1374 J . Org. Chem., Vol. 62, No. 5, 1997
Ichikawa et al.
(d, J ) 7.6 Hz, 1H), 4.80 (d, J ) 7.6 Hz, 1H), 4.40 (br s, 1H),
4.00-3.98 (m, 4H), 3.73 (s, 3H), 3.15 (br s, 1H), 3.10 (d, J )
16.1 Hz, 1H), 2.66 (d, J ) 16.1 Hz, 1H), 1.21 (t, J ) 7.1 Hz,
3H), 0.88 (s, 9H), 0.08 (s, 3H), -0.13 (s, 3H); 13C NMR (CDCl3,
125 MHz) δ 172.4, 163.6, 152.7, 143.5, 104.3, 96.1, 88.2, 63.8,
53.4, 40.54, 37.9, 27.1, 19.2, 14.2, -3.41; MS (EI) m/ z 458 (M+).
Anal. Calcd for C20H34N2O8Si: C, 52.38; H, 7.47; N, 6.11.
Found: C, 52.70; H, 7.74; N, 5.81.
4-Eth oxy-1-[2-O-(ter t-bu tyld im eth ylsilyl)-3-C-(ca r ba m -
oylm et h yl)-â-D-r ibo-p en t ofu r a n osyl]-2(1H )-p yr im id on e
(17). To a solution of 14 (214 mg, 0.500 mmol) in MeOH (1
mL) was added saturated methanolic ammonia (5 mL) at -70
°C. The mixture was stirred at the same temperature for 3 h
and then evaporated under reduced pressure. The residue was
purified by column chromatography (SiO2, 10% MeOH-CHCl3)
to give 17 (217 mg, 98%) as a colorless glass: mp 170-172 °C
(MeOH-CHCl3); 1H NMR (CDCl3, 500 MHz) δ 7.51 (d, J )
8.0 Hz, 1H), 6.68 (br s, 1H), 5.81 (d, J ) 8.0 Hz, 1H), 5.66 (d,
J ) 7.6 Hz, 1H), 5.50 (br s, 1H), 4.58 (d, J ) 7.4 Hz, 1H), 4.28
(br s, 1H), 4.00 (q, J ) 7.1 Hz, 2H), 3.90 (dd, J ) 2.2 Hz, 12.7
Hz, 1H), 3.79 (d, J ) 12.7 Hz, 1H), 3.64 (br s, 1H), 2.86 (d, J
) 15.9 Hz, 1H), 2.61 (d, J ) 15.9 Hz, 1H), 1.21 (t, J ) 7.1 Hz,
3H), 0.88 (s, 9H), 0.07 (s, 3H), -0.11 (s, 3H); 13C NMR (CDCl3,
125 MHz) δ 172.6, 161.7, 151.1, 140.1, 138.8, 102.1, 86.8, 86.1,
78.0, 77.7, 60.9, 38.3, 35.6, 25.7, 17.8, 12.8, -4.2, -5.0; MS
(FAB) m/ z 443 (M+). Anal. Calcd for C19H33N3O7Si: C, 51.45;
H, 7.50; N, 9.47. Found: C, 51.45; H, 7.77; N, 9.79.
whole was stirred for additional 15 min. Compound 21 (4.72
g, 8.00 mmol) in CH2Cl2 (50 mL) was added to the resulting
mixture, which was stirred at room temperature for 30 min.
