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Helvetica Chimica Acta – Vol. 89 (2006)
(160 ml), PrOH (17.9 g, 297 mmol, 20 equiv.), and Et3N (4.5 g, 44.6 mmol, 3.0 equiv.) was stirred at
60–658 for 72 h. The mixture was evaporated and co-evaporated with toluene (50 ml). The residue
was dissolved in CH2Cl2 (400 ml), the soln. washed with 20% aq. citric acid soln. (2×100 ml) and sat.
aq. NaHCO3 soln. (6×200 ml), dried (Na2SO4), and evaporated after addition of silica gel (35 g). The res-
idue was subjected to CC (silica gel (620 g), 25×8 cm, linear gradient AcOEt/hexanes 1:20 ! 1:1 in 4 l,
then isocratic 1:1): 3.67 g (25%) of starting 7 and 3.78 g (32%) 8. Slightly yellowish foam. TLC (AcOEt/
hexanes 1:1): Rf 0.31. 1H-NMR (300 MHz, CDCl3): 1.97 (s, Me); 2.82 (dd, J=5.1, 11.2, 1HÀC(5’));
3.65–3.9, 3.95–4.05 (2m, HÀC(2’), HÀC(4’), 1 HÀC(5’)); 3.79 (s, MeO); 5.95 (br. s, HÀC(3’)); 6.56
(d, J=9.3, HÀC(1’)); 6.75–6.85, 7.1–7.45, 7.5–7.65, 7.7–7.8 (4m, arom. H); 7.97 (d, J=7.2, arom. H);
8.37 (d, J=7.2, arom. H); 13.48 (br. s, NH). 13C-NMR (50 MHz, CDCl3): 13.06 (q, Me); 55.25 (q,
MeO); 66.36 (t, C(5’)); 67.77, 71.28, 73.95 (3d, C(2’), C(3’), C(4’)); 81.63 (d, C(1’)); 87.45 (s); 113.41
(d); 115.59 (s, C(5)); 127.13, 127.98, 128.93, 129.05, 129.95, 130.11, 132.18, 133.64, 134.24 (9d, arom. C,
therein C(6)); 135.76, 135.92, 136.27, 144.83 (4s, arom. C); 154.68, 158.86, 160.09 (3s, C(2), C(4), arom.
C); 166.15 (s, CO); 176.96 (s, PhCONH). EI-MS: 768 (16, M+), 767 (48, [MÀ1]+), 766 (96), 372 (31),
283 (14), 281 (19), 255 (36), 253 (13), 229 (16), 228 (100), 216 (16), 215 (88), 146 (19), 145 (12), 144
(13), 121 (40), 97 (34), 77 (10), 60 (13).
N2-Benzoyl-1-[3-O-benzoyl-4-O-[bis(4-methoxyphenyl)phenylmethyl]-b-D-ribopyranosyl}-5-methyl-
isocytosine 2’-[Prop-2-enyl Diisopropylphosphoramidite] (diastereoisomer mixture; 9). A soln. of 8 (1.92
i
g, 2.5 mmol, 1.0 equiv.) in abs. CH2Cl2 (10 ml) was stirred at r.t. in the presence of Pr2NEt (1.29 g, 10
mmol, 4.0 equiv.) and prop-2-enyl diisopropylphosphoramidochloridite (0.70 g, 3.75 mmol, 1.5 equiv.)
