2-(N-Acetylamino)-2-deoxy-C-glucopyranosyl Nucleosides
J . Org. Chem., Vol. 65, No. 4, 2000 983
EtOAc, washed (H2O), dried (MgSO4), filtered, and concen-
trated. The crude product was chromatographied (1:1 hex-
anes-EtOAc) to give 11 as an oil (892 mg, 95%): [R]D +118 (c
75.00, 75.15, 75.29, 78.86, 79.83, 80.02, 89.78, 91.37, 92.01,
102.54, 127.77, 127.97, 128.20, 128.41, 128.57, 137.41, 140.75,
141.39, 141.88, 150.23, 163.51, 170.39, 170.80, 172.65. Anal.
Calcd for C56H59N3O14: C, 67.39; H, 5.96; N, 4.21. Found: C,
67.70; H, 5.84; N, 4.08.
1
1, CH2Cl2); H NMR (250 MHz, CDCl3) δ 3.50 (dd, 1 H, J )
13.6, 2.3 Hz), 3.74 (dd, 1 H, J ) 13.6, 2.9 Hz), 3.81 (dd, 1 H, J
) 7.7, 5.1 Hz), 3.98 (dd, 1 H, J ) 5.1, 2.2 Hz), 4.23 (td, 1 H, J
) 7.7, 3.0 Hz), 4.31 (d, 1 H, J ) 11.6 Hz), 4.60 (d, 1 H, J )
11.6 Hz), 4.70 (s, 2 H), 5.62 (d, 1 H, J ) 8.2 Hz), 5.84 (d, 1 H,
J ) 2.1 Hz), 7.19-7.32 (m, 10 H), 7.43 (d, 1 H, J ) 8.2 Hz),
8.89 (s, 1 H). 13C NMR (62.9 MHz, CDCl3) δ 48.89, 70.11, 70.44,
73.25, 76.48, 77.83, 87.86, 100.36, 125.86, 126.11, 126.16,
126.34, 126.50, 127.88, 134.97, 135.16, 137.93, 148.19, 161.80.
Anal. Calcd for C23H23N5O5: C, 61.46; H, 5.16; N, 15.58.
Found: C, 61.88; H, 5.31; N, 15.74.
5′-Am in o-2′,3′-d i-O-ben zyl-5′-d eoxyu r id in e (6b). To a
stirred suspension of 11 (892 mg, 1.987 mmol) in iPrOH (3
mL) were added HS(CH2)3SH (40 µL, 0.4 mmol), Et3N (553
µL, 3.974 mmol), and NaBH4 (151 mg, 3.974 mmol) . After
stirring at 70 °C for 2 h, solvent was evaporated. The residue
was diluted with CH2Cl2, washed with H2O, dried (MgSO4),
filtered, and concentrated. The crude product was chromatog-
raphied (9:1 to 1:1 CH2Cl2-MeOH) to give 6b as white solid
(504 mg, 60%): mp 95 °C, [R]D +46.5 (c 0.65, MeOH), 1H NMR
(250 MHz, CDCl3) δ 2.86 (dd, 1 H, J ) 14.1, 4.4 Hz), 3.08 (dd,
1 H, J ) 14.1, 3.2 Hz), 3.50 (s, 2 H), 3.86 (dd, 1 H, J ) 7.4, 5.2
Hz), 4.06 (dd, 1 H, J ) 5.2, 2.4 Hz), 4.16 (m, 1 H), 4.36 (d, 1 H,
J ) 11.8 Hz), 4.55 (d, 1 H, J ) 11.8 Hz), 4.73 (s, 2 H), 5.61 (d,
1 H, J ) 8.1 Hz), 5.85 (d, 1 H, J ) 2.3 Hz), 7.23-7.37 (m, 10
H), 7.69 (d, 1 H, J ) 8.1 Hz), 8.89 (s, 1 H). 13C NMR (62.9
MHz, CDCl3) δ 41.65, 71.50, 71.62, 76.17, 78.32, 82.07, 89.30,
101.66, 127.30, 127.45, 127.73, 127.91, 136.82, 140.17, 149.88,
163.58. Anal. Calcd for C23H25N3O5: C, 65.24; H, 5.95; N, 9.92.
Found: C, 65.50; H, 6.03; N, 9.70.
