General Remarks. All chemicals were obtained from commercial sources and were of ACS reagent grade or higher and were used without further purification.
Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is © The Royal Society of Chemistry 2011
Supporting Information Synthesis and Oligomerization of Fmoc/Boc-Protected PNA Monomers of 2,6-Diaminopurine, 2-Aminopurine and Thymine André St. Amant and Robert H.E. Hudson* Department of Chemistry, The University of Western Ontario, London, Ontario, Canada, N6A 5B7
S1
Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is © The Royal Society of Chemistry 2011
Table of Contents S2.
Table of Contents
S3.
General Remarks & mass spec of PNA1 & PNA2
S4.
1
S5.
1
S6.
1
S7.
1
S8.
1
S9.
1
S10.
1
S11.
1
S12.
1
S13.
1
S14.
1
S15.
1
S16.
1
S17.
1
S18.
HPLC chromatogram trace PNA1
S19.
HPLC chromatogram trace PNA2
H NMR of 1 & 1H NMR of 1 H NMR of 2 & 13C NMR of 2 H NMR of 3 & 13C NMR of 3 H NMR of 4 & 13C NMR of 4 H NMR of 5 & 13C NMR of 5 H NMR of 6 & 13C NMR of 6 H NMR of 7 & 13C NMR of 7 H NMR of 8 & 13C NMR of 8 H NMR of 9 & 13C NMR of 9 H NMR of 10 & 13C NMR of 10 H NMR of 11a & 13C NMR of 11a H NMR of 12 & 13C NMR of 12 H NMR of 13 & 13C NMR of 13 H NMR of 14 & 13C NMR of 14
S2
Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is © The Royal Society of Chemistry 2011
General Remarks. All chemicals were obtained from commercial sources and were of ACS reagent grade or higher and were used without further purification. Solvents for solution-phase chemistry were dried by passing through activated alumina columns. Flash column chromatography (FCC) was performed on Merck Kieselgel 60, 230-400 mesh. Thin layer chromatography (TLC) was performed on Merck Kieselgel 60 TLC plates. Chemical shifts are reported in parts per million (δ), were measured from Tetramethylsilane (0 ppm) and are referenced to the solvent CDCl3 (7.26 ppm), DMSO-d6 (2.49 ppm), D2O (4.79 ppm) for 1H NMR and CDCl3 (77.0 ppm), DMSO-d6 (39.5 ppm) for 13C NMR. Multiplicities are described as s (singlet), d (doublet), t (triplet), q (quartet), m (multiplet) and br s (broad singlet). Coupling constants (J) are reported in Hertz (Hz). Resonances due to restricted rotation around the amide bond (rotamers) are reported as major (ma.) and minor (mi.). High resolution mass spectra (HRMS) were obtained using electron impact (EI) or electrospray ionization (ESI).
PNA1. HRMS (ESI) calculated for C155H204N74O47: [M + 3H+] 1285.5361, Found 1285.8582; [M + 4H+] 964.404, Found 964.6530. PNA2. HRMS (ESI) calculated for C125H161N67O35: [M + 3H+] 1054.4371, Found 1054.7417; [M + 4H+] 791.0798, Found 791.3110.
