16.82 14.69

10

42.91

1

47.32

3

13 14

111.69

2

12

126.18

11 9

20

40

32

24

16

8

28

Compound 12 17

10

15

7

6

2'

NH 1'

H CO 2Me

19

16

H 8

5 4

0.86

1

NO2 3'

18

6'

12

4'

0.90

3

13 14

5'

7.5

1.12

1.00

7.0

6.0

6.5

0.96 5.5

5.0

4.5

4.0 Chemical Shift (ppm)

0.94 3.0

0.78 0.83 0.71

1.20

0.62

1.19 1.16 1.08

1.57 1.56 2.02 1.79 1.78 1.74 1.72 1.65

2.30 2.30 2.27 2.26

3.65 3.60

3.07 3.5

1.47 1.43 1.36 1.41

3.51

6.89 6.87

3.93

1.05

5.63

7.21

2.56

7.19

7.45 7.44 7.43

1.24

0.84 0.73

7.25

2

12

1.21

11 9

20

3.47

Chloroform-d

0.94

2.5

2.0

1.5

1.0

17

6

18

2'

NH 1'

H CO 2Me

NO2 3'

12

6'

4' 5'

29.65

77.32 77.00 76.69

149.08 147.97

178.99

Chloroform-d

128

120

112

7.96

136

16.80

144

51.88

152

42.94

47.16

56.40

160

107.19

119.59

168

24.78

111.04

129.23

137.83

176

18.33 18.03

4

16

15

34.16

7

29.77

H 8

5

38.13

10

32.96

19

1

38.22 37.06

3

13 14

46.85

2

12

134.20

11 9

20

104

88 96 Chemical Shift (ppm)

80

72

64

56

48

40

32

24

16

8

29

Compound 13 17 11 9

20

16

15

H 8 7

6

4

NH 1'

H

2'

NO2 3'

CO2 Me

19

18

6'

13

4' 5'

0.61

1.20

0.85 0.83

10 5

3

13 14

3.64

1

2

12

1.40 1.21

1.05

1.00

7.0

6.5

6.0

1.02

5.5

5.0

4.5

3.19

4.0 Chemical Shift (ppm)

1.24 1.21

1.04 1.16 2.28 3.5

3.0

2.5

2.0

0.62 0.60 0.87 0.86 0.80

1.53 1.43

1.75

1.90

2.07

3.51

3.70 4.02

6.79 6.78

7.44 7.43

7.19

5.34

1.14 1.12

7.29 7.21

7.25

Chloroform-d

3.76 1.5

7.01 1.0

3.22 0.5

17

6

NO2

Chloroform-d

3'

18

13

6'

4' 5'

149.30 148.68

178.87

2'

NH 1'

CO2 Me

18.86 18.06

4

7

H 19

16

15

H 8

5

36.25 33.85 32.83 32.49

10

47.17

1

37.99

3

13 14

77.21 77.00 76.78

2

12

133.84

11 9

20

15.05

25.53

56.24

52.10

63.00

8.01

17.02

47.43 49.80

106.51

118.72

131.26 129.42

111.30

176

168

160

152

144

136

128

120

112

104 96 88 Chemical Shift (ppm)

80

72

64

56

48

40

32

24

16

8

30

Compound 15 17 11 9

10

H 8

5

3

6

4

15

13 14

16 3.51

1 2

12

20

NH 1'

2'

7

NO2

H CO2 Me

3'

6'

15

4'

1.21

0.88

0.86

5'

2.30

1.00

7.0

6.5

6.0

5.0

4.5 4.0 Chemical Shift (ppm)

2.02

3.5

3.0

2.5

2.30 5.85

2.0

4.21

1.5

0.90

1.30

1.07

3.46

4.30

5.5

0.73

0.78 0.76

0.98

3.64

5.60

6.86 6.84

1.04

7.5

1.94 1.80 1.67 1.66 1.64 1.50

7.21 7.20

7.43 7.42

7.42

0.77

7.25

Chloroform-d

7.05 1.0

17

2'

1'

7

NO2 3'

6'

4'

5'

