C. Meier et al.
[D6]DMSO): d=8.56 (s, 1H), 7.49–7.47 (m, 2H), 7.40–7.30 (m, 3H), 7.07
(d, J=8.4 Hz, 2H), 6.80 (d, J=8.0 Hz, 2H), 6.30 (dd, J=6.9 Hz, 1H),
6.01 (s, 2H), 5.47 (s, 2H), 4.62 (ddd, J=6.1, 3.0, 3.0 Hz, 1H), 3.82–3.78
(m, 2H), 3.68 (dd, J=10.2, 4.5 Hz, 1H), 3.42–3.38 (m, 1H), 2.22 (s, 3H),
2.11–2.09 (m, 1H), 0.89 (s, 9H), 0.80 (s, 9H), 0.11 (s, 6H), ꢀ0.02 (s, 3H),
ꢀ0.03 ppm (s, 3H); 13C NMR (101 MHz, [D6]DMSO): d=157.6, 157.4,
146.4, 138.1, 137.0, 129.9, 129.2, 128.4, 128.3, 127.9, 123.9, 117.4, 111.0,
87.1, 83.0, 72.7, 66.4, 63.0, 36.5, 25.7, 20.3, 18.0, ꢀ4.6, ꢀ5.2 ppm; IR
124.3, 120.1, 119.0, 116.8, 114.4, 111.3, 87.2, 83.0, 72.7, 66.5, 63.0, 57.9,
36.5, 25.7, 17.9, ꢀ4.7, ꢀ5.4 ppm; IR (KBr): n˜ =3495, 3357, 2952, 2927,
1597, 1560, 1456, 1416, 1254, 835, 778 cmꢀ1; MS (HRFAB): m/z: calcd
for: 764.3902, found 765.3974 [M+H+].
General procedure II for the debenzylation of O6-benzyl-8N-arylamino-
3’,5’-bis(tert-butyldimethylsilyl)-2’-deoxyguanosine derivatives:
A dried
flask was purged with nitrogen and then charged with the O6-benzyl-8N-
arylamino-3’,5’-bis(tert-butyldimethylsilyl)-2’-deoxyguanosine derivative
and Pd/C. Dry methanol was added and the reaction mixture was stirred
under a hydrogen atmosphere at room temperature for 1–48 h. The reac-
tion mixture was centrifuged several times with methanol, filtered, and
concentrated in vacuo to give the pure product.
(KBr): n˜ =3465, 3348, 2953, 1600, 1409, 1257, 1105, 1060, 835, 698 cmꢀ1
MS (HRFAB): m/z: calcd for: 690.3745, found 691.3809 [M+H+].
;
O6-Benzyl-8N-(4-methoxyphenylamino)-3’,5’-bis(tert-butyldimethylsilyl)-
2’-deoxyguanosine (12c): GP I was conducted with 3.02 g (4.54 mmol) of
bromide 11 (reaction time 70 h), which afforded a yellow foam (2.00 g,
62%). M.p. 117–1218C; [a]25406 =+158 (c=0.1, CHCl3); 1H NMR
(400 MHz, [D6]DMSO): d=8.47 (s, 1H), 7.51 (d, J=9.0 Hz, 2H), 7.47 (d,
J=7.2 Hz, 2H), 7.38 (dd, J=7.2 Hz, 3H), 6.88 (d, J=9.0 Hz, 2H), 6.29
(dd, J=6.9 Hz, 1H), 5.97 (s, 2H), 5.46 (s, 2H), 4.63 (ddd, J=6.2, 3.1,
3.1 Hz, 1H), 3.84 (ddd, J=13.2, 9.6, 5.5 Hz, 2H), 3.70 (s, 3H), 3.68 (dd,
J=13.2, 5.5 Hz, 1H), 3.43 (ddd, J=13.3, 6.7 Hz, 1H), 2.10 (ddd, J=13.3,
6.7, 3.2 Hz, 1H), 0.90 (s, 9H), 0.81 (s, 9H), 0.12 (s, 6H), ꢀ0.02 (s, 3H),
ꢀ0.03 ppm (s, 3H); 13C NMR (101 MHz, [D6]DMSO): d=157.6, 157.4,
147.2, 139.1, 137.3, 133.9, 128.6, 128.5, 128.1, 120.0, 114.0, 87.3, 83.0, 72.9,
66.6, 63.2, 55.3, 36.6, 25.9, 18.0, ꢀ5.2 ppm; IR (KBr): n˜ =3332, 2952, 2929,
1633, 1605, 1565, 1414, 1256, 835 cmꢀ1; MS (HRFAB): m/z: calcd for:
706.3718, found 707.3622 [M+H+].
