Y. Yoshimura et al. / Bioorg. Med. Chem. 8 (2000) 1545±1558
1551
under re¯ux for 4 h. After the solution was allowed to
cool to room temperature, a CH3CN solution (2 mL) of
8 (108 mg, 0.20 mmol) and SnCl4 (0.40 mL of 1 M
CH2Cl2 solution, 0.40 mmol) was added at 0 ꢀC under
Ar atmosphere. The mixture was stirred at room tem-
perature for 1.5 h and then kept under re¯ux for 3.5 h.
After allowed to cool to room temperature, the mixture
was quenched with saturated NaHCO3. After ®ltration
through a pad of Celite, the ®ltrate was extracted with
CHCl3Â3. The organic phase was washed with brine
and dried (Na2SO4). The ®ltrate was concentrated under
reduced pressure, and the residue was puri®ed by col-
umn chromatography over silica gel (25% AcOEt in
hexane) to give 9a (a/b=2.4/1) (96 mg, 79%) as a foam:
1-(3-O-Benzyl-5-O-(tert-butyldiphenylsilyl)-2-deoxy-2-
¯uoro-4-thio-D-arabino-pentofuranosyl)-5-(E)-(2-bromovi-
nyl)uracil (9d). From 8 (128 mg, 0.237 mmol), 9d was
obtained as described in the synthesis of 9a. The residue
was puri®ed by column chromatography over silica gel
(17% AcOEt in hexane) to give 9d (a/b=2.2/1) (124 mg,
1
75%) as a foam: UV lmax (MeOH) 295, 251 nm; H
NMR (CDCl3) d 8.11 (0.31H, br s, D2O exchangeable),
8.05 (0.69H, br s, D2O exchangeable), 7.78 (0.69H, s),
7.62±7.67 (4.31H, m), 7.16±7.52 (12H, m), 6.56 (0.31H,
dd, J=21.5, 3.9 Hz), 6.55 (0.31H, d, J=14.2 Hz), 6.31
(0.69H, dd, J=16.1, 2.0 Hz), 6.30 (0.69H, d, J=14.2 Hz),
5.07 (0.69H, dt, J=46.9, 1.8 Hz), 5.03 (0.31H, dt, J=50.3,
3.4 Hz), 4.63 (0.31H, d, J=12.2 Hz), 4.60 (0.31H, d,
J=11.2 Hz), 4.59 (0.69H, d, J=10.3 Hz), 4.52 (0.69H, d,
J=11.2Hz), 4.45 (0.69H, dt, J=10.7, 1.9 Hz), 4.33 (0.31H,
dt, J=10.3, 2.4 Hz), 3.65±3.97 (3H, m), 1.09 (6.21H, s),
1.08 (2.79H, s); FAB±MS m/z 695, 697 (M++H).
1
UV lmax (MeOH) 266 nm; H MMR (CDCl3) d 8.24
(0.29H, br s, D2O exchangeable), 8.20 (0.71H, br s, D2O
exchangeable), 7.62±7.70 (4H, m), 7.59 (0.71H, d,
J=1.0 Hz), 7.55 (0.29H, d, J=1.0 Hz), 7.17±7.50 (11H,
m), 6.56 (0.29H, dd, J=22.5, 4.4 Hz), 6.31 (0.71H, dd,
J=16.6, 2.9 Hz), 5.08 (0.71H, dt, J=47.9, 2.9 Hz), 5.03
(0.29H, dt, J=51.0, 3.0 Hz), 4.64 (0.29H, d, J=11.2 Hz),
4.60 (0.29H, d, J=11.7 Hz), 4.59 (0.71H, d, J=11.7 Hz),
4.56 (0.71H, d, J=11.2 Hz), 4.39 (0.71H, dt, J=11.2,
3.4 Hz), 4.35 (0.29H, dt, J=10.8, 2.9 Hz), 3.60±3.91 (3H,
m), 1.85 (0.87H, d, J=1.0 Hz), 1.73 (2.13H, d, J=1.5
Hz), 1.08 (6.39H, s), 1.07 (2.61H, s); FAB±MS m/z 605
(M++H).
1-(3-O-Benzyl-5-O-(tert-butyldiphenylsilyl)-2-deoxy-2-
¯uoro-4-thio-D-arabino-pentofuranosyl)-5-(2-hydroxy-
ethyl)uracil (9e). From 8 (258 mg, 0.48 mmol), 9e was
obtained as described in the synthesis of 9a. The residue
was puri®ed by column chromatography over silica gel
(60% AcOEt in hexane) to give 9e (a/b=1.9/1) (216 mg,
1
71%) as a foam: UV lmax (MeOH) 267 nm; H NMR
(CDCl3) d 8.11 (0.34H, br s, D2O exchangeable), 8.08
(0.66H, br s, D2O exchangeable), 7.73 (0.66H, s), 7.57±
7.69 (4.34H, m), 7.18±7.49 (11H, m), 6.55 (0.34H, dd,
J=22.2, 4.5 Hz), 6.29 (0.66H, dd, J=16.6, 2.4 Hz), 5.09
(0.66H, dt, J=47.4, 2.4 Hz), 5.04 (0.34H, dt, J=50.8,
3.3 Hz), 4.64 (0.34H, d, J=12.5 Hz), 4.60 (0.34H, d,
J=11.7 Hz), 4.59 (0.69H, d, J=11.7 Hz), 4.55 (0.66H, dt,
J=11.2 Hz), 4.40 (0.66H, dt, J=11.2, 2.4 Hz), 4.34
(0.34H, dt, J=10.1, 2.2 Hz), 3.62±3.93 (3.68H, m), 3.56
(1.32H, q, J=5.9 Hz), 2.49 (0.68H, m, D2O exchange-
able), 2.36 (1.32H, t, J=5.9 Hz), 2.10 (0.34H, t, J=5.4Hz,
D2O exchangeable), 2.07 (0.66H, t, J=5.9 Hz, D2O
exchangeable), 1.07 (5.94H, s), 1.06 (3.06H, s); FAB±MS
m/z 635 (M++H).