The solution was diluted with Et2O (1.5 L) and filtered through
a Celite pad, and the filtrate was evaporated under reduced
pressure. The residue was partitioned between EtOAc (500
mL) and H2O (300 mL). The organic layer was washed with
water (200 mL × 2) and brine (100 mL), dried (Na2SO4), and
evaporated under reduced pressure. The residue was purified
by column chromatography (SiO2, 25% EtOAc-hexane) to give
23 (3.77 g, 80%) as a colorless glass: 1H NMR (CDCl3, 500
MHz) δ 7.75 (d, J ) 8.2 Hz, 1H), 7.31-7.18 (m, 5H), 6.24 (d,
J ) 8.0 Hz, 1H), 5.79 (d, J ) 8.2 Hz, 1H), 5.44 (d, J ) 13.4 Hz,
1H), 5.41 (d, J ) 13.4 Hz, 1H), 4.62 (s, 2H), 4.17 (s, 1H), 4.10
(d, J ) 8.0 Hz, 1H), 3.87 (dd, J ) 1.9, 11.3 Hz, 1H), 3.83 (dd,
J ) 1.6, 11.3 Hz, 1H), 0.83 (s, 9H), 0.77 (s, 9H), 0.05 (s, 3H),
0.04 (s, 3H), 0.03 (s, 3H), 0.01 (s, 3H); 13C NMR (CDCl3, 125
MHz) δ 208.6, 162.5, 151.4, 138.0, 128.5, 127.9, 103.5, 85.9,
82.2, 72.3, 70.6, 63.1, 26.0, 25.6, 18.5, 18.4, 11.7, -4.6, -5.2,
-5.4, -5.5; MS (FAB) m/ z 591 (MH+). Anal. Calcd for
C29H46N2O7Si2: C, 58.95; H, 7.85; N, 4.74. Found: C, 58.68;
H, 7.71; N, 4.39.
3-[(Ben zyloxy)m eth yl]-1-[2-O-(ter t-bu tyld im eth ylsilyl)-
â-D-er yth r o-p en tofr a n -3-u losyl]u r a cil (25). A solution of
23 (590 mg, 1.00 mmol) in 90% aqueous TFA (10 mL) was
stirred at 0 °C for 30 min. The mixture was evaporated under
reduced pressure. The residue was purified by column chro-
matography (SiO2, CHCl3) to give 25 (323 mg, 68%) as a yellow
glass: 1H NMR (CDCl3, 500 MHz) δ 7.41 (d, J ) 8.1 Hz, 1H),
7.27-7.16 (m, 5H), 5.77 (d, J ) 8.1 Hz, 1H), 5.70 (d, J ) 7.6
Hz, 1H), 5.40 (d, J ) 13.5 Hz, 1H), 5.37 (d, J ) 13.5 Hz, 1H),
4.58 (s, 2H), 4.57 (d, J ) 7.6 Hz, 1H), 4.16 (br s, 1H), 3.85 (dd,
J ) 2.3, 12.1 Hz, 1H), 3.80 (dd, J ) 2.2, 12.1 Hz, 1H), 0.75 (s,
9H), 0.01 (s, 3H), -0.09 (s, 3H); 13C NMR (CDCl3, 125 MHz) δ
208.6, 162.4, 151.5, 140.6, 137.8, 128.6, 128.1, 127.9, 103.5,
91.0, 82.5, 75.1, 72.5, 70.6, 62.0, 25.9, 25.7, 18.3, -4.41, -5.3;
MS (EI) m/ z 476 (M+).
3-[(Ben zyloxy)m eth yl]-1-[5-O-(br om oa cetyl)-2-O-(ter t-
b u t yld im e t h ylsilyl)-â-D -er yt h r o-p e n t ofr a n -3-u losyl]-
u r a cil (27). Compound 27 was prepared from 25 (323 mg,
0.68 mmol) as described above for the synthesis of 12. After
purification by column chromatography (SiO2, 30% EtOAc-
hexane), 27 was obtained as a yellow foam (348 mg, 86%): 1H
NMR (CDCl3, 500 MHz) δ 7.44 (d, J ) 8.1 Hz, 1H), 7.36-7.20
(m, 5H), 5.96 (d, J ) 6.8 Hz, 1H), 5.88 (d, J ) 8.1 Hz, 1H),
5.48 (d, J ) 11.7 Hz, 1H), 5.47 (d, J ) 11.7 Hz, 1H), 4.68 (s,
2H), 4.56 (dd, J ) 1.0, 11.3 Hz, 1H), 4.49 (d, J ) 6.8 Hz, 1H),
4.46 (br s, 1H), 4.45 (dd, J ) 3.8, 11.3 Hz, 1H), 3.90 (s, 2H),
0.85 (s, 9H), 0.11 (s, 3H), 0.04 (s, 3H); 13C NMR (CDCl3, 125
MHz) δ 206.1, 166.3, 162.2, 151.4, 139.0, 137.9, 128.6, 128.0,
127.9, 103.6, 89.1, 75.3, 72.4, 70.65, 64.6, 26.0, 25.6, 25.5, 18.3,
-4.4, -5.0; MS (FAB) m/ z 597, 599 (MH+).
