K. Lee et al. / Tetrahedron: Asymmetry 13 (2002) 1589–1598
1597
7.25 (2s, D2O exchangeable, 2H), 7.53 (d, J=7.2 Hz,
1H, H-6). Anal. calcd for C9H10FN3O3·
0.6H2O·0.1C3H6O: C, 45.81; H, 4.88; N, 17.23. Found:
1H), 7.24 (s, 1H), 8.21 (s, 1H). Anal. calcd for
C10H11FN2O4·0.1C4H10O: C, 50.04; H, 4.85; N, 11.22.
Found: C, 50.12; H, 4.85; N, 11.37%.
C, 46.20; H, 4.69; N, 17.17%.
20b: mp 184–185°C; UV (MeOH) umax 262.0 nm; [h]D25
+16.88 (c 0.23, MeOH); 1H NMR (DMSO-d6) l 1.79 (s,
3H), 3.85 (m, 2H), 4.04 (m, 1H), 5.55 (m, 1H), 5.79 (d,
J=7.8 Hz, 1H), 6.31 (d, J=7.2 Hz, 1H), 7.42 (s, 1H),
11.41 (s, 1H). Anal. calcd for C10H11FN2O4·0.1CH4O:
C, 48.98; H, 4.98; N, 10.98. Found: C, 48.95; H, 4.81;
N, 10.74%.
3.21. (+)-1-[(1R,4S)-3-Fluoro-4-hydroxy-5-dihydro-2,3-
enpyranosyl]cytosine, 16b
Compound 16b was prepared from 15b on a 0.15 mmol
scale by the method described for compound 14a. Silica
gel column chromatography (12.5% MeOH/CH2Cl2)
and subsequent recrystallization from hexanes–MeOH–
CH2Cl2 gave 16b (33.2 mg, 97.4%) as a crystalline solid:
mp 168–170°C; UV (H2O) umax 266.0 nm; [h]2D5 +10.6 (c
3.24. (−)-1-[(1R,4R)-3-Fluoro-4-hydroxy-5-dihydro-2,3-
enpyranosyl]cytosine, 25a
1
0.68, MeOH); H NMR (DMSO-d6) l 3.83 (m, 2H),
4.12 (m, 1H), 5.48 (m, 1H), 5.77 (m, D2O exchangeable,
2H), 6.38 (m, 1H), 7.26, 7.31 (2s, D2O exchangeable,
2H), 7.54 (d, J=7.2 Hz, 1H). Anal. calcd for
C9H10FN3O3·0.6H2O·0.1C3H6O: C, 45.81; H, 4.88; N,
17.23. Found: C, 45.77; H, 4.62; N, 17.23%.
Compound 25a was prepared from 24a on a 0.22 mmol
scale by the method described for compound 16a. Silica
gel column chromatography (12.5% MeOH/CH2Cl2)
gave 25a (45 mg, 88.4%) as a white solid: mp 176–
178°C; UV (H2O) umax 266.0 nm; [h]2D6 −22.4 (c 0.25,
MeOH); 1H NMR (DMSO-d6) l 3.57–3.93 (m, 2H),
4.11 (m, 1H), 5.50 (dd, J=2.8, 14.8 Hz, 1H), 5.66 (d,
J=7.3 Hz, 1H), 5.77 (d, J=6.4 Hz, D2O exchangeable,
1H), 6.44 (m, 1H), 7.21, 7.25 (2s, D2O exchangeable,
2H), 7.53 (d, J=7.2 Hz, 1H). Anal. calcd for
C9H10FN3O3: C, 47.58; H, 4.44; N, 18.50. Found: C,
47.50; H, 4.38; N, 18.25%.
3.22. (+)-1-[(1S,4S)-3-Fluoro-4-hydroxy-5-dihydro-2,3-
enpyranosyl]uracil, 19a and its (+)-(1R,4S)-isomer, 19b
A anomeric mixture 17 (155 mg, 0.47 mmol) was
treated with saturated methanolic ammonia (50 mL)
and the resulting solution was stirred at rt for 10 h. The
reaction mixture was concentrated under reduced pres-
sure and the residue was purified by preparative TLC
(5% MeOH/CH2Cl2) to separate 19a (59.2 mg, 55.2%)
and 19b (43 mg, 40.1%), which were recrystallized from
MeOH–CH2Cl2, respectively.