for 2 h. The mixture was then concentrated to 5 ml and directly subjected to CC (silica gel (80 g);
14×4.5 cm, linear gradient hexanes/AcOEt 10 :1 ! 1:1 in 1 l; all eluents contained 2% of Et3N). Product
fractions were evaporated (<408), then co-evaporated with CCl4 (4 ml): 1.90 g (79%) of 9. Colorless
foam. TLC (AcOEt/hexanes/Et3N 39 :59 :2): Rf 0.45. 1H-NMR (300 MHz, CDCl3): 0.68 (d, J=6.7,
Me2CH); 0.87 (d, J=6.7, Me2CH); 0.96 (t, J=6.4); 1.27 (dd, J=3.0, 6.8); 1.95, 1.98 (2s, Me); 2.41, 2.63
(2 dd, J=5.0, 11.0, HÀC(5’)); 3.2–3.45, 3.45–3.85, 3.85–4.2 (3m); 3.78, 3.79 (2s, MeO); 4.4–4.6,
4.95–5.1, 5.15–5.3, 5.3–5.5, 5.55–5.7, 5.85–6.05 (6m); 6.07, 6.29 (br. s, HÀC(3’)); 6.75–6.9, 7.1–7.55,
7.62–7.72 (3m, arom. H, therein HÀC(1’)); 8.13 (d, J=8.0, arom. H); 8.29 (t, J=7.3, arom. H); 13.46
(br. s, NH). 13C-NMR (50 MHz, CDCl3): 13.01, 13.08, 22.90, 22.95, 24.06, 24.14, 24.24, 24.32, 42.78,
43.02, 45.15, 45.27 (12q, Me); 55.21 (q, MeO); 63.11, 63.44, 63.84, 63.98, 64.15, 66.01 (6t, C(5’)); 68.02,
68.11, 70.35, 70.44, 70.62, 73.00, 73.73 (7d); 80.33, 80.49 (2d, C(1’)); 87.38, 87.44, 87.53 (3s); 113.37,
113.45 (2d); 114.69, 114.99 (2s); 115.41, 116.07, 117.32 (3t); 127.02, 127.90, 128.01, 128.71, 128.94,
129.40, 129.74, 130.17, 130.65, 130.79, 131.79, 131.86, 132.99, 133.05, 134.70, 134.86, 135.00, 135.11,
135.17, 135.90 (20d, arom. C); 136.00, 136.06, 136.22, 137.15, 137.24, 145.01, 145.05 (7s, arom. C);
154.14, 154.22, 160.41, 160.54 (4s, C(2), C(4)); 158.81, 158.84 (2s); 165.59 (s, CO); 177.46, 177.56 (s,
PhCONH). FAB-MS: 955 (10, M+), 856 (20), 855 (57), 854 (100), 850 (22), 849 (42), 750 (14), 304
(33), 303 (90), 188 (25), 146 (11), 105 (10), 104 (50), 102 (16).
N2-Benzoyl-1-{3-O-benzoyl-4-O-[bis(4-methoxyphenyl)phenylmethyl]-b-D-ribopyranosyl}-5-methyl-
isocytosine 2’-[(4-Nitrophenyl) Heptanedioate] (10). A soln. of DMAP (52 mg, 0.422 mmol, 1.0 equiv.),
bis(4-nitrophenyl) heptanedioate (1.24 g, 3.08 mmol, 7.3 equiv.), and 9 (324 mg, 0.422 mmol, 1.0 equiv.)
in pyridine (3 ml) was stirred for 17 h. The mixture was evaporated, treated with toluene (6 ml), and
evaporated. The residue was subjected to CC (silica gel (30 g), 12×2.5 cm, linear gradient AcOEt/hex-
1
anes 1:6 ! 1:1 in 0.8 l): 264 mg (61%) of 10. Colorless foam. TLC (AcOEt/hexanes 1:1): Rf 0.49. H-
NMR (300 MHz, CDCl3): 1.05–1.2, 1.3–1.55 (2m); 1.97 (s, Me); 1.95–2.2 (m); 2.41 (t, J=7.4); 2.85
(dd, J=5.0, 11.1, HÀC(5’)); 3.79 (s, MeO); 3.87 (t, J=11.0); 3.95–4.1 (m); 4.95 (dd, J=2.5, 9.5, HÀ
C(2’)); 5.89 (br. s, HÀC(3’)); 6.75–6.85, 6.85–7.05, 7.2–7.3, 7.3–7.45 (4m, arom. H, therein HÀC(1’));
7.59 (t, J=7.7, arom. H); 7.76 (t, J=7.4, arom. H); 8.07 (d, J=7.2, arom. H); 8.15 (d, J=9.1, arom.
H); 8.23 (d, J=9.1, arom. H); 8.33 (d, J=7.2, arom. H); 13.37 (br. s, NH). 13C-NMR (50 MHz,
CDCl3): 13.04 (q, Me); 24.00, 24.02, 28.12, 33.58, 33.79 (5t); 55.26 (q, MeO); 66.31 (t, C(5’)); 67.31,
67.54, 68.70 (3d, C(2’), C(3’), C(4’)); 79.13 (d, C(1’)); 87.48 (s); 113.47 (d); 113.54 (d); 115.28 (s, C(5));
115.63 (d); 122.44, 125.12, 126.17, 127.23, 127.96, 128.07, 128.98, 129.31, 129.90, 130.06, 132.14, 133.64,
134.60 (13d, arom. C, therein C(6)); 135.57, 135.74, 136.75, 144.71, 145.23 (5s, arom. C); 153.58, 160.30