C-Glycosidic Analogues of Adenophostin A
J . Org. Chem., Vol. 65, No. 14, 2000 4323
was partitioned between AcOEt (100 mL) and H2O (70 mL),
and the organic layer was washed with H2O (70 mL, twice)
and brine (70 mL), dried (Na2SO4), and evaporated. The
residue was purified by column chromatography (SiO2, hexane/
AcOEt 2:1) to give 33 (958 mg, 71% as a white solid): 1H NMR
(CDCl3, 500 MHz) δ 7.35-7.18 (m, 15 H, Ar), 7.02 (m, 2 H,
Ar), 6.87-6.80 (m, 5 H, Ar), 5.83 (d, 1 H, H-1, J ) 3.7), 4.85-
4.48 (m, 9 H, PhCH2), 4.37 (m, 3 H, H-2, H-1′, PhCH2), 4.00
(m, 1 H, H-4), 3.81 (s, 3 H, OCH3), 3.78 (s, 3 H, OCH3), 3.76
(s, 3 H, OCH3), 3.75-3.46 (m, 8 H, H-5a, H-5b, H-2′, H-3′, H-4′,
H-5′, H-6′a, H-6′b), 2.17 (m, 1 H, H-3), 1.93 (m, 1 H, 3-CHaHb),
1.75 (m, 1 H, 3-CHaHb), 1.51 (s, 3 H, CH3), 1.33 (s, 3 H, CH3);
13C NMR (CDCl3, 100 MHz) δ 158.90, 158.88, 158.84, 137.84,
137.76, 130.76, 130.18, 129.68, 129.40, 129.29, 128.14, 127.85,
127.59, 127.41, 127.31, 113.50, 111.05, 104.95, 104.68, 82.06,
80.70, 80.48, 80.37, 80.06, 79.72, 79.59, 77.51, 75.20, 75.16,
74.74, 73.42, 73.33, 72.94, 72.79, 72.60, 71.56, 71.04, 69.08,
68.07, 55.45, 55.37, 55.30, 55.28, 55.20, 55.12, 55.04, 54.94,
40.32, 26.78, 26.69, 26.45, 26.40, 19.87; FAB-HRMS calcd for
(m, 13 H, Ar), 6.23 (s, 1 H, H-1′), 5.73 (d, 1 H, H-2′, J ) 4.6),
5.27 (dd, 1 H, H-3′′, J ) 9.1, 9.1), 4.86 (dd, 1 H, H-4′′, J ) 9.1,
9.1), 4.67-4.47 (m, 4 H, PhCH2), 4.22 (m, 2 H, H-4′, H-1′′),
4.14 (dd, 1 H, H-5′a, J ) 4.5, 12.4), 3.94 (dd, 1 H, H-6′′a, J )
1.9, 11.3), 3.81 (dd, 1H, H-5′b, J ) 1.8, 12.4), 3.74 (m, 2 H,
H-5′′, H-6′′b), 3.68 (dd, 1 H, H-2′′, J ) 5.8, 9.4), 2.99 (m, 1 H,
H-3′), 2.04 (s, 3 H, Ac), 2.02 (s, 3 H, Ac), 2.00 (s, 3 H, Ac), 1.96
(s, 3 H, Ac), 1.89 (m, 1 H, 3′-CHaHb), 1.75 (m, 1 H, 3′-CHaHb);
13C NMR (CDCl3, 100 MHz) δ 170.05, 169.87, 169.18, 169.15,
164.27, 152.30, 150.68, 149.11, 140.87, 136.98, 136.70, 133.33,
132.31, 128.42, 128.36, 128.25, 128.15, 127.87, 127.69, 127.57,
127.51, 127.13, 122.96, 88.64, 83.19, 77.14, 77.05, 75.66, 73.59,
72.58, 71.37, 71.12, 68.60, 68.49, 67.93, 61.78, 36.14, 20.79,
20.65, 20.60, 20.50, 19.56; FAB-HRMS calcd for C46H50N5O13
880.3404 (MH+), found 880.3488. Anal. Calcd for C46H49N5O13
‚
0.5H2O: C, 62.15; H, 5.67; N, 7.88. Found: C, 62.17; H, 5.72;
N, 7.81.
