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HELVETICA CHIMICA ACTA – Vol. 88 (2005)
5.22 (d, J=4.7, 1 H; OCH2O); 6.03 (d, J=6.2, HꢀC(1’)); 6.80–6.82 (d, J=9.4, 4 arom. H); 7.22–7.44 (m, 9 arom.
H). 13C NMR (100 MHz, CDCl3): 12.3 (d, Me2CH); 18.2 (q, Me2CH); 31.5 (t, C(5)); 36.8 (t, C(6)); 55.7 (q, MeO);
63.9 (t, C(5’)); 71.4 (d, C(3’)); 79.8 (d, C(2’)); 83.2 (d, C(4’)); 86.9 (s, arom. C); 87.1 (d, C(1’)); 90.9 (t, OCH2O);
113.6 (d, arom. C); 127.4, 128.3, 128.6, 128.7, 130.5 (5d, arom. C); 135.9, 136.0 (2s, arom. C); 144.9 (s, arom. C);
152.5 159.0 (2s, C(2), C(4)); 169.9 (s, arom. C). ESI-MS: 757.38 (100, [M+H]+).
5’-O-(4,4’-Dimethoxytrityl)-2’-O-{[(triisopropylsilyl)oxy]methyl}inosine (17). A soln. of 16 (1.0 g, 1.9 mmol,
prepared according to [24]) in MeOH (2 ml) was treated with a sat. NH3 soln. in MeOH (6 ml) and stirred for 3 h
at r.t. After evaporation, the residue was dissolved in pyridine (5.5 ml), treated with (MeO)2TrCl (0.78 g, 2.3
mmol), and stirred for 2 h at r.t. Workup and CC (SiO2 (25 g), hexane/AcOEt 1:1, then CH2Cl2/MeOH 99 :1
! 9 :1) gave 17 (939 mg, 67%). Yellow foam. TLC (CH2Cl2/MeOH 1:9): Rf 0.50. 1H-NMR (400 MHz,
i
CDCl3) 0.90–1.10 (m, Pr3Si); 3.10 (d, J=3.1, OHꢀC(3’)); 3.42 (dd, J=3.9, 10.2, HꢀC(5’)); 3.47 (dd, J=3.9,
10.2, H’ꢀC(5’)); 3.80 (s, 2 MeO); 4.32 (m, HꢀC(4’)); 4.55 (m, HꢀC(3’)); 4.84 (t, J=4.7, HꢀC(2’)); 4.98 (d,
J=4.7, 1 H, OCH2O); 5.17 (d, J=4.7, 1 H OCH2O); 6.17 (d, J=5.4, HꢀC(1’)); 6.82 (d, J=8.8, 4 arom. H);
7.30–7.46 (m, 9 arom. H); 7.81 (s, HꢀC(8)); 7.94 (s, HꢀC(2)); 12.98 (br. s, NH). 13C-NMR (400 MHz,
CDCl3): 12.2 (d, Me2CH); 18.2 (q, Me2CH); 55.6 (q, MeO); 63.9 (t, C(5’)); 71.4 (d, C(2’)); 82.9 (d, C(3’));
84.8 (d, C(4’)); 87.1 (d, C(1’)); 87.4 (s, arom. C); 91.3 (t, OCH2O); 113.6 (d, arom. C); 125.7 (s, C(5)); 127.4,
128.3, 128.6, 129.5, 130.5 (5d, arom. C), 136.0, 136.1 (2s, arom. C); 139.5 (d, C(8)); 144.9 (s, arom. C); 145.2
(s, C(4)); 149.3 (s, C(2)); 158.9 (s, C(6)); 159.6 (s, arom. C). ESI-MS: 757.34 (100, [M+H]+).
5’-O-(4,4’-Dimethoxytrityl)-1-methyl-2’-O-{[(triisopropylsilyl)oxy]methyl}inosine (18). A soln. of 17 (76 mg,
0.1 mmol) in DMF was treated with K2CO3 (15 mg, 0.1 mmol), stirred for 1.5 h at ꢀ158, treated with MeI (31
mg, 0.2 mmol), and stirred for 2 h at r.t. Workup, evaporation, and CC (SiO2 (2 g), hexane/AcOEt 3 :2 !
AcOEt) gave 17 (77 mg, 98%). White solid. TLC (CH2Cl2/MeOH 19 :1): Rf 0.50. 1H-NMR (400 MHz,
i
CDCl3): 1.00–1.12 (m, Pr3Si); 2.99 (d, J=4.7, OHꢀC(3’)); 3.39 (dd, J=4.2, 10.4, HꢀC(5’)); 3.43 (dd, J=3.4,
10.4, H’ꢀC(5’)); 3.61 (s, MeꢀN(1)); 3.78 (s, 2 MeO); 4.29 (q, J=4.1, HꢀC(4’)); 4.53 (q, J=4.2, HꢀC(3’));
4.82 (t, J=5.0, HꢀC(2’)); 4.94, 5.13 (2d, J=4.8, OCH2O); 6.11 (d, J=4.9, HꢀC(1’)); 6.81 (m, 4 arom. H);
7.18–7.35, 7.41–7.47 (m, 9 arom. H); 7.83 (s, HꢀC(8)); 7.93 (s, HꢀC(2)). 13C-NMR (100 MHz, CDCl3): 12.2
(d, Me2CH); 18.1 (q, Me2CH); 34.5 (q, MeN(1)); 55.6 (q, MeO); 64.0 (t, C(5’)); 71.5 (d, C(3’)); 82.8 (d,
C(2’)); 84.8 (d, C(4’)); 86.8 (s, arom. C); 87.0 (d, C(1’)); 91.3 (t, OCH2O); 113.6 (d, arom. C); 125.5 (s, C(5));
127.29, 128.23, 128.56, 130.48, 130.51 (5d, arom. C); 136.0, 136.1 (2s, arom. C); 139.2 (d, C(8)); 145.0 (s, arom.