3-[(Ben zyloxy)m eth yl]-1-[2-O-(ter t-bu tyld im eth ylsilyl)-
3-C-(ca r boxym eth yl)-â-D-r ibo-p en tofu r a n osyl]u r a cil 3′,5′-
La cton e (29). Compound 29 was prepared from 27 (338 mg,
0.57 mmol) as described above for the synthesis of 14. After
purification by column chromatography (SiO2, 30% EtOAc-
hexane), 29 was obtained as a yellow glass (236 mg, 80%): mp
114-117 °C (MeOH-CHCl3); 1H NMR (CDCl3, 500 MHz) δ
7.36-7.25 (m, 5H), 7.13 (d, J ) 8.1 Hz, 1H), 6.06 (d, J ) 7.5
Hz, 1H), 5.99 (d, J ) 8.1 Hz, 1H), 5.48 (d, J ) 11.7 Hz, 1H),
5.47 (d, J ) 11.7 Hz, 1H), 4.67 (s, 2H), 4.46 (d, J ) 13.1, 1H),
4.42 (br s, 1H), 4.38 (dd, J ) 1.4, 13.1 Hz, 1H), 3.64 (d, J ) 7.5
Hz, 1H), 3.52 (s, 1H), 2.78 (d, J ) 15.3 Hz, 1H), 2.71 (d, J )
15.3 Hz, 1H), 0.87 (s, 9H), 0.09 (s, 3H), -0.08 (s, 3H); 13C NMR
(CDCl3, 125 MHz) δ 151.4, 137.3, 128.6, 128.0, 127.9, 104.3,
85.5, 81.3, 74.1, 72.3, 70.6, 68.4, 40.6, 25.7, 17.9, -4.55, -4.68;
MS (FAB) m/ z 519 (MH+). Anal. Calcd for C25H34N2O8Si: C,
57.90; H, 6.61; N, 5.40. Found: C, 57.64; H, 6.64; N, 5.76.
1-[5-O-(Br om oa cetyl)-2-O-(ter t-bu tyld im eth ylsilyl)-â-D-
er yth r o-p en tofr a n -3-u losyl]u r a cil (26). Compound 26 was
prepared from 2418 (4.48 g, 12.6 mmol) as described above for
the synthesis of 12. After purification by column chromatog-
raphy (SiO2, 30% EtOAc-hexane), 26 (4.21 g, 70%) was
obtained as a yellow foam: 1H NMR (CDCl3, 500 MHz) δ 9.69
(br s, 1H), 7.49 (d, J ) 8.2 Hz, 1H), 5.97 (d, J ) 7.1 Hz, 1H),
3-[(Ben zyloxy)m eth yl]-1-(â-D-r ibofu r a n osyl)u r a cil (19).