1-[5-O-Ben zyl-3-d eoxy-3-(3-O-ben zyl-4,5,7-tr i-O-a cetyl-
2,6-a n h yd r o-1-d eoxy-D-glycer o-D-id o-h ep t it ol-1-yl)-â-D-
r ibo-p en tofu r a n osyl]u r a cil (36). A suspension of uracil (56
mg, 500 µmol) and (NH4)2SO4 (2 mg, 15 µmol) in HMDS (3
mL) was heated under reflux for 30 min. The resulting clear
solution was evaporated and azeotroped with toluene (three
times). To a mixture of the resulting residue and 34 (50 mg,
71 µmol) in CH3CN (2 mL) was added TMSOTf (90 µL, 497
µmol) at 0 °C, and the mixture was stirred at room tempera-
ture for 4 h. The reaction mixture was partitioned between
AcOEt (40 mL) and aqueous HCl (1 M, 30 mL), and the organic
layer was washed with aqueous HCl (1 M, 30 mL), H2O (30
mL), aqueous NaHCO3 (saturated, 30 mL), and brine (20 mL),
dried (Na2SO4), and evaporated. The residue was purified by
column chromatography (SiO2, CHCl3/AcOEt 1:1) to give 36
(52 mg, 98% as a white amorphous): 1H NMR (CDCl3, 500
MHz) δ 9.12 (br s, 1 H, NH), 7.96 (d, 1 H, H-6, J ) 8.2), 7.45-
7.20 (m, 10 H, Ar), 5.82 (s, 1 H, H-1′), 5.49 (d, 1 H, H-2′, J )
4.7), 5.35 (dd, 1 H, H-5, J ) 2.1, 8.2), 5.25 (dd, 1 H, H-3′′, J )
8.8, 8.8), 4.86 (dd, 1 H, H-4′′, J ) 8.8, 8.8), 4.61-4.48 (m, 4 H,
PhCH2), 4.26 (m, 2 H, H-1′′, H-6′′a), 4.05 (m, 2 H, H-4′, H-6′′b),
3.74 (m, 3 H, H-5′a, H-5′b, H-5′′), 3.64 (dd, 1 H, H-2′′, J ) 5.6,
8.8), 2.56 (m, 1 H, H-3′), 2.05 (s, 3 H, Ac), 2.01 (s, 3 H, Ac),
1.94 (s, 3 H, Ac), 1.91 (s, 3 H, Ac), 1.79 (m, 1 H, 3′-CHaHb),
1.54 (m, 1 H, 3′-CHaHb); 13C NMR (CDCl3, 125 MHz) δ 170.42,
170.39, 169.65, 169.22, 163.23, 149.94, 139.83, 137.41, 137.00,
139.83, 137.41, 137.00, 128.79, 128.52, 128.47, 128.00, 127.90,
127.58, 101.51, 89.88, 83.45, 76.96, 75.64, 73.98, 72.65, 71.16,
70.91, 69.00, 68.73, 67.82, 61.67, 60.39, 35.57, 35.57, 29.68,
20.85, 20.75, 20.60, 20.49, 19.83; FAB-HRMS calcd for
C
53H62O12Na 913.4139 (MNa+), found 913.4178. Anal. Calcd
for C53H62O12: C, 71.44; H, 7.01. Found: C, 71.46; H, 7.11.
5-O-Ben zyl-1,2-d i-O-a cetyl-3-d eoxy-3-(3-O-ben zyl-4,5,7-
tr i-O-acetyl-2,6-an h ydr o-1-deoxy-D-glycer o-D-ido-h eptitol-
1-yl)-r,â-D-r ibo-p en tofu r a n ose (34). A solution of 33 (1.7 g,
1.9 mmol) in aqueous TFA (80%, 10 mL) was stirred at room
temperature for 3 h and then evaporated. The residue was
purified by column chromatography (SiO2, CHCl3/MeOH 50:
1-4:1) to give an oil. A mixture of the oil obtained and NaOMe
(28% in MeOH, 760 µL) in MeOH (10 mL) was stirred at room
temperature for 30 min and then neutralized with Diaion WK
20 (H+ form). The resin was filtered off, and the filtrate was
evaporated. A solution of the resulting residue, Ac2O (1.4 mL,
14.8 mmol), Et3N (2.12 mL, 15 mmol), and DMAP (23 mg, 0.19
mmol) in MeCN (20 mL) was stirred at room temperature for
1 h. The reaction mixture was partitioned between AcOEt (200
mL) and aqueous NaHCO3 (saturated, 150 mL), and the
organic layer was washed with aqueous NaHCO3 (saturated,
150 mL), H2O (150 mL), and brine (100 mL), dried (Na2SO4),
and evaporated. The residue was purified by column chroma-
tography (SiO2, hexane/AcOEt, 2:1) to give 34 (932 mg, 70%
as a white solid): 1H NMR (CDCl3, 500 MHz) δ 7.37-7.23 (m,
10 H, Ar), 6.36 (d, 0.26 H, H-1R, J ) 4.0), 6.09 (s, 0.74 H,
H-1â,), 5.40 (dd, 0.26 H, H-2, J ) 4.0, 6.8), 5.32 (d, 0.74 H,
H-2, J ) 4.4), 5.25 (dd, 1 H, H-3′, J ) 9.3, 9.3), 4.89 (m, 1 H,
H-4′), 4.64-4.48 (m, 4 H, PhCH2), 4.26-4.48 (m, 3 H, H-4,
H-5a, H-1′), 3.94 (m, 1 H, H-5b), 3.77-3.57 (m, 3 H, H-2′, H-5′,
H-6′a, H-6′b), 2.64-2.48 (m, 1 H, H-3), 2.07-1.78 (m, 17 H, 5
× Ac, CH2); 13C NMR (CDCl3, 100 MHz) δ 170.28, 170,21,
169.99, 169.68, 169.56, 169.49, 169.16, 169.02, 155.26, 137.68,
137.59, 137.34, 132.72, 130.78, 129.60, 128.32, 127.85, 127.80,
127.64, 127.57, 127.50, 127.22, 113.42, 110.08, 98.98, 95.31,
82.73, 82.19, 77.20, 76.05, 73.53, 73.33, 72.58, 72.36, 72.29,
71.70, 71.45, 70.17, 68.84, 68.50, 68.21, 62.19, 55.11, 37.92,
34.90, 29.47, 21.39, 20.94, 20.76, 20.63, 20.47, 20.29, 20.22,
19.86; FAB-HRMS calcd for C36H44O14Na 723.2628 (MNa+),
found 723.2632. Anal. Calcd for C36H44O14: C, 61.71; H, 6.33.