S3
Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is © The Royal Society of Chemistry 2011
H NMR (400 MHz, CDCl3) of 1 1.59
1
PROTON.esp 1.0 0.9 0.8
0.6 0.5
0.1 0
1.58
7.36 7.35 7.25 6.91
0.2
5.00 0.97 14
13
1.92
Chloroform-d 0.3
4.47
0.4
5.20
Normalized Intensity
0.7
13
12
11
10
9
8
2.01 2.00
7 6 5 Chemical Shift (ppm)
3.13 10.41 4
3
2
1
0
-1
-2
C NMR (101 MHz, CDCl3) of 1 M09(s)
CARBON01.esp
M10(s) M11(s) M12(s)
27.19
128.45
M02(s)
128.44 128.19
86.57
M07(s)
M03(s) M04(s)
110.47
67.52
M08(s)
77.32 76.69
134.55
0.25
12.06
M01(s)
48.55
139.65
0.50
148.78 147.58
M15(s) M13(s) M16(s) M14(s) M17(s)
0.75
167.06 161.36
Normalized Intensity
1.00
0 220
200
180
160
140
120 100 Chemical Shift (ppm)
S4
80
60
40
20
0
-20
Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is © The Royal Society of Chemistry 2011
1
H NMR (400 MHz, DMSO-d6) of 2 PROTON.esp
1.49
DMSO-d6
1.0 0.9
0.7 0.6 0.5
1.79
Normalized Intensity
0.8
3.16
0.4
7.64
0.2
2.49
4.41
0.3
0.1 0
1.00 14
13
13
12
11
10
9
8
1.93 7 6 5 Chemical Shift (ppm)
2.85 9.08 4
3
2
1
0
-1
-2
C NMR (101 MHz, DMSO-d6) of 2 CARBON01.esp M09(s)
M02(s)
39.72 39.30
1.0 0.9 0.8
39.92 39.09
0.6 M12(s)
0.5
M13(s) M14(s)
27.75
11.96
40.13
142.00
48.69 49.13
0.1
M10(s)
108.38
0.2
151.09
0.3
M01(s)
M11(s)
M15(s)
141.82
0.4
169.84 164.50
Normalized Intensity
0.7
0 220
200
180
160
140
120 100 Chemical Shift (ppm)
S5
80
60
40
20
0
-20
Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is © The Royal Society of Chemistry 2011
H NMR (400 MHz, DMSO-d6) of 3 3.33
1
Proton.esp 1.0 0.9 0.8
DMSO-d6
1.46
0.6 0.5
0
1.98
1.41 1.18 1.16 1.14
0.1
3.43 3.26 3.25
7.88 7.86 7.67 7.65 7.39
0.2
5.20 5.12 4.75 4.33 4.31 4.13
7.35
0.3
2.01 1.95 10.79 0.62 1.41 1.28 0.62 5.30 1.60 1.61 0.94 3.04 8.72 14
13
12
11
10
9
8
7 6 5 Chemical Shift (ppm)
4
3
2
1
0
-1
-2
C NMR (101 MHz, CDCl3) of 3 128.23
13
2.49 2.49 1.78 1.48
0.4
7.34 7.32 7.30 7.28
Normalized Intensity
0.7
26.97
Carbon.esp
1.0 0.9
127.77
86.22
Chloroform-d
11.86 20.59 13.80
66.82 67.43 66.39 66.25 59.95
86.32
109.67 109.47
77.32 77.00 76.68
128.34 127.38 119.58
128.44
0.1
140.49
0.2
148.64 147.74
0.3
161.32
168.97
0.4
161.41
0.5
134.71
143.40 140.79
0.6
48.53 46.74 38.77 27.55
0.7
170.74 166.88
Normalized Intensity
0.8
0 220
200
180
160
140
120 100 Chemical Shift (ppm)
S6
80
60
40
20
0
-20
Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is © The Royal Society of Chemistry 2011
1
H NMR (400 MHz, DMSO-d6) of 4 2101.esp
1.48
DMSO-d6
0.9
2.72 2.49
0.7 0.6
2.49
Normalized Intensity
0.8
1.45
2.88
1.0
0.5
0.2
3.16
0.3
4.52 4.22 3.95
7.94 7.88 7.86 7.66 7.40 7.31
1.77
0.4
0.1 0
0.64 1.92 1.81 0.56 1.03 4.51 0.75 0.86 0.95 1.75 1.59 7.58 1.98 1.94 2.98 0.05 8.45 14
12
