2562
Helvetica Chimica Acta Vol. 86 (2003)
(m, 2 HÀC(5'), CH2OCH2); 3.15 (t, CH2CH2O); 3.08 2.78 (m, CH2 (2c1peoc), MeO); 1.82 1.54
(m, CH2CCH2). Anal. calc. for C33H36N4O12 (680.7): C 58.23, H 5.33, N 8.23; found: C 58.95, H 5.58, N 7.71.
Data of 44: Colorless foam. TLC (toluene/AcOEt/MeOH 5 :4 :1): Rf 0.61. UV (MeOH): 274 (4.24), 211
(sh, 4.56). 1H-NMR (CDCl3): 8.16 (d, 2 Ho to NO2); 7.65, 7.59, 7.58 (3 d, HÀC(6)); 7.38 (m, 2 Hm to NO2, 2 Ph
(2c1peoc)); 6.20, 6.17 (2 d, HÀC(1')); 5.99, 5.76, 5.74 (3 d, HÀC(5)); 5.80( m, 2 CH (2c1peoc)); 4.98
(m, HÀC(3')); 4.71 4.59 (m, HÀC(2')); 4.35 (m, CH2CH2O, HÀC(4'), 2 HÀC(5')); 3.72 3.35
(m, CH2OCH2); 3.14 (t, CH2CH2O); 3.08, 3.05, 2.85, 2.83 (4 s, MeO); 2.93 (m, 2 CH2 (2c1peoc)); 1.83 1.65
(m, CH2CCH2). Anal. calc. for C43H43N5O14 (853.8): C 60.49, H 5.08, N 8.20; found: C 60.02, H 5.29, N 8.17.
15. 5'-O-[(2-Cyano-1-phenylethoxy)carbonyl]-N6-{[2-(4-nitrophenyl)ethoxy]carbonyl}-2'-O-(tetrahydro-4-
methoxy-2H-pyran-4-yl)adenosine 3'-[2-(4-Nitrophenyl)ethyl Diisopropylphosphoramidite] (46). A soln. of 33
(0.19 g, 0.25 mmol), 2-(4-nitrophenyl)ethyl tetraisopropylphosphordiamidite [24] (45; 0.2 g, 0.51 mmol), and
1H-tetrazole (9 mg, 0.13 mmol) in dry CH2Cl2 (1.6 ml) was stirred overnight under N2 for 15 h. After dilution
with CH2Cl2 (20ml), the soln. was washed with 5% NaHCO 3/sat. NaCl soln. 2 :1 (30ml), the aq. layer extracted
with CH2Cl2 (2 Â 30ml), the combined org. phase dried (Na 2SO4) and evaporated, and the residue purified by
FC (silica gel (10g), 14.5 Â 1.7 cm, petroleum ether/acetone 3 :1 (80 ml), 3 :2 (100 ml), 1 :1 (100 ml), 2 :3
(100 ml)): 215 mg (81%) of 46. Colorless foam. TLC (petroleum ether/acetone 3 :2): Rf 0.22. UV (MeOH): 275
(sh, 4.50), 267 (4.55), 211 (sh, 4.71). 1H-NMR (CDCl3): 8.73, 8.72, 8.70(3 s, HÀC(2)); 8.19 8.10( m, 4 Ho to
NO2, NH, HÀC(8)); 7.45 7.31 (m, 4 Hm to NO2, Ph (2c1peoc)); 6.13, 6.05 (2 d, HÀC(1')); 5.84 (m, CH
(2c1peoc)); 5.28, 5.17 5.10(2 m, HÀC(2')); 4.52 (t, CH2CH2O (N6-npeoc)); 4.43 3.84 (m, CH2OP, HÀC(3'),
HÀC(4'), 2 HÀC(5')); 3.78 3.25 (m, CH2OCH2, 2 Me2CH); 3.15 (t, CH2CH2O (N6-npeoc)); 3.05 2.91
(m, CÀCH2, CH2 (2c1peoc)); 2.65, 2.62, 2.58 (3 s, MeO); 1.86 1.39 (m, CH2CCH2); 1.26 1.05 (m, 2 Me2CH).
31P-NMR (CDCl3): 151.14; 151.20; 149.42; 149.13. Anal. calc. for C49H58N9O15P (1044.0): C 56.37, H 5.60, N
12.07; found: C 56.08, H 5.87, N 11.59.
16. 5'-O-[(2-Cyano-1-phenylethoxy)carbonyl]-N4-{[2-(4-nitrophenyl)ethoxy]carbonyl}-2'-O-(tetrahydro-4-
methoxy-2H-pyran-4-yl)cytidine 3'-[2-(4-Nitrophenyl)ethyl Diisopropylphosphoramidite] (47). As described in
Exper. 15, with 35 (962 mg, 1.33 mmol), 45 (1.06 g, 2.66 mmol), 1H-tetrazole (47 mg, 0.67 mmol), and dry
CH2Cl2 (12 ml); stirring for 17 h. Workup with CH2Cl2 (80ml), 5% NaHCO 3/sat. NaCl 4 :1 soln. (100 ml), and
CH2Cl2 (2 Â 100 ml). FC (silica gel (50 g), 19 Â 3 cm, petroleum ether/acetone 3 :1 (200 ml), 2 :1 (225 ml), 3 :2
(250 ml), 1:1 (300 ml)) gave 1.03 g (76%) of 47. Colorless foam. TLC (petroleum ether/acetone 3 :2): Rf 0.23.