3.25. (−)-1-[(1S,4R)-3-Fluoro-4-hydroxy-5-dihydro-2,3-
enpyranosyl]cytosine, 25b
Compound 25b was prepared from 24b on a 0.18 mmol
scale by the method described for compound 16a. Silica
gel column chromatography (12.5% MeOH/CH2Cl2)
gave 25b (37.8 mg, 92.5%) as a white solid: mp 167–
169°C; UV (H2O) umax 266.0 nm; [h]2D5 −11.25 (c 0.27,
19a: mp 185–188°C; UV (MeOH) umax 257.0 nm; [h]D24
1
+17.9 (c 0.41, MeOH); H NMR (DMSO-d6) l 3.79–
3.92 (m, 2H), 4.09 (m, 1H), 5.58 (dd, J=1.67, 11.3 Hz,
1H), 5.71 (d, J=8 Hz, D2O exchangeable, 1H), 5.82 (d,
J=7.4 Hz, 1H), 6.35 (m, 1H), 7.64 (d, J=8.0 Hz, 1H),
11.43 (s, 1H). Anal. calcd for C9H9FN2O4: C, 47.37; H,
3.98; N, 12.28. Found: C, 47.36; H, 4.07; N, 12.27.
1
MeOH); H NMR (DMSO-d6) l 3.83 (m, 2H), 4.12 (m,
1H), 5.48 (m, 1H), 5.77 (m, 2H, D2O exchangeable,
1H), 6.38 (m, 1H), 7.26, 7.31 (2s, D2O exchangeable,
2H), 7.54 (d, J=7.2 Hz, 1H). Anal. calcd for
C9H10FN3O3·0.4CH2Cl2: C,43.23; H, 4.17; N, 16.09.
Found: C, 43.33; H, 4.30; N, 16.31%.
19b: mp 182–184°C; UV (MeOH) umax 257.0 nm; [h]D25
1
+34.8 (c 0.26, MeOH); H NMR (DMSO-d6) l 3.63–
3.92 (m, 2H), 4.16 (m, 1H), 5.52 (d, J=2.8 Hz), 5.56
(m, 1H), 5.81 (d, J=6.6 Hz, 1H), 6.32 (d, J=7.2 Hz,
1H), 7.60 (d, J=8.0 Hz, 1H), 11.44 (s, 1H). Anal. calcd
for C9H9FN2O4: C, 47.37; H, 3.98; N, 12.28. Found: C,
47.43; H, 4.11; N, 12.23%.
3.26. (−)-1-[(1R,4R)-3-Fluoro-4-hydroxy-5-dihydro-2,3-
enpyranosyl]uracil, 28a and its (−)-(1S,4R)-isomer, 28b
Compounds 28a and 28b were prepared from 24 on a
0.39 mmol scale by the method described for com-
pounds 19a and 19b. Preparative TLC (5% MeOH/
3.23. (+)-1-[(1S,4S)-3-Fluoro-4-hydroxy-5-dihydro-2,3-
enpyranosyl]thymine, 20a and its (+)-(1R,4S)-isomer,
20b
CH2Cl2)
followed
by
crystallization
from
MeOH–CH2Cl2 gave 28a (48.4 mg, 54.7%) and 28b
(36.5 mg, 41%) as white solids.
Compounds 20a and 20b were prepared from 16 on a
0.42 mmol scale by the method described for com-
pounds 19a and 19b. Preparative TLC (5% MeOH/
CH2Cl2) followed by trituations with ether gave 20a
(54.4 mg, 53.5%) and 20b (39.4 mg, 38.7%) as white
solids.
28a: mp 186–188°C; UV (MeOH) umax 257.0 nm; [h]D25
1
−17.76 (c 0.32, MeOH); H NMR (DMSO-d6) l 3.79–
3.92 (m, 2H), 4.08 (m, 1H), 5.58 (dd, J=1.6, 12 Hz,
1H), 5.71 (d, J=8 Hz, 1H), 5.82 (d, J=7.8 Hz, 1H),
6.35 (m, 1H), 7.64 (d, J=7.8 Hz, 1H), 11.43 (s, 1H).
Anal. calcd for C9H9FN2O4: C, 47.37; H, 3.98; N,
12.28. Found: C, 47.59; H, 4.09; N, 12.37%.
20a: mp 175–176°C; UV (MeOH) umax 263.0 nm; [h]D25
+37.05 (c 0.21, MeOH); 1H NMR (DMSO-d6) l 1.87 (s,
3H), 3.83–4.18 (m, 3H), 5.28 (m, 1H), 6.38 (d, J=7 Hz,
28b: mp 180–182°C; UV (MeOH) umax 257.0 nm; [h]D25
1
−36.36 (c 0.18, MeOH); H NMR (DMSO-d6) l 3.63–