Syntheses of Nucleosides from Carbohydrate Templates
J . Org. Chem., Vol. 65, No. 3, 2000 691
phase HPLC (2% MeOH in water, C-18 column) to 2a (70 mg,
35%) and 2b (24 mg, 12%) as white solids. Data for compound
2a : mp 158-160 °C; [R ]25D +104.2° (c 0.66, MeOH); UV (H2O)
λmax 266.5 nm (ꢀ 11 590, pH 7), 263.5 nm (ꢀ 11 790, pH 11),
267.0 nm (ꢀ 11 910, pH 2); 1H NMR (DMSO-d6) δ 11.38 (s,
1H), 7.55 (d, 1H, J ) 1.2 Hz), 5.93 (d, 1H, J ) 2.7 Hz), 4.82 (t,
1H, J ) 3.0 Hz), 4.09 (m, 1H), 3.52 (m, 2H), 1.84 (m, 1H), 1.82
(s, 3H), 1.75 (m, 1H), 0.90 (m, 1H), 0.55 (m, 1H); 13C NMR
(DMSO-d6) δ 167.3, 154.0, 139.5, 112.1, 87.6, 82.3, 65.0, 21.6,
21.2, 15.6, 5.7; FABMS (m/z) 239 (M + 1)+. Anal. Calcd for
atmosphere for 30 min at room temperature. To the suspension
of the sodium salt of the base was added the chloride 22 in
anhydrous CH3CN (20 mL) or DMF (10 mL), which was
prepared from the acetate 21 (2.23 g, 5.43 mmol) as previously
described, over 20 min at 0 °C. The mixture was stirred for 3
h at rt. After removal of the solvent under reduced pressure,
the resulting residue was dissolved in CH2Cl2 (100 mL),
washed with water (20 mL), and dried on MgSO4. After
removal of the drying agent by filtration, the filtrate was
evaporated to give a residue, which was purified by silica gel
column chromatography (EtOAc:hexanes ) 5:1) to give com-
pound 26 as an anomeric mixture [1.87 g, 68% from 21, â/R )
3/1 (CH3CN); 1.79 g, 65% from 21, â/R ) 5/1 (DMF), deter-
mined by NMR]. Compound 26 was separated by silica gel
column chromatography (cyclohexane:ether ) 3:1 to 1:1) to
give compounds 26a and 26b as syrups. Method 2: To a
solution of the lactol 20 (340 mg, 0.92 mmol) and Ph3P (484
mg, 1.85 mmol) in dry THF (10 mL) was added CCl4 (1 mL).
The mixture was heated at 50 °C for 3 h, during which a white
solid was precipitated and cooled to rt. The clear supernatant
was transferred by syringe, over 15 min at 0 °C, to a solution
of the sodium salt of 6-chloropurine in DMF (10 mL) which
was prepared from 6-chloropurine (280 mg, 1.84 mmol) and
60% NaH (73 mg, 1.84 mmol) as described in method 1. The
mixture was stirred at rt for 3 h. The same workup and
purification used in method 1 afforded compound 26 (306 mg,
66% from 20) with a â/R ratio of 6/1. Data for compound 26a :
C
11H14N2O4: C, 55.45; H, 5.92; N, 11.75. Found: C, 55.52; H,
5.91; N, 11.65. Data for compound 2b: mp 148-150 °C; [R ]25
D
+33.2° (c 0.5, MeOH); UV (H2O) λmax 266.5 nm (ꢀ 11 230, pH
1
7), 264.0 nm (ꢀ 11 650, pH 11), 266.5 nm (ꢀ 11 230, pH 2); H
NMR (DMSO-d6) δ 11.34 (s, 1H), 7.53 (s, 1H), 5.90 (s, 1H),
4.82 (t, 1H, J ) 5.6 Hz), 4.29 (m, 1H), 3.40 (m, 2H), 2.05 (m,
1H), 1.80-1.78 (m, 4H), 0.75 (m, 1H), 0.41 (m, 1H); 13C NMR
(DMSO-d6) δ 167.1, 154.1, 139.8, 112.8, 88.3, 83.0, 65.3, 22.7,
15.5, 8.6; FABMS (m/z) 239 (M + 1)+. Anal. Calcd for
C11H14N2O4: C, 55.45; H, 5.92; N, 11.75. Found: C, 55.17; H,
6.04; N, 11.62.