UV (MeOH): 269 (4.50), 252 (sh, 4.48), 212 (sh, 4.70). 1H-NMR (CDCl3): 8.14 (m, 4 Ho to NO2); 7.82
(m, HÀC(6)); 7.54 (br. s, NH); 7.38 (m, 4 Hm to NO2, Ph (2c1peoc)); 7.29 7.09 (m, HÀC(5)); 6.21, 6.09, 6.07
(3 d, HÀC(1')); 5.85 (m, CH (2c1peoc)); 4.44 4.31 (m, HÀC(2'), 2 CH2O); 4.11 3.46 (m, HÀC(3'),
HÀC(4'), 2 HÀC(5'), CH2OCH2, 2 Me2CHN); 3.13 2.86 (m, 2 CH2CH2O, CH2 (2c1peoc), MeO); 1.83 1.47
(m, CH2CCH2); 1.18 1.00 (m, 2 Me2CH). 31P-NMR (CDCl3): 150.67; 150.61; 149.41; 148.88. Anal. calc. for
C48H58N7O16P (1020.0): C 56.52, H 5.73, N 9.61; found: C 56.36, H 5.92, N 9.47.
17. 5'-O-[(2-Cyano-1-phenylethoxy)carbonyl]-N2-{[2-(4-nitrophenyl)ethoxy]carbonyl}-O6-[2-(4-nitrophen-
yl)ethyl]-2'-O-(tetrahydro-4-methoxy-2H-pyran-4-yl)guanosine 3'-[2-(4-Nitrophenyl)ethyl Diisopropylphos-
phoramidite] (48). As described in Exper. 15, with 38 (976 mg, 1.07 mmol), 45 (850mg, 2.14 mmol), 1 H-
tetrazole (37 mg, 0.53 mmol), and CH2Cl2 (10ml), stirring for 19 h. Workup with CH 2Cl2 (80ml), 5% NaHCO 3/
sat. NaCl 4 :1 soln. (100 ml), and CH2Cl2 (2 Â 100 ml). FC (silica gel (50 g), 19 Â 3 cm, petroleum ether/acetone
3 :1 (200ml), 2 :1 (225 ml), 3 :2 (250ml), 1 :1 (250ml)) gave 880mg (68%) of
48. Colorless foam. TLC
(petroleum ether/acetone 3 :2): Rf 0.24. UV (MeOH): 279 (sh, 4.54), 269 (4.61), 212 (sh, 4.73). 1H-NMR
(CDCl3): 8.21 8.10( m, 6 Ho to NO2); 7.91, 7.89, 7.86 (3 s, HÀC(8)); 7.51 7.22 (m, 6 Hm to NO2, Ph (2c1peoc),
NH); 6.00 5.83 (4 d, HÀC(1')); 5.76 (m, CH (2c1peoc)); 5.40, 5.28 (2 m, HÀC(2')); 4.83 4.75 (m, CH2CH2O
(O6-npe)); 4.68 3.40( m, 2 CH2O, HÀC(3'), HÀC(4'), 2 HÀC(5'), CH2OCH2, 2 Me2CH); 3.29 (t, CH2CH2O
(O6-npe)); 3.12 2.96 (m, 2 CÀCH2); 2.87 (m, CH2 (2c1peoc)); 2.56, 2.55, 2.54, 2.52 (4 s, MeO); 1.75 1.48
(m, CH2CCH2); 1.23 1.07 (m, 2 Me2CH). 31P-NMR (CDCl3): 151.37, 151.31, 149.47, 149.44. Anal. calc. for
C57H65N10O18P (1209.2): C 56.62, H 5.42, N 11.58; found: C 56.64, H 5.59, N 11.18.
18. 5'-O-[(2-Cyano-1-phenylethoxy)carbonyl]-2'-O-(tetrahydro-4-methoxy-2H-pyran-4-yl)uridine 3'-[2-(4-
Nitrophenyl)ethyl Diisopropylphosphoramidite] (49). As described in Exper. 15, with 40 (1.60g, 3.01 mmol), 45
(2.40g, 6.03 mmol), 1 H-tetrazole (106 mg, 1.51 mmol), and CH2Cl2 (25 ml), stirring for 17 h. Workup with
CH2Cl2 (80ml), 5% NaHCO 3/sat. NaCl 4 :1 soln. (100 ml), and CH2Cl2 (2 Â 100 ml). FC (silica gel (40 g), 15 Â
3 cm, petroleum ether/acetone 3 :1 (200ml), 2 :1 (225 ml), 3 :2 (250ml), 1:1 (300ml)) gave 1.86 g (75%) of
49.
Colorless foam. TLC (petroleum ether/acetone 3 :2): Rf 0.22. UV (MeOH): 263 (4.25), 213 (sh, 4.41). 1H-NMR
(CDCl3): 8.14 (m, 2 Ho to NO2, NH); 7.42 7.29 (m, 2 Hm to NO2, Ph (2c1peoc), HÀC(6)); 6.12, 6.02
(2 d, HÀC(1')); 5.83 (m, CH (2c1peoc)); 5.52, 5.51 (2 d, HÀC(5)); 4.45 (m, CH2CH2O, HÀC(2'), HÀC(3'),