C); 147.5 (s, C(4)); 148.1 (s, C(2)); 157.4 (s, C(6)); 159.0 (s, arom. C). ESI-MS: 771.40 (100, [M+H]+).
3’,5’-Di-O-acetyl-N6-isopent-2-enyl-2’-O-{[(triisopropylsilyl)oxy]methyl}adenosine (20). A soln. of isopent-
2-enylamine·HCl (264 mg, 2.2 mmol) in pyridine (5 ml) was treated with Et3N (0.6 ml, 4.3 mmol) and 19 (200
mg, 0.3 mmol; prepared according to [24]), and stirred for 1 h at r.t. Workup and CC (SiO2 (5 g), hexane/
AcOEt 9 :1 ! 3 :7) gave 20 (200 mg, 89%). Yellow foam. TLC (hexane/AcOEt 1:1): Rf 0.50. 1H-NMR (100
i
MHz, CDCl3): 0.89–1.05 (m, Pr3Si); 1.76 (s, Me); 1.78 (s, Me); 2.13 (s, MeCO); 2.18 (s, MeCO); 4.23 (br. s,
CH2NH); 4.37–4.50 (m, HꢀC(3’), HꢀC(4’), CH2(5’)); 4.86 (d, J=4.7, 1 H, OCH2O); 4.92 (d, J=4.7, 1 H,
OCH2O); 5.22 (t, J=6.3, CH=C); 5.64 (br. s, HꢀC(2’)); 6.13 (d, J=5.7, HꢀC(1’)); 7.88 (s, HꢀC(8)); 8.47
(br. s, HꢀC(2)). 13C-NMR (100 MHz, CDCl3): 12.1 (q, MeC=); 12.2 (d, Me2CH); 18.0 (q, Me2CH); 18.4 (q,
Me’C=); 21.2 (q, 2 MeCO); 26.1 (t, CH2NH); 63.9 (t, C(5’)); 71.9 (d, C(3’)); 76.7 (d, C(2’)); 80.9 (d, C(4’));
87.8 (d, C(1’)); 89.9 (t, OCH2O); 107.6 (s, CH=C); 120.6 (s, C(5)); 137.4 (s, Me2C=); 138.9 (d, C(8)); 152.9
(s, C(4)); 153.8 (d, C(2)); 155.1 (s, C(6)); 170.5 (s, MeCO); 170.8 (s, MeCO). ESI-MS: 606.80 (100, [M+H]+).
5’-O-(4,4’-Dimethoxytrityl)-N6-isopent-2-enyl-2’-O-{[(triisopropylsilyl)oxy]methyl}adenosine (21). A soln.
of 20 (100 mg, 0.16 mmol), was treated with a sat. NH3 soln. in MeOH (3 ml) for 6 h at r.t. After evaporation,
the residue was dissolved in pyiridine (0.7 ml), treated with (MeO)2TrCl (67 mg, 0.19 mmol), and stirred for 4 h
at r.t. Workup and CC (SiO2 (2 g), hexane/AcOEt 8 :2 ! 3 :7) gave 21 (81 mg, 60%). Yellow foam. TLC (hex-
ane/AcOEt 1 :1): Rf 0.53. 1H-NMR (400 MHz, CDCl3): 0.90–1.06 (m, iPr3Si); 1.73 (s, Me); 1.78 (s, Me); 2.84 (s,
OHꢀC(3’)); 3.39 (dd, J=4.7, 10.2, HꢀC(5’)); 3.47 (dd, J=3.9, 10.2, H’ꢀC(5’)); 3.79 (s, 2 MeO); 4.01 (d, J=4.7,
HꢀC(4’)); 4.22–4.24 (m, CH2NH); 4.69 (d, J=4.7, HꢀC(3’)); 5.10 (s, OCH2O); 5.22 (t, J=4.7, CH=C); 5.42–
5.44 (m, HꢀC(2’)); 6.17 (d, J=4.7, HꢀC(1’)); 6.83–6.87 (m, 4 arom. H); 7.22–7.49 (m, 9 arom. H); 8.13 (s, Hꢀ
C(8)); 8.19 (br. s, HꢀC(2)); 12.98 (br. s, NH). 13C-NMR (100 MHz, CDCl3): 12.1 (d, Me2CH); 17.6 (q, Me2CH);
28.8 (q, MeC=); 29.9 (q, Me’C=); 38.4 (t, CH2NH); 54.9 (q, MeO); 64.0 (t, C(5’)); 70.9 (d, C(3’)); 79.7 (d, C(2’));
84.5 (d, C(4’)); 86.5 (d, C(1’)); 87.5 (s, arom. C); 90.2 (t, OCH2O); 109.4 (s, CH=C); 113.4 (d, arom. C); 122.2 (s,
C(5)); 127.0, 128.0, 128.5, 130.4, 130.5 (5d, arom. C), 134.6, 136.4 (2s, arom. C, Me2C=); 139.8 (d, C(8)); 145.2 (d ,
C(4)); 145.6 (s, arom. C); 153.1 (d, C(2)); 155.3 (s, C(6)); 159.1 (s, arom. C). ESI-MS: 824.37 (100, [M+H]+).
5’-O-(4,4’-Dimethoxytrityl)-N6-methyl-2’-O-{[(triisopropylsilyl)oxy]methyl}adenosine (22). A soln. of 19
(150 mg, 0.2 mmol; prepared according to [24]) was treated with a 33% MeNH2 soln. in EtOH (3 ml) for 3 h