62.95

51.84

129.39

124.77

119.73

19.47

24.90

17.89

31.54

148.43

38.90

34.97

46.32

149.17

178.86

36.50

32.30

Chloroform-d

7.44

15

107.58

H CO2 Me

17.44

6

16

NH

15.33

5 4

15

21.09

H 8

13 14

47.61

10

12

44.84

3

11 9

111.30

1 2

20

135.21

176

168

160

152

144

136

128

120

112

104

96 88 Chemical Shift (ppm)

80

72

64

56

48

40

32

24

16

8

31

0.90 0.86 0.73

Chloroform-d

1.21

3.42

Compound 22

12

9

3

10

7

6

H CO2Me

19

18

Br HN

2'

1'

3'

22

0.35

16

8

H

5 4

15

6'

4' 5'

0.75

1 2

0.40

13 14

1.19

7.25

17

11

20

0.45

1.17 1.16

1.76 1.75 1.58 1.58 1.56 1.56

3.54 3.65

3.96 3.95

0.15

5.53

6.75

7.09 7.07

0.20

6.62 6.61 6.59

6.77

1.22

0.25

7.40 7.38

Intensity

0.30

0.10

0.05

0 0.94

0.98

7.5

0.89 0.93

7.0 Chemical Shift (ppm)

1.00 6.5

6.0

5.5

1.28 5.0

4.5

4.0

2.77

0.85

3.5 3.0 Chemical Shift (ppm)

0.88

2.5

3.20

2.0

7.08 1.5

8.67

6.85 1.0

17

3'

22

6'

4'

144.03 143.70

178.71

5'

18.16 18.40

2'

1'

34.13

HN

29.37

18

Chloroform-d

Br

32.92

7

H CO2Me

19

16

8

38.29

6

47.20

H

5

77.41

10

4

110.36

3

134.69

1 2

15

76.58

13 14

9

36.70 35.98

12

11

20

8.02

43.14

47.14

127.96

14.47 16.96

25.08

56.17

51.87

115.69 117.23 119.33

113.22

137.26 132.23 132.53

176

168

160

152

144

136

128

120

112

104

96 88 80 Chemical Shift (ppm)

72

64

56

48

40

32

24

16

8

32

Compound 23 17

8.19

4

7

6

H 19

15

H 8

16

Cl NH 1'

2' 3'

0.92 0.87 0.77

3

5

1.57

10

7.25

2

13 14

1.22

1 Chloroform-d

12

3.52

11 9

20

CO2Me 18

6'

23

4' NO2

7.0

7.5

1.93 6.0

6.5

0.91 5.0 4.5 Chemical Shift (ppm)

5.5

4.0

0.93

3.5

3.0

1.41 1.30

2.00 1.86 1.85

2.33 2.30

2.97

0.96

3.46

2.0

2.5

1.16 1.15

1.66 1.59

1.00

8.0

3.65

4.04

5.59 5.57

8.01

7.99 7.98

1.08 1.04 8.5

1.45 1.26 1.25

5.63

6.71 6.69

1.24

0.75

5'

1.0

1.5

17

2' 3'

CO2Me 4' NO2

38.26

5'

136.65

178.67

147.98

23

6'

46.93

18

18.32 18.04

H 19

Chloroform-d

Cl NH 1'

30.12

7

6

16

32.65

5

15

38.18 36.02

H 8

77.25 77.00 76.75

10

4

13 14

118.03

3

11 9

133.51

1 2

12

20

128

120

112

104 96 88 Chemical Shift (ppm)

80

72

64

56

48

14.58 16.90

24.88

136

47.08

144

43.11

152

56.36

160

52.12

168

125.45

176

109.93

124.37

138.77

184

40

32

24

16

33

Compound 24 17

15

H 8

5

6

16

NO2

7

NH 1'

H

2'

1.20

4

10

3'

CO2 Me 6'

0.73

3.41

4.0

1.04 0.43

2.83

2.44

1.41 1.28

8.68

1.13 1.12

10.08

6.97 1.0

1.5

2.0

2.5

3.0

3.5

1.47

2.35 2.33

3.64 3.54

0.97 4.5 5.0 Chemical Shift (ppm)