11
10
9
8
7 6 5 Chemical Shift (ppm)
4
3
2
1
0
-1
-2
C NMR (151 MHz, CDCl3) of 4 39.64 39.51 39.37
13
13
CARBON_01
1.0 0.9
39.78 39.23
11.97
27.08
46.87 47.89
65.65
108.26
86.16
0.2
148.10
0.3
156.47
170.99 170.60 167.36 164.54
0.4
125.22
151.12
0.5
127.72
143.94
0.6
31.37
140.84
0.7
Normalized Intensity
120.16
0.8
0.1 0
220
200
180
160
140
120 100 Chemical Shift (ppm)
S7
80
60
40
20
0
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Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is © The Royal Society of Chemistry 2011
H NMR (400 MHz, CDCl3) of 5 1.43 1.41
1
1901.esp 1.0 0.9 0.8
0.6
1.68
Normalized Intensity
0.7
0.5 0.4 0.3 Chloroform-d
7.25
0.2 0.1 0
1.00 14
12
11
10
9
8
7 6 5 Chemical Shift (ppm)
4
3
2
1
0
-1
-2
C NMR (101 MHz, CDCl3) of 5 27.71
13
13
9.36 37.35
CARBON01.ESP
27.57
1.0 0.9
27.81
0.7 0.6
0.89
41.93
0.1
87.26
0.2
127.82
0.3
150.59 149.69 145.54 143.83
0.4
77.32 77.00 76.69
83.87 83.22
0.5
153.70 152.86
Normalized Intensity
0.8
0 220
200
180
160
140
120 100 Chemical Shift (ppm)
S8
80
60
40
20
0
-20
Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is © The Royal Society of Chemistry 2011
H NMR (400 MHz, DMSO-d6) of 6 1.42
1
0803.esp
1.40
1.0
1.44
0.9 0.8
1.56
0.6 0.5
1.19
Chloroform-d
7.25
1.15 1.13 1.13 1.11
0.05
1.59 1.66 1.65 1.64 1.63
8.35
11.22 11.22
0.1
3.72 3.70 3.49 3.44
8.33
0.3 0.2
1.18
0.4
3.47 3.46
Normalized Intensity
0.7
0 0.70 14
12
11
10
9
8
39.96 7 6 5 Chemical Shift (ppm)
4
3
2
1
0
-1
C NMR (101 MHz, CDCl3) of 6 27.74
13
13
1.00
27.58
CARBON01.ESP
1.0 0.9
0.7 0.6 0.5
0.1
27.80
84.30
0.2
109.92
150.80 149.87 145.34
0.3
83.39 77.21 77.00 76.79
0.4
151.40
Normalized Intensity
0.8
0 220
200
180
160
140
120 100 Chemical Shift (ppm)
S9
80
60
40
20
0
-20
-2
Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is © The Royal Society of Chemistry 2011
H NMR (400 MHz, DMSO-d6) of 7 1.40 1.39
1
PROTON.esp 1.0 0.9 0.8
0.6 0.5 0.4 0.3
Chloroform-d
8.14 7.38 7.37 7.36 7.25
0.2 0.1 0
0.91 6.18 14
13
12
11
10
9
8
2.00 1.92
7 6 5 Chemical Shift (ppm)
36.82 4
3
2
1
0
-1
C NMR (101 MHz, CDCl3) of 7 27.67
13
5.21 5.05
Normalized Intensity
0.7
27.56
CARBON_01.ESP
1.0 0.9
0.7 0.6 0.5
27.76
52.89 44.27 44.14
83.68 83.18 77.32 77.00 76.68 67.94
128.67 128.44 126.74
0.1
167.00
0.2
154.19
0.3
150.64 149.81 145.78
0.4
175.97
Normalized Intensity
0.8
0 220
200
180
160
140
120 100 Chemical Shift (ppm)
S10
80
60
40
20
0
-20
-2
Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is © The Royal Society of Chemistry 2011
1
H NMR (400 MHz, DMSO-d6) of 8 PROTON.esp
1.33
DMSO-d6
1.0
1.35
0.9
Normalized Intensity
0.8 0.7 0.6 0.5 0.4
5.05
1.04
2.00
0.1 0
14
12
11
10
9
8
7 6 5 Chemical Shift (ppm)
35.94 4
3
2
1
0