1-(5-O-ter t-Bu t yld ip h en ylsilyl-2,3-d id eoxy-2,3-en d o-
m et h ylen e-â-D-p en t ofu r a n osyl]u r a cil (25a ) a n d 1-(5-O-
ter t-Bu tyld ip h en ylsilyl-2,3-d id eoxy-2,3-en d o-m eth ylen e-
r-D-p en tofu r a n osyl)u r a cil (25b). An anomeric mixture of
25 (â/R ) 2/1 determined by NMR) was prepared from uracil
(912 mg, 8.14 mmol) and the acetate 21 (1.5 g, 3.65 mmol)
using method 2 used for compound 23, and was separated by
silica gel chromatography (hexanes:EtOAc ) 3:1) to give 25a
(720 mg, 43%) and 25b (310 mg, 18%) as syrups. Data for
compound 25a : UV (MeOH) λmax 262.0 nm; 1H NMR (CDCl3)
δ 8.25 (s, 1H), 7.65 (m, 4H), 7.41-7.35 (m, 7H), 6.01 (d, 1H, J
) 2.5 Hz), 5.59 (d, 1H, J ) 8.1 Hz), 4.36 (m, 1H), 3.80 (m, 2H),
2.07 (m, 1H), 1.85 (m, 1H), 1.05 (s, 9H), 0.64 (m, 1H), 0.56 (m,
1H); FABMS (m/z) 463 (M + 1)+. Data for compound 25b: UV
1
UV (MeOH) λmax 264.0 nm; H NMR (CDCl3) δ 8.76 (s, 1H),
8.30 (s, 1H), 7.69-7.66 (m, 4H), 7.46-7.35 (m, 6H), 6.39 (d,
1H, J ) 2.7 Hz), 4.47 (m, 1H), 3.88 (dd, 1H, J ) 5.1, 10.5 Hz),
3.75 (dd, 1H, J ) 6.0, 10.5 Hz), 2.20 (m, 1H), 2.02 (m, 1H),
1.05 (s, 9H), 0.87 (m, 1H), 0.72 (m, 1H); FABMS (m/z) 505 (M
+ 1)+. Data for compound 26b: UV (MeOH) λmax 264.0 nm; 1H
NMR (CDCl3) δ 8.77 (s, 1H), 8.27 (s, 1H), 7.68-7.64 (m, 4H),
7.45-7.35 (m, 6H), 6.24 (s, 1H), 4.41 (m, 1H), 3.83 (dd, 1H, J
) 5.1, 10.4 Hz), 3.75 (dd, 1H, J ) 6.5, 10.3 Hz), 2.18-2.08 (m,
2H), 1.08 (s, 9H), 0.81 (m, 1H), 0.67 (m, 1H); FABMS (m/z)
505 (M + 1)+.
9-(2,3-Dideoxy-2,3-en do-m eth ylen e-â-D-pen tofu r an osyl)-
6-ch lor o-9H-p u r in e (27a ). Compound 26a (430 mg, 0.85
mmol) was desilylated as described in the preparation of
compounds 1a and 1b, and purified by silica gel column
chromatography (CHCl3:MeOH ) 60:1) to give compound 27a
as a syrup (204 mg, 90%): UV (MeOH) λmax 266.0 nm; 1H NMR
(CDCl3) δ 8.78 (s, 1H), 8.42 (s, 1H), 6.43 (d, 1H, J ) 2.87 Hz),
4.47 (m, 1H), 3.84 (m, 2H), 2.21 (m, 1H), 1.97 (m, 1H), 1.10
(m, 1H), 0.95 (m, 1H); 13C NMR (CDCl3) δ 152.2, 142.7, 134.8,
129.7, 127.7, 84.9, 79.7, 63.3, 26.5 19.2, 3.9; FABMS (m/z) 267
(M + 1)+.
1
(MeOH) λmax 262.0 nm; H NMR (CDCl3) δ 8.71 (s, 1H), 7.67
(m, 4H), 7.46-7.36 (m, 7H), 5.95 (s, 1H), 5.73 (d, 1H, J ) 8.0
Hz), 4.38 (m, 1H), 3.81 (dd, 1H, J ) 5.0, 10.3 Hz), 3.59 (dd,
1H, J ) 6.8, 10.3 Hz), 2.02 (m, 1H), 1.83 (m, 1H), 1.04 (s, 9H),
0.74 (m, 1H), 0.51 (m, 1H); FABMS (m/z) 463 (M + 1)+.
1-(2,3-Did eoxy-2,3-en d o-m eth ylen e-â-D-p en tofu r a n os-
yl)u r a cil (3a ). Compound 25a (400 mg, 0.86 mmol) was
desilylated as described in the preparation of compound 1a ,
purified by silica gel column chromatography (CHCl3:MeOH
) 10:1), and crystallized from EtOAc-MeOH (6:1) to give
compound 3a (180 mg, 93%) as a white solid: mp 147-149
°C; [R ]25 +88.5° (c 0.20, MeOH); UV (H2O) λmax 261.5 nm (ꢀ
D
13 870, pH 7), 260.5 nm (ꢀ 7900, pH 11), 261.5 nm (ꢀ 10 600,
1
pH 2); H NMR (DMSO-d6) δ 11.37 (s, 1H), 7.73 (d, 1H, J )