1-(3-O-Benzyl-5-O-(tert-butyldiphenylsilyl)-2-deoxy-2-
¯uoro-4-thio-D-arabino-pentofuranosyl)-5-ethyluracil
(9b). From 8 (780 mg, 1.45 mmol), 9b was obtained as
described in the synthesis of 9a. The residue was puri®ed
by column chromatography over silica gel (25% AcOEt
in hexane) to give 9b(a/b=2.2/1) (609mg, 68%) as a foam:
UV lmax (MeOH) 266nm; 1H NMR (CDCl3) d 7.98
(0.31H, br s, D2O exchangeable) 7.95 (0.69H, br s, D2O
exchangeable), 7.55±7.69 (5H, m), 7.18±7.50 (11H, m), 6.57
(0.31H, dd, J=23.0, 4.4 Hz), 6.31 (0.69H, dd, J=17.1,
2.4 Hz), 5.08 (0.69H, dt, J=48.3, 2.9 Hz), 5.04 (0.31H, ddd,
J=50.6, 3.7, 2.9 Hz), 4.64 (0.31H, d, J=11.6 Hz), 4.60
(0.31H, d, J=11.1 Hz), 4.59 (1.38H, s), 4.39 (0.69H, dt,
J=11.7, 2.9 Hz), 4.34 (0.31H, dt, J=10.3, 2.4Hz), 3.62±
3.90 (3H, m), 2.12±2.32 (2H, m), 1.07 (6.21H, s), 1.06
(2.79H, s), 1.04 (0.93H, t, J=7.3Hz), 0.96 (2.07H, t,
J=7.3 Hz); FAB±MS m/z 619 (M++H).
1-(3-O-Benzyl-5-O-(tert-butyldiphenylsilyl)-2-deoxy-2-
¯uoro-4-thio-D-arabino-pentofuranosyl)-5-¯uorouracil
(9f). From 8 (769 mg, 1.43 mmol), 9f was obtained as
described in the synthesis of 9a. The residue was puri®ed
by column chromatography over silica gel (25% AcOEt
in hexane) to give 9f (a/b=2.1/1) (687 mg, 79%) as a
1-(3-O-Benzyl-5-O-(tert-butyldiphenylsilyl)-2-deoxy-2-
¯uoro-4-thio-D-arabino-pentofuranosyl)-5-iodouracil (9c).
From 8 (427 mg, 0.794 mmol), 9c was obtained as
described in the synthesis of 9a. The residue was puri®ed
by column chromatography over silica gel (25% AcOEt
in hexane) to give 9c (a/b=1.9/1) (443 mg, 78%) as a
1
foam: UV lmax (MeOH) 271 nm; H NMR (CDCl3) d
8.26 (0.32H, br s, D2O exchangeable), 8.22 (0.68H, br s,
D2O exchangeable), 8.00 (0.68H, d, J=6.8 Hz), 7.89
(0.32H, dd, J=6.4, 2.0 Hz), 7.60±7.67 (4H, m), 7.15±7.49
(11H, m), 6.51 (0.32H, ddd, J=20.9, 3.7, 0.9 Hz), 6.24
(0.68H, d, J=15.1 Hz), 5.05 (0.68H, dt, J=47.4, 2.4 Hz),
5.04 (0.32H, dt, J=51.3, 3.9 Hz), 4.64 (1H, d, J=11.2 Hz),
4.53 (1H, d, J=11.7 Hz), 4.40 (0.68H, dt, J=10.7,
2.4 Hz), 4.34 (0.32H, dt, J=10.3, 3.4 Hz), 3.60±3.94
(3H, m), 1.08 (2.88H, s), 1.07 (6.12H, s); FAB±MS m/z
609 (M++H).
1
foam: UV lmax (MeOH) 289 nm; H NMR (CDCl3) d
8.32 (0.34H, br s, D2O exchangeable), 8.27 (1H, s, D2O
exchangeable), 8.13 (0.66H, br s), 7.60±7.69 (4H, m), 7.21±
7.50 (11H, m), 6.52 (0.34H, dd, J=23.0, 3.9 Hz), 6.22
(0.66H, dd, J=15.1, 2.0 Hz), 5.06 (0.66H, dt, J=46.9,
1.7 Hz), 5.01 (0.34H, dt, J=51.2, 2.3 Hz), 4.64 (0.34H, d,
J=11.2 Hz), 4.63 (0.66H, d, J=11.2 Hz), 4.57 (0.34H, d,
J=11.7 Hz), 4.53 (0.66H, d, J=11.7 Hz), 4.42 (0.66H, dt,
J=11.2, 1.8 Hz), 4.34 (0.34H, dt, J=10.0, 1.8 Hz), 3.73±
3.97 (2H, m), 3.64±3.72 (1H, m), 1.08 (3.06H, s), 1.07
(5.94H, s); FAB±MS m/z 717 (M++H).
1-(3-O-Benzyl-5-O-(tert-butyldiphenylsilyl)-2-deoxy-2-
¯uoro-4-thio-D-arabino-pentofuranosyl)-5-¯uorocytosine
(9g). From 8 (764 mg, 1.42 mmol), 9g was obtained as
described in the synthesis of 9a. The residue was puri®ed