C NMR (101 MHz, MeOD-d4) of 8 28.02
13
13
3.40 3.38
8.63
0.2
2.49 1.40 1.40 1.37 1.27 1.26 1.26 1.25
0.3
CARBON_01.ESP
1.0
49.15 48.94 48.72
0.9 0.8
85.37
0.2 0.1
31.08
0.3
128.12
0.4
49.58 48.30
0.5
49.36 48.51
84.89
0.6
155.90 152.96 152.16 151.31 149.74
Normalized Intensity
0.7
0
220
200
180
160
140
120 100 Chemical Shift (ppm)
S11
80
60
40
20
0
-1
-2
Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is © The Royal Society of Chemistry 2011
H NMR (400 MHz, DMSO-d6) of 9 1.35
1
PROTON 1.0 0.9
1.30
0.8
3.34 2.50
0.6
2.50
0.5
7.34 7.86 7.67
8.50 8.49
0.1
5.43 5.24 5.11 4.51 4.36 4.17
0.2
2.37
0.3
2.51
0.4
3.56 3.20
Normalized Intensity
0.7
0 1.05 1.99 2.30 13.97 1.29 1.87 1.88 0.90 5.38 1.33 2.55 2.25 51.40 14
12
11
10
9
8
7 6 5 Chemical Shift (ppm)
4
3
2
1
0
-1
-2
C NMR (101 MHz, CDCl3) of 9 28.02
13
13
CARBON.esp
1.0
27.90
0.9
0.7 0.6
128.89 128.49
0.5
14.35
22.86
31.80
49.37 49.15 47.44
83.98 83.56 67.60 66.74
0.1
84.01
0.2
Chloroform-d
120.25
0.3
144.04 143.85 141.50 129.06 128.02
151.11 150.19
0.4
154.56 152.18
Normalized Intensity
0.8
0 220
200
180
160
140
120 100 Chemical Shift (ppm)
S12
80
60
40
20
0
-20
Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is © The Royal Society of Chemistry 2011
H NMR (400 MHz, acetone-d6) of 10 3.30
1
PROTON_01.esp 1.0
1.40
1.41
0.9
1.39
0.8
1.38
0.6
2.04
0.5 0.4
2.03
Normalized Intensity
0.7
2.05 2.03
0.3
8.36 7.85 7.84 7.82 7.69 7.67 7.40 7.38 7.32 7.30 5.43 5.30 4.44 4.42 4.32 4.30 4.18 3.74
0.2 0.1 0
0.94 1.98 1.95 3.89 0.38 0.27 0.93 0.77 1.69 0.81 0.93 1.05 1.04 1.82 0.73 35.99 14
12
11
10
9
8
7 6 5 Chemical Shift (ppm)
4
3
2
1
0
-1
-2
C NMR (101 MHz, acetone-d6) of 10 CARBON01.ESP
206.26
13
13
1.0 0.9
0.6
27.91 29.72
29.92 30.11
0.7
30.30
0.5 0.4
48.15 45.35 39.95 30.49
67.01
0.1
84.01 83.50
0.2
127.98 120.87
0.3
171.00 167.88 167.26 157.53 155.78 152.79 151.74 151.00 148.95 145.10 142.14 128.57
Normalized Intensity
0.8
0 220
200
180
160
140
120 100 Chemical Shift (ppm)
S13
80
60
40
20
0
-20
Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is © The Royal Society of Chemistry 2011
H NMR (400 MHz, CDCl3) of 11a 1.42
1
1001.esp 1.0 0.9 0.8
0.6 0.5 0.4 0.3
Chloroform-d
8.19 7.37 7.37 7.35 7.25
0.1 0
1.00 14
13
12
11
10
9
5.18
8
2.15 2.07
7 6 5 Chemical Shift (ppm)
19.20 4
3
2
1
0
-1
C NMR (101 MHz, CDCl3) of 11a 27.68
13
5.22 5.05
0.2
1.58
Normalized Intensity
0.7
CARBON_01.ESP
1.0 0.9
0.7
128.64
0.6 0.5
0.1
44.45
77.00 76.68
68.05
83.59
134.24 129.42 128.77 128.47
0.2
152.70
0.3
146.42
150.31
0.4
166.16
Normalized Intensity
0.8
0 220
200
180
160
140
120 100 Chemical Shift (ppm)
S14
80
60
40
20
0
-20
-2
Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is © The Royal Society of Chemistry 2011