5.5

1.24

1.59

1.00 6.0

6.5

7.0

7.5

2.08 2.06 1.81 1.80 1.85 1.77 1.74 1.62

3.77

1.120.97

1.12 8.0

8.5

4.14

8.49 8.47

7.09 7.06 7.06

6.88

6.90

5.57

7.58

1.57 1.56

5'

0.75

24

4' OMe

1.22

18

1.18

19

0.89

0.91 0.86

3

1.17 1.16

7.25

2

13 14

3.77

1

Chloroform-d

12

3.43

11 9

20

17

5

6

7

H

16

Chloroform-d

NO2 2'

NH 1'

3'

CO 2Me

18.39 18.15

29.71

17.04 14.53

149.21

178.56

38.11 36.64 34.27 36.03 32.79

4' OMe

38.23

24

5'

47.19

6'

43.18

18

51.96

19

15

H 8

10

4

134.38

1

130.95

3

13 14

140.47

2

12

77.25 77.00 76.74

11 9

20

8.09

16

8

55.83

14.51 17.02

25.01

43.16

47.00

51.95

106.92

116.70

126.85

137.90

176

168

160

152

144

136

128

120

112

104

96 88 Chemical Shift (ppm)

80

72

64

56

48

40

32

24

34

Compound 25 17

10

NH 1'

H CO2 Me

2'

0.91 0.86

CF3

0.74

7

6

4

19

16

1.21

15

H 8

5

3

13 14

3.39

1

2

12

11 9

20

3'

18

6'

25

4'

6.0

2'

CF3 3'

6'

4' 5'

124.48

0.79

1.16 1.19 1.15

7.97

116.56

25

NH 1'

1.73 1.73 1.70 1.64 1.57 1.55 1.54 1.50 1.44 1.31 1.42 1.29 1.24

16

16.87 14.59

6

H CO2 Me

18

1.0

24.87

4

19

15

H 8 7

1.5

42.99

5

2.0

2.5

47.27

10

3.0

51.78

1

3.5

56.30

3

4.0 Chemical Shift (ppm)

137.41

2

12

13 14

4.5

129.24

17 11 9

20

5.0

5.5

2.29 2.27 2.26

3.91 6.5

109.81

7.0

112.90

7.17

6.74 6.72

6.85

7.25 7.19

Chloroform-d

2.05 1.76

5.57

1.22

0.72

6.83

0.76

5'

Chloroform-d

134.78

152

144

136

128

120

112

88 96 104 Chemical Shift (ppm)

80

72

64

56

48

40

32

18.38

47.00

160

33.04 34.10 35.89 36.93 38.29

168

29.41

147.34

178.96 176

24

16

8

35

Compound 27

NH 1'

2'

2.45

H CO2Me

3'

18

27

6'

0.89

7

6

4

19

16

H 8

0.83

10 5

3

3.34

1 2

15

1.17

17 12 13 11 14 9

20

4'

5'

0.75

O

7.0

6.0

0.73

1.23 1.21 1.14 1.60

0.99

6.5

1.01

5.5

5.0

4.5 4.0 Chemical Shift (ppm)

0.98

0.62

1.04

1.28 1.25

1.70 2.02 2.00

2.26 2.23 2.92

1.73

3.15

2.03 7.5

3.66 3.64 3.61

3.95 2.67

1.52 1.43

5.57

6.56 6.54

7.76 7.74

2.65

7.25

Chloroform-d

4.05 1.11

3.5

3.0

2.5

2.0

1.5

1.0

17 12 11 13 14 9

15

16

NH 1'

2'

H 8 7

H CO2Me

Chloroform-d 3'

18

27

6'

4'

O

125.87

196.15

178.82

151.16

5'

144

136

8.05

152

16.81

160

14.59

168

24.95 25.85

176

42.91

51.79

111.96

130.50

184

47.32

56.01

137.87

192

18.32 18.02

6

37.99

5

38.25 36.86 34.13 32.83 29.37

19

10

4

46.91

3

77.42 77.00 76.58

1 2

134.53

20

128

120

112 104 96 Chemical Shift (ppm)