Found: C, 61.66; H, 6.38.
C
C
38H45N2O14 753.2870 (MH+), found 753.2866. Anal. Calcd for
38H44N2O14: C, 60.63; H, 5.89; N, 3.72. Found: C, 60.71; H,
6.06; N, 3.55.
N6-Ben zoyl-9-[5-O-b en zyl-3-d eoxy-3-(3-O-b en zyl-7-O-
tr ityl-2,6-a n h yd r o-1-d eoxy-D-glycer o-D-id o-h ep titol-1-yl)-
â-D-r ibo-p en tofu r a n osyl]a d en in e (37). A solution of 35 (224
mg, 255 µmol) and NaOMe (28% in MeOH, 102 µL, 510 µmol)
in MeOH (2 mL) was stirred at 0 °C for 50 min and then
neutralized with Diaion WK 20 (H+ form). The resin was
filtered off, and the filtrate was evaporated. A mixture of the
resulting residue and TrCl (355 mg, 1.27 mmol) in pyridine (2
mL) was stirred at 50 °C for 1 h. The reaction mixture was
partitioned between AcOEt (40 mL) and H2O (30 mL), and the
organic layer was washed with aqueous HCl (1 M, 30 mL),
H2O (30 mL), aqueous NaHCO3 (saturated, 30 mL), and brine
(20 mL), dried (Na2SO4), and evaporated. The residue was
purified by column chromatography (SiO2, CHCl3/EtOH 30:1)
to give 37 (235 mg, 97% as a white amorphous solid): 1H NMR
(CDCl3, 500 MHz) δ 9.03 (br s, 1 H), 8.76 (s, 1H), 8.50 (s, 1 H),
7.86 (d, 2 H, J ) 7.6), 7.62-7.16 (m, 28 H), 6.14 (s, 1 H), 4.67
(m, 2 H), 4.53 (m, 3 H), 4.32 (d, 1 H, J ) 10.0), 4.27 (m, 1 H),
3.87 (m, 1 H), 3.68 (dd, 1 H, J ) 9.1, 9.1), 3.62 (dd, 1 H, J )
2.8, 11.0), 3.53 (m, 2 H), 3.45 (dd, 1 H, J ) 9.1, 9.1), 3.22 (d, 2
H, J ) 3.8), 2.61 (m, 1 H), 2.00 (m, 1 H), 1.72 (m, 1 H); 13C
NMR (CDCl3, 100 MHz) δ 164.12, 151.69, 149.56, 149.07,
143.24, 140.79, 137.12, 137.03, 133.28, 132.36, 128.66, 128.40,
128.28, 128.13, 127.75, 127.62, 127.57, 127.43, 127.34, 126.72,
124.93, 122.79, 91.85, 86.46, 84.13, 78.57, 77.06, 73.12, 72.87,
N6-Ben zoyl-9-[5-O-ben zyl-3-d eoxy-3-(3-O-ben zyl-4,5,7-
tr i-O-acetyl-2,6-an h ydr o-1-deoxy-D-glycer o-D-ido-h eptitol-
1-yl)-â-D-r ibo-p en tofu r a n osyl]a d en in e (35). A suspension
of N6-benzoyladenine (343 mg, 1.43 mmol) in HMDS/pyridine
(4 mL/2 mL) was heated under reflux for 1 h. The resulting
clear solution was evaporated and azeotroped with toluene
(three times). To a mixture of the resulting residue and 34
(251 mg, 358 µmol) in CH3CN (4 mL) was added SnCl4 (209
µL, 1.79 mmol) at 0 °C, and the mixture was stirred at room
temperature for 12 h. The resulting mixture was partitioned
between AcOEt (60 mL) and aqueous HCl (1 M, 50 mL), and
the organic layer was washed with aqueous HCl (1 M, 50 mL),
H2O (50 mL), aqueous NaHCO3 (saturated, 50 mL), and brine
(50 mL), dried (Na2SO4), and evaporated. The residue was
purified by column chromatography (SiO2, CHCl3/EtOH, 60:
1) to give 35 (265 mg, 78% as a white amorphous solid): 1H
NMR (CDCl3, 500 MHz) δ 9.07 (br s, 1 H, NH), 8.81 (s, 1 H,
H-2), 8.51 (s, 1 H, H-8), 8.03 (d, 2 H, Ar, J ) 7.6), 7.62-7.23