H NMR (400 MHz, MeOH-d4) of 12 1.38
1
PROTON_01.esp 1.0 0.9 0.8
Normalized Intensity
0.7 0.6 0.5 0.4
0
0.87 0.91 14
12
11
10
9
2.00 8
18.60
7 6 5 Chemical Shift (ppm)
4
3
2
1
0
-1
C NMR (101 MHz, MeOH-d4) of 12 28.15
13
13
1.40
9.10 0.1
8.57
0.2
3.31
5.49 5.17 4.90
0.3
CARBON_01.esp
1.0 0.9
84.98
0.8
48.94
0.6
49.78 49.57 49.36 48.72 48.51 45.35
0.5
152.24 149.76
0.4
0.1
133.33
0.2
154.39 153.93
0.3 170.01
Normalized Intensity
0.7
0 220
200
180
160
140
120 100 Chemical Shift (ppm)
S15
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Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is © The Royal Society of Chemistry 2011
H NMR (400 MHz, CDCl3) of 13 1.43
1
PROTON_01.esp 1.0
7.27
0.9 0.8
Normalized Intensity
0.7 0.6 0.5 0.4 0.3
0
1.58
0.96 0.33 0.84 2.63 2.54 8.90 0.60 1.83 1.19 0.54 1.19 0.84 0.43 1.02 1.25 1.13 0.56 0.38 1.72 0.53 0.65 17.26 14
13
12
11
10
9
8
7 6 5 Chemical Shift (ppm)
4
3
2
1
0
-1
C NMR (101 MHz, CDCl3) of 13 27.77
13
5.76 5.25 5.19 4.99 4.93 4.49 4.47 4.41 4.39 4.08 4.07 3.63 3.48 2.79
0.1
8.05 7.73 7.71 7.58 7.39 7.37
9.11
0.2
CARBON_01
1.0 0.9
0.7 0.6
29.61 27.27
49.19 47.14
0.1
67.39
0.2
141.21
0.3
83.30
0.4
128.78 128.22 127.73 127.66 127.01 119.96 109.92
128.61
77.32 76.69
0.5
169.26 156.57 152.70 150.95 149.25
Normalized Intensity
0.8
0 220
200
180
160
140
120 100 Chemical Shift (ppm)
S16
80
60
40
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-20
-2
Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is © The Royal Society of Chemistry 2011
H NMR (400 MHz, CDCl3) of 14 1.43
1
PROTON_01.esp
1.40
1.0 0.9 0.8
0.6 0.5
0.1 0
1.00 0.56 0.37 2.38 2.44 5.22 0.39 0.26 0.12 0.50 0.99 0.96 3.73 1.01 0.83 1.35 1.35 1.63 20.61 14
13
12
11
10
9
8
7 6 5 Chemical Shift (ppm)
4
3
2
1
0
-1
-2
C NMR (101 MHz, CDCl3) of 14 27.79
13
8.28 8.10
9.12 9.09
0.2
2.77
0.3
1.37
0.4
7.73 7.71 7.33 7.27 7.25 7.24 7.23 7.17 6.83 6.05 5.30 4.85 4.21 4.19 4.17 4.01 3.54 3.36
Normalized Intensity
0.7
CARBON_01
1.0 0.9
77.51 77.19 76.87
0.8
0.6 0.5
27.35
39.30
50.60 48.91 47.08
0.1
66.71
0.2
156.89 152.69 150.96 148.92 143.64 141.17 131.38 127.73 127.07 119.95
0.3
83.57
0.4
171.56
Normalized Intensity
0.7
0 220
200
180
160
140
120 100 Chemical Shift (ppm)
S17
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60
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20
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Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is © The Royal Society of Chemistry 2011
HPLC trace of crude PNA1
UPLC trace of purified PNA1
S18
Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is © The Royal Society of Chemistry 2011
HPLC trace of crude PNA2
UPLC trace of purified PNA2
S19