8.1 Hz), 5.90 (d, 1H, J ) 2.6), 5.57 (d, 1H, J ) 8.0 Hz), 4.81 (t,
1H, J ) 5.7 Hz), 4.11 (m, 1H), 3.49 (m, 2H), 1.87 (m, 1H), 1.75
(m, 1H), 0.77 (m, 2H); 13C NMR (DMSO-d6) δ 171.2, 157.0,
147.2, 105.8, 91.0, 83.9, 66.5, 22.3, 21.9, 7.1; FABMS (m/z) 225
(M + 1)+. Anal. Calcd for C10H12N2O4: C, 53.57; H, 5.39; N,
12.49. Found: C, 53.50; H, 5.42; N, 12.41.
1-(2,3-Did eoxy-2,3-en d o-m eth ylen e-r-D-p en tofu r a n os-
yl)u r a cil (3b). Compound 3b (91 mg, 92%) was prepared as
a white solid from 25b (200 mg, 0.43 mmol) using the same
conditions as for compound 3a : mp 149-150 °C; [R ]25D +18.0°
(c 0.20, MeOH); UV (H2O) λmax 262.0 nm (ꢀ 13 230, pH 7), 260.5
nm (ꢀ 7260, pH 11), 262.0 nm (ꢀ 10 230, pH 2); 1H NMR
(DMSO-d6) δ 11.40 (s, 1H), 7.71 (d, 1H, J ) 7.9 Hz), 5.88 (s,
1H), 5.60 (d, 1H, J ) 7.9 Hz), 4.82 (t, 1H, J ) 5.6 Hz), 4.22
(m, 1H), 3.39 (m, 2H), 1.99 (m, 1H), 1.81 (m, 1H), 0.70 (m,
1H), 0.46 (m, 1H); 13C NMR (DMSO-d6) δ 166.7, 154.3, 144.7,
105.1, 88.7, 83.3, 65.4, 22.9, 22.6, 8.7; FABMS (m/z) 225 (M +
1)+. Anal. Calcd for C10H12N2O4: C, 53.57; H, 5.39; N, 12.49.
Found: C, 53.35; H, 5.40; N 12.32.
9-(2,3-Dideoxy-2,3-en do-m eth ylen e-r-D-pen tofu r an osyl)-
6-ch lor o-9H-p u r in e (27b). Compound 27b (97 mg, 91%) was
prepared as a syrup from compound 26b (200 mg, 0.40 mmol)
using the same conditions as for compound 27a : UV (MeOH)
1
λmax 266.0 nm; H NMR (CDCl3) δ 8.83 (s, 1H), 8.33 (s, 1H),
6.26 (s, 1H), 4.83 (t, 1H, J ) 5.6 Hz), 4.32 (m, 1H), 3.45 (m,
2H), 2.19 (m, 1H), 2.10 (m, 1H), 0.81 (m, 1H), 0.61 (m, 1H);
13C NMR (CDCl3) δ 152.3, 142.9, 135.6, 130.1, 127.5, 85.2, 80.1,
63.4, 25.1, 18.6, 5.9; FABMS (m/z) 267 (M + 1)+.
9-(2,3-Did eoxy-2,3-en d o-m eth ylen e-â-D-p en tofu r a n os-
yl)a d en in e (4a ). Compound 27a (177 mg, 0.66 mmol) was
dissolved in MeOH saturated with NH3 (20 mL), and the
resulting solution was stirred for 16 h at 90 °C in a steel bomb.
After removal of the solvent, the yellow residue was triturated
with EtOAc to give a white solid, which was recrystallized from
MeOH to give compound 4a as a white crystal (106 mg, 65%):
mp 192-5 °C; [R ]25 +29.2° (c 0.22, MeOH); UV (H2O) λmax
D
259.0 nm (ꢀ 17 030, pH 7), 258.0 nm (ꢀ 17 230, pH 11), 257.5
1
nm (ꢀ 17 010, pH 2); H NMR (DMSO-d6) δ 8.16 (s, 1H), 8.00
9-(5-O-ter t-Bu t yld ip h en ylsilyl-2,3-d id eoxy-2,3-en d o-
m eth ylen e-â-D-p en tofu r a n osyl)-6-ch lor o-9H-p u r in e (26a )
a n d 9-(5-O-ter t-Bu tyld ip h en ylsilyl-2,3-d id eoxy-2,3-en d o-
m eth ylen e-r-D-pen tofu r an osyl)-6-ch lor o-9H-pu r in e (26b).
Method 1: A mixture of 6-chloropurine (1.88 g, 12.16 mmol)
and NaH (60% in oil, 0.48 g, 12.00 mmol) in anhydrous CH3-
CN (70 mL) or DMF (40 mL) was stirred under a nitrogen
(s, 1H), 7.15 (s, 2H), 6.07 (d, 1H, J ) 2.7 Hz), 4.67 (t, 1H, J )
5.5 Hz), 4.03 (m, 1H), 3.36 (m, 2H), 1.91 (m, 1H), 1.70 (m, 1H),
0.93 (m, 1H), 0.51 (m, 1H); 13C NMR (DMSO-d6) δ 159.0, 155.7,
152.6, 141.6, 121.9, 86.5, 82.5, 64.9, 22.2, 22.0, 6.3; FABMS
(m/z) 248 (M + 1)+. Anal. Calcd for C11H13N5O2: C, 53.43; H,
5.29; N, 28.32. Found: C, 53.52; H, 5.43; N, 28.09.
9-(2,3-Did eoxy-2,3-en d o-m eth ylen e-r-D-p en tofu r a n os-