8N-(Phenylamino)-3’,5’-bis(tert-butyldimethylsilyl)-2’-deoxyguanosine
(13a): GP II was conducted with 12a (1.90 g, 2.80 mmol; reaction time
20
546
24 h), which afforded a white solid (1.48 g, 90%). M.p. 1558C; [a]
=
ꢀ10.88 (c=0.8, CHCl3); 1H NMR (400 MHz, [D6]DMSO): d=10.52 (s,
1H), 8.35 (s, 1H), 7.45 (dd, J=7.6 Hz, 2H), 7.23 (dd, J=8.5 Hz, 2H),
6.87 (dd, J=7.3, 7.3 Hz, 1H), 6.22 (dd, J=7.1 Hz, 1H), 6.19 (s, 2H), 4.53
(ddd, J=3.1, 3.1, 6.2 Hz, 1H), 3.84–3.78 (m, 2H), 3.71 (ddd, J=8.2, 8.2,
8.1 Hz, 1H), 3.23–3.16 (m, 1H), 2.18–2.14 (m, 1H), 0.88 (s, 9H), 0.83 (s,
9H), 0.10 (s, 6H), 0.00 ppm (s, 6H); 13C NMR (101 MHz, [D6]DMSO):
d=155.3, 152.0, 149.5, 143.2, 141.3, 128.2, 120.0, 116.5, 113.0, 86.8, 82.5,
72.3, 62.7, 36.5, 25.4, 25.3, 17.7, 17.4, ꢀ5.1, ꢀ5.3 ppm; IR (KBr): n˜ =3353,
1179, 1006, 953, 692, 667, 576, 501 cmꢀ1; MS (HRFAB): m/z: calcd for:
586.8736, found 587.8705 [M+H+].
O6-Benzyl-8N-(3,5-dimethylphenylamino)-3’,5’-bis(tert-butyldimethylsil-
yl)-2’-deoxyguanosine (12d): GP I was conducted with 2.50 g (3.76 mmol)
8N-(4-Methylphenylamino)-3’,5’-bis(tert-butyldimethylsilyl)-2’-deoxygua-
nosine (13b): GP II was conducted with 12b (1.90 g, 2.74 mmol; reaction
of bromide 11 (reaction time 72 h), which afforded an orange solid
time 24 h), which afforded a yellow solid (1.69 g, 85%). M.p. 1198C;
20
(1.74 g, 66%). M.p. 1358C; [a] =+158 (c=1.64, CHCl3); 1H NMR
20
[a] =ꢀ7.98 (c=0.47, CHCl3); 1H NMR (400 MHz, [D6]DMSO): d=
546
546
(400 MHz, [D6]DMSO): d=8.38 (s, 1H), 7.46 (d, J=7.2 Hz, 2H), 7.36 (t,
J=7.5 Hz, 2H), 7.32–7.29 (dd, J=7.2, 8.2 Hz, 2H), 7.25 (d, J=7.1 Hz,
1H), 6.55 (s, 1H), 6.26 (t, J=6.9 Hz, 1H), 6.02 (s, 2H), 5.49 (s, 2H),
4.61–4.59 (m, 1H), 3.85–3.79 (m, 2H), 3.67 (dd, J=4.6, 5.8 Hz, 1H), 2.20
(s, 6H), 2.11–2.08 (m, 2H), 0.88 (s, 9H), 0.80 (s, 9H), 0.10 (s, 6H),
0.00 ppm (s, 6H); 13C NMR (101 MHz, [D6]DMSO): d=157.8, 154.9,
154.1, 149.3, 141.0, 137.7, 128.7, 128.5, 128.4, 128.3, 128.0, 120.8, 117.9,
87.2, 84.0, 72.8, 66.6, 63.2, 36.7, 25.9, 21.4, 17.4, 16.7, ꢀ5.2, ꢀ5.4,
ꢀ6.0 ppm; IR (KBr): n˜ =3377, 3333, 2950, 2857, 1616, 1565, 1464, 1413,
1253, 1108, 833, 783 cmꢀ1; MS (HRFAB): m/z: calcd for: 704.3902, found
705.3993 [M+H+].