88

80

72

64

56

48

40

32

24

16

8

36

0.94

1.20

0.88

3.56

Compound 29

17

3

19

10

H

5 4

6

13 14

16

15

8 6'

7

H CO 2Me 18

5'

1' 2'

4'

3'

NH2

0.83

1 2

12

0.85

11 9

20

Br 1.24

29

1.06 6.0

3.01 1.01

5.5

4.5

5.0

2.28

3.5

4.0 Chemical Shift (ppm)

3.0

2.5

0.96

1.47

1.35 1.27

1.61 1.65

7.18

2.0

4.99

4.97

12.58 1.0

1.5

19

5 4

6

6'

7

H CO 2Me 18

5'

1' 2'

4'

3'

29

8.42

16

15

8

15.18

H

25.57

10

13 14

17.04

3

12

48.25

1 2

43.79

51.98

17

11 9

20

45.34

127.15

131.25

115.21

136.65

6.5

1.37

1.89 1.87 1.81

3.40 3.39

0.82

7.0

1.78

5.38 0.89

6.68 6.66

7.30

6.99 6.97 1.64

3.63

7.25

1.49

Chloroform-d

NH2

Br

109.34

152

144

136

128

120

112

104

96 88 Chemical Shift (ppm)

80

72

64

56

48

18.10 18.69

28.58

160

34.39 36.21 38.01

168

38.13

47.33

176

33.08

135.99

141.47

178.89

Chloroform-d

40

32

24

16

8

37

Compound 30

38

Compound 31 17

3

10

H 5

4

8

Chloroform-d 2' 3'

1'

6 7

N H

H 19

Br

CO2Me

5'

31

144.04

47.14

109.29

179.03

134.71

18

4' 6'

18.31

2

16

15

38.05 36.28 34.13 32.97 30.75

9 1

13 14

61.92

20

12

77.32 77.00 76.69

11

8.27

136

16.95

144

46.80

51.75

152

14.50 15.44

25.34

42.57

79.60

115.71

119.37

160

128.30

168

132.55

137.05

176

128

120

112

104

96 88 Chemical Shift (ppm)

80

72

64

56

48

40

32

24

16

8

39

3.64

Compound 33

0.86

7.25

Chloroform-d

1

10

2

1.20 15

16

H 8

5

3

4

7

6

NH 1' 2'

H

CF3 3'

CO2Me

19

0.84

17 12 13 11 9 14

20

18

6'

33

4'

4.0 Chemical Shift (ppm)

4.5

5.0

5.5

6.0

6.5

7.0

0.81 0.66 0.62 0.87

1.06

0.78 0.5

1.0

1.5

2.0

2.5

3.0

3.5

1.30

2.08 2.05 1.92 1.90 1.88 1.73 1.59 1.57 1.56 1.55 1.51

3.71 3.70

3.52

5.38

6.69 6.67

6.84

7.19

3.67

1.15 1.15

0.64

5'

77.00 76.75

Chloroform-d

12 11 13 9 14

20

16

15

H 8

5 4

6

7

H

NH 1' 2'

18

6'

4' 5'

47.23

178.96

148.07

134.25

33

CF3 3'

CO2Me

19

136

128

120

112

104

96 88 Chemical Shift (ppm)

80

72

64

56

48

40

32

24

8.05

144

56.17

152

47.49 49.85

160

15.08 17.03

52.11

168

25.60

108.75

116.04

113.10

129.33 131.13

176

18.90 18.10

3

10

32.96 32.61

2

38.04 37.87 36.85 36.24

1

77.26

17

16

8

40

Compound 35

1 2 3

4

10

16

H 8

5

7

6

H CO2Me

19

15

0.86 0.83

17 12 11 13 14 9

20

1.20

3.64

7.25

Chloroform-d

2' HN 1' 3'

18

6'

35

4'