A mixture of uridine (24.4 g, 100 mmol), DBU (30 mL, 200
mmol), and benzyl chloromethyl ether (20.8 mL, 150 mmol)
in DMF (300 mL) was stirred at 0 °C for 30 min. After MeOH
(10 mL) was added, the solution was evaporated under reduced
pressure. The residue was purified by column chromatography
(SiO2, 10% EtOH-CHCl3) to give 19 (33.9 g, 93%) as a white
1
crystal: mp 265-268 °C (MeOH-CHCl3); H NMR (DMSO-
d6, 500 MHz) δ 7.98 (d, J ) 8.2 Hz, 1H), 7.35-7.26 (m, 5H),
5.81 (d, J ) 4.8 Hz, 1H), 5.78 (d, J ) 8.2 Hz, 1H), 5.41 (d, J )
5.6 Hz, 1H), 5.33 (d, J ) 12.5 Hz, 1H), 5.30 (d, J ) 12.5 Hz,
1H), 5.12 (t, J ) 5.0 Hz, 1H), 5.09 (d, J ) 5.4 Hz, 1H), 4.59 (s,
2H), 4.03 (ddd, J ) 5.6, 4.8 Hz, 1H), 3.97 (ddd, J ) 5.4, 5.0
Hz, 1H), 3.87 (m, 1H), 3.75 (ddd, J ) 3.2, 5.0, 12.2 Hz, 1H),
3.65 (ddd, J ) 3.2, 5.0, 12.2 Hz, 1H); 13C NMR (DMSO-d6, 125
MHz) δ 172.4, 163.6, 152.7, 143.5, 104.3, 96.1, 88.2, 63.8, 53.4,
40.5, 37.9, 27.1, 19.2, 14.2, -3.41; MS (EI) m/ z 364 (M+). Anal.
Calcd for C17H20N2O7: C, 56.04; H, 5.53; N, 7.69. Found: C,
56.01; H, 5.55; N, 7.50.
3-[(Ben zyloxy)m eth yl]-1-[2,5-O-bis(ter t-bu tyld im eth yl-
silyl)-â-D-r ibofu r a n osyl]u r a cil (21). A mixture of 19 (3.64
g, 10.0 mmol), AgNO3 (3.74 g, 22.0 mmol), pyridine (4.04 mL,
50.0 mmol), and tert-butyldimethylsilyl chloride (3.32 g, 22.0
mmol) in THF (100 mL) was stirred at room temperature for
24 h. After MeOH (5 mL) was added, the precipitate was
filtered off. The filtrate was evaporated under reduced pres-
sure, and the residue was partitioned between EtOAc (1 L)
and H2O (300 mL). The organic layer was washed with water
(200 mL × 3) and brine (200 mL), dried (Na2SO4), and
evaporated under reduced pressure. The residue was purified
by column chromatography (SiO2, 30% EtOAc-hexane) to give
21 (5.28 g, 89%) as a white foam: 1H NMR (CDCl3, 500 MHz)
δ 7.87 (d, J ) 8.2 Hz, 1H), 7.27-7.16 (m, 5H), 5.86 (d, J ) 3.7
Hz, 1H), 5.61 (d, J ) 8.2 Hz, 1H), 5.39 (s, 2H), 4.60 (s, 2H),
4.06 (t, J ) 4.0 Hz, 1H), 4.03-4.3.98 (m, 2H), 3.91 (dd, J )
1.3, 11.7 Hz, 1H), 3.73 (dd, J ) 1.2, 11.7 Hz, 1H), 2.48 (br s,
1H), 0.85 (s, 9H), 0.81 (s, 9H), 0.05 (s, 3H), 0.04 (s, 3H), 0.03
(s, 3H), 0.01 (s, 3H); 13C NMR (CDCl3, 125 MHz) δ 162.9, 151.2,
138.9, 138.2, 128.6, 128.5, 128.3, 127.8, 102.0, 89.8, 89.5, 84.9,
72.3, 70.4, 70.3, 62.6, 26.1, 25.9, 18.6, 18.2, 11.7, -4.4, -5.0,
-5.3, -5.4; MS (FAB) m/ z 593 (MH+). Anal. Calcd for
C29H48N2O7Si2: C, 58.75; H, 8.16; N, 4.72. Found: C, 58.56;
H, 8.30; N, 4.52.
3-[(Ben zyloxy)m eth yl]-1-[2,5-O-bis(ter t-bu tyld im eth yl-
silyl)-â-D-er yth r o-pen tofr an -3-u losyl]u r acil (23). To a mix-
ture of molecular sieves 4A (8.00 g) and CrO3 (3.20 g, 32.0
mmol) in CH2Cl2 (100 mL) was added pyridine (5.16 mL, 64.0
mmol) at 0 °C. The mixture was stirred for 30 min, Ac2O (3.04
mL, 32.0 mmol) was added at the same temperature, and the