10.55 (s, 1H), 8.22 (s, 1H), 7.37 (d, J=8.4 Hz, 2H), 7.04 (d, J=8.4 Hz,
2H), 6.20 (dd, J=7.0 Hz, 1H), 6.17 (s, 2H), 4.55–4.52 (m, 1H), 3.84–3.81
(ddd, J=8.3, 9.3 Hz, 2H), 3.73–3.70 (m, 1H), 3.18 (ddd, J=13.2, 7.0,
6.7 Hz, 1H), 2.23 (s, 3H), 2.06 (ddd, J=13.2, 6.7, 3.0 Hz, 1H), 0.88 (s,
9H), 0.83 (s, 9H), 0.09 (s, 6H), 0.02 (s, 3H), 0.00 ppm (s, 3H); 13C NMR
(101 MHz, [D6]DMSO): d=155.7, 152.3, 146.0, 143.9, 139.0, 128.3, 123.9,
114.5, 111.0, 87.1, 82.9, 72.7, 63.1, 36.9, 25.7, 20.1, 18.1, ꢀ4.6, ꢀ5.3 ppm;
IR (KBr): n˜ =3312, 2918, 1693, 1603, 1517, 1369, 1252, 1083, 837,
776 cmꢀ1
[M+H+].
; MS (HRFAB): m/z: calcd for: 600.3276, found 601.3344
8N-(4-Methoxyphenylamino)-3’,5’-bis(tert-butyldimethylsilyl)-2’-deoxy-
guanosine (13c): GP II was conducted with 12c (1.92 g, 2.69 mmol; reac-
tion time 4 h), which afforded a white solid (1.58 g, 96%). M.p. 1128C;
[a]25046 =ꢀ9.98 (c=0.8, CHCl3); 1H NMR (400 MHz, [D6]DMSO): d=
10.53 (s, 1H), 8.14 (s, 1H), 7.42 (d, J=9.0 Hz, 2H), 6.84 (d, J=9.0 Hz,
2H), 6.20 (dd, J=7.1 Hz, 1H), 6.15 (s, 2H), 4.52 (ddd, J=6.2, 3.1, 3.1 Hz,
1H), 3.85–3.83 (m, J=13.2, 9.6, 5.5 Hz, 2H), 3.70 (s, 3H), 3.68 (dd, J=
13.2, 5.5 Hz, 1H), 3.20 (ddd, J=13.8, 6.6 Hz, 1H), 2.10 (ddd, J=13.8, 6.6,
3.2 Hz, 1H), 0.88 (s, 9H), 0.83 (s, 9H), 0.10 (s, 6H), 0.00 (s, 3H),
ꢀ0.03 ppm (s, 3H); 13C NMR (101 MHz, [D6]DMSO): d=155.8, 153.9,
152.2, 150.0, 144.7, 134.8, 128.4, 119.3, 114.0, 87.3, 83.0, 72.9, 63.3, 55.3,
37.0, 26.0, 25.9, 18.0, 17.9, ꢀ4.6, ꢀ5.2 ppm; IR (KBr): n˜ =2929, 2856,
1698, 1613, 1513, 1248, 1108, 834, 777 cmꢀ1; MS (HRFAB): m/z: calcd
616.3222, found 617.3312 [M+H+].
O6-Benzyl-8N-(4-biphenylamino)-3’,5’-bis(tert-butyldimethylsilyl)-2’-de-
oxyguanosine (12e): GP I was conducted with bromide 11 (1.40 g,
1.56 mmol, reaction time 55 h), which afforded
a light-yellow foam
(1.03 g, 65%). M.p. 1468C; [a] =+16.38 (c=0.32, CHCl3); 1H NMR
20
546
(400 MHz, [D6]DMSO): d=8.05 (s, 1H), 7.52–7.20 (m, 14H), 6.50 (s,
2H), 6.20 (dd, J=6.8, 7.4 Hz, 1H), 5.48 (s, 2H), 4.51 (ddd, J=6.7, 4.3,
4.3 Hz, 1H), 3.81 (dd, J=10.6, 5.0 Hz, 1H), 3.73 (ddd, J=5.0, 4.3, 6.0 Hz,
1H), 3.69 (dd, J=10.6, 6.0 Hz, 1H), 3.63 (ddd, J=13.0, 6.2, 6.8 Hz, 1H),
2.26 (ddd, J=13.0, 4.3, 7.4 Hz, 1H), 0.89 (s, 9H), 0.85 (s, 9H), 0.10 (s,
3H), 0.09 (s, 3H), ꢀ0.04 (s, 3H), ꢀ0.05 ppm (s, 3H); 13C NMR
(101 MHz, [D6]DMSO): d=160.2, 159.9, 154.3, 148.5, 140.9, 137.8, 136.8,
128.9, 128.6, 128.4, 128.2, 127.5, 127.4, 127.2, 125.8, 125.5, 114.4, 82.5,
72.4, 72.3, 67.0, 62.9, 37.2, 26.0, 25.9, 18.1, 17.9, ꢀ4.5, ꢀ4.7, ꢀ5.2,
ꢀ5.3 ppm; IR (KBr): n˜ =2940, 2908, 2877, 1607, 1559, 1423, 1159, 1005,
938, 785 cmꢀ1; MS (HRFAB): m/z: calcd for: 752.3902, found 753.3992
[M+H+].