CF 3

2.11 7.0

1.00

6.5

6.0

3.48

5.5

5.0

4.5

4.0 Chemical Shift (ppm)

1.14 2.57 11.78 3.5

3.0

2.5

2.0

16.82

1.5

0.87

0.76

1.06 1.11

1.13

0.66 0.63

1.24

1.89

7.5

1.56 1.56 1.48 1.38 1.51 1.30

3.74 3.72 3.70

2.07 2.04 1.88 1.75 1.73 1.72 1.71 1.67 1.59

5.36

6.52 6.50

7.35 7.32

1.16 1.14

0.65

5'

8.66 3.46 1.0

0.5

Chloroform-d

12 11 13 14 9

20 1 2 4

5

16

6

7

H CO2Me

19

15

H 8 2' HN 1' 3'

18

18.89 18.07

37.84

25.58 24.91

150.40

36.26 33.85 32.84 32.62

CF 3 47.20

5'

4'

38.01

6'

178.94

35

134.10

3

10

77.25 77.00 76.74

17

15.07 8.09

47.50

131.17

56.01

17.01

25.62

49.86 52.12

126.42 111.92

176

168

160

152

144

136

128

120

112

88 96 104 Chemical Shift (ppm)

80

72

64

56

48

40

32

24

16

8

41

1.24

Compound 38

17

H 8 7

NMe 1'

2' 3'

18

6'

38

1.33

5'

4' NO 2

2.93

2.01

1.86 7.5

7.0

1.12

1.00

6.5

6.0

5.5

5.0

0.90 4.5 4.0 Chemical Shift (ppm)

3.90

17

10

13 14

6

7

15

NMe 1'

H 19

1.69 1.57

3.25 0.5

Chloroform-d 16

2' 3'

CO2Me 18

6'

38

4' NO 2

47.19 136.80

154.96

38.13 37.24

130.95

5'

178.77

198.58

1.0

12

H 8

5 4

7.20

1.5

18.90 17.99

3

2.0

34.04

2

12.42

0.930.78 2.5

32.44

1

3.0

77.21 77.00 76.79

11 9

20

3.03 0.47

3.5

36.10

8.0

1.89

2.05 2.03

4.95

6.58

8.08

7.25

Chloroform-d

28.85

6

H CO2Me

19

3.61

5 4

16

15

0.87

10

1

13 14

0.61

11 9

2 3

12

20

8.15

26.06

33.46

17.07

46.98

50.26 52.17

61.68

131.96 126.09 110.71

192

184

176

168

160

152

144

136

128

120

112 104 96 Chemical Shift (ppm)

88

80

72

64

56

48

40

32

24

16

8

42

46.73

Compound 39

52.05

8.39

17.07

H

14.23

CO2Me

25.34

H

O

136.36

H H CO2Me

42.63

73.30

Chloroform-d

39

CH4

18.29

31.51 33.18 34.08 36.20 36.55 38.48

47.36

134.88

179.18

76.79

176

168

160

152

144

136

128

120

112

88 96 104 Chemical Shift (ppm)

80

72

64

56

48

40

32

24

16

8

43

0.76 0.73

1.14

3.69

Compound 42

1 2 3

10

12

13 14

6

7

H CO2 Me

19

16

15

H 8

5

4

0.66

17 11 9

20

O

HN

2' 1'

S

3'

18

O

42

6'

4' 5'

0.99 4.76

2.19

7.25

1.35

1.52

0.65

5.11

7.82

7.46

Chloroform-d

2.09 0.00

2.10

1.00 5.0

5.5

6.0

6.5

7.0

7.5

0.97

1.00

4.37 4.0 4.5 Chemical Shift (ppm)

1.07 4.39

2.25 3.213.08 5.49 0.5

1.0

1.5

2.0

2.5

3.0

3.5

128.80 127.06

8.0

17 11 9

16

H 8 6

7

H CO2 Me

O

HN

2' 1'

S

3'

18

O

42

4'

6'

52.19

137.63

47.60

57.21

5'

7.89

5

16.84

10

14.60

19

4

15

24.66

3

13 14

42.67

1 2

12

132.20

20

168

160

152

144

136

128

120

112

104

88 96 Chemical Shift (ppm)

80

72

64

56

48

18.18

46.71

133.89

176

30.66 32.85 33.74 35.40

140.75

178.65

Chloroform-d

40

32

24

16

8

44