8N-(3,5-Dimethylphenylamino)-3’,5’-bis(tert-butyldimethylsilyl)-2’-deoxy-
guanosine (13d): GP II was conducted with of 12d (1.17 g, 1.54 mmol; re-
action time 12 h), which afforded a white solid (739 mg, 78%). M.p.
20
1858C; [a] =ꢀ438 (c=0.8, CHCl3); 1H NMR (400 MHz, [D6]DMSO):
O6-Benzyl-8N-(2-aminofluorenyl)-3’,5’-bis(tert-butyldimethylsilyl)-2’-de-
oxyguanosine (12e): GP I was conducted with bromide 11 (1.95 g,
546
d=10.57 (s, 1H), 8.04 (s, 1H), 7.31–7.28 (m, 2H), 6.97 (s, 1H), 6.51 (s,
2H), 6.20–6.11 (m, 1H), 4.49 (t, J=2.8 Hz, 1H), 4.02 (q, J=7.1 Hz, 1H),
3.82–3.57 (m, 2H), 3.08 (q, J=6.8 Hz, 1H), 2.23–2.19 (m, 1H), 0.86 (s,
9H), 0.83 (s, 9H), 0.7 (s, 6H), 0.00 ppm (s, 6H); 13C NMR (101 MHz,
[D6]DMSO): d=155.9, 152.7, 150.2, 143.6, 142.0, 137.7, 119.7, 117.8,
112.2, 93.7, 87.2, 73.0, 63.2, 37.2, 30.5, 26.0, 26.0, 21.4, 18.3, 17.3, ꢀ4.7,
ꢀ6.1 ppm; IR (KBr): n˜ =3489, 2928, 2857, 1696, 1596, 1497, 1406, 1285,
1091, 836, 775 cmꢀ1; MS (HRFAB): m/z: calcd for: 614.3439, found
615.3510 [M+H+].
2.91 mmol; reaction time 78 h), which afforded a yellow solid (2.05 g,
20
91%). M.p. 858C; [a] =ꢀ5.28 (c=0.5, CHCl3); 1H NMR (400 MHz,
546
[D6]DMSO): d=8.77 (s, 1H), 7.91–7.88 (m, 1H), 7.76 (dt, J=7.8, 5.9 Hz,
1H), 7.59 (dd, J=8.3, 1.9 Hz, 1H), 7.52–7.46 (m, 3H), 7.42–7.20 (m, 5H),
7.11–7.07 (m, 1H), 6.34 (dd, J=6.9 Hz, 1H), 6.07 (s, 2H), 5.50 (s, 2H),
4.63 (ddd, J=6.1, 3.1 Hz, 1H), 3.92 (s, 2H), 3.89–3.86 (m, 2H), 3.71–3.69
(m, 1H), 3.43 (ddd, J=10.1, 6.5 Hz, 1H), 2.13 (ddd, J=10.1, 7.2, 3.5 Hz,
1H), 0.90 (s, 9H), 0.81 (s, 9H), 0.12 (s, 6H), ꢀ0.00 (s, 3H), ꢀ0.01 ppm (s,
3H); 13C NMR (101 MHz, [D6]DMSO): d=157.8, 157.6, 153.9, 146.1,
143.8, 142.5, 141.3, 140.1, 137.0, 134.5, 128.4, 128.4, 127.9, 126.7, 124.9,
8N-(4-Biphenylamino)-3’,5’-bis(tert-butyldimethylsilyl)-2’-deoxyguanosine
(13e): GP II was conducted with 12e (1.00 g, 1.32 mmol; reaction time
11202
ꢁ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2008, 14, 11194 – 11208