P r ep a r a tion of Ester 12. The acid 5 (40 mg, 0.072 mmol)
was dissolved in dry CH2Cl2 (1 mL), and to this solution,
stirred at - 10 °C under Ar atmosphere, were added EtOCOCl
(12 µL, 0.130 mmol) and Et3N (15 µL, 0.108 mmol). The
reaction mixture was stirred at -10 °C for 20 min, and alcohol
6a (30 mg, 0.072 mmol) and DMAP (cat.) were then introduced.
The mixture was stirred 48 h at room temperature and then
diluted in CH2Cl2, washed with H2O, dried (MgSO4), filtered,
concentrated and purified by preparative TLC (1:3 hexanes-
EtOAc) to afford 12 as white solid (40 mg, 58%): mp 65 °C,
[R]D +38.4 (c 0.68, CH2Cl2); 1H NMR (250 MHz, CDCl3) δ 1.82
(s, 3 H), 2.31 (m, 2 H), 3.46-3.66 (m, 4 H), 3.75-3.82 (m, 1
H), 3.86 (dd, 1 H, J ) 7.0, 5.2 Hz), 4.00 (m, 1 H), 4.01 (dd, 1
H, J ) 5.0, 2.3 Hz), 4.08-4.14 (m, 1 H), 4.24-4.59 (m, 10 H),
4.72 (s, 2 H), 5.65 (d, 1 H, J ) 8.3 Hz), 5.82 (d, 1 H, J ) 16.4
Hz), 5.83 (d, 1 H, J ) 2.4 Hz), 6.66 (d, 1 H, J ) 9.7 Hz), 6.94
(td, 1 H, J ) 15.5, 7.6 Hz), 7.22-7.29 (m, 26 H). 13C NMR (62.9
MHz, CDCl3) δ 23.89, 35.06, 48.22, 62.67, 67.48, 67.94, 72.34,
72.55, 72.73, 72.92, 73.19, 73.72, 74.68, 75.33, 75.52, 79.07,
80.32, 90.14, 102.79, 122.73, 128.16, 128.36, 128.64, 128.96,
129.06, 137.52, 127.70, 137.79, 137.87, 138.54, 140.04, 147.31,
P r ep a r a tion of Am id e 14. To a solution of 5b (110 mg,
0.152 mmol) in dry DMF (5 mL) were added 6b (64 mg, 0.152
mmol) and DMAP (1.5 mg). After 2 days stirring at room
temperature, the solvent was evaporated and the residue
purified by preparative TLC (1:9 MeOH-CH2Cl2) to give 14
as white solid (131 mg, 94%): mp 227 °C, [R]D -39.0 (c 1, CH2-
Cl2); 1H NMR (250 MHz, CDCl3) δ 1.86 (s, 3 H), 2.30 (m, 2 H),
3.44 (m, 1 H), 3.67 (m, 2 H), 3.85 (m, 1 H), 4.12 (m, 1 H), 4.24
(m, 1 H), 4.34-4.58 (m, 12 H), 4.71 (d, 1 H, J ) 12.0 Hz), 5.20
(d, 1 H, J ) 4.0 Hz), 5.55 (d, 1 H, J ) 8.0 Hz), 5.89 (d, 1 H, J
) 15.7 Hz), 6.62 (m, 1 H), 6.76 (d, 1 H, J ) 8.4 Hz), 6.79 (d, 1
H, J ) 7.9 Hz), 6.90 (m, 1 H), 7.14-7.30 (m, 25 H). 13C NMR
(62.9 MHz, CDCl3) δ 23.56, 34.41, 40.73, 47.21, 66.25, 67.56,
71.89, 72.52, 73.01, 73.33, 74.25, 75.49, 78.65, 82.07, 96.58,
102.86, 127.76, 127.85, 127.93, 128.21, 128.54, 128.65, 128.83,
137.27, 137.49, 137.81, 138.07, 143.24, 150.72, 163.13, 166.66,
170.59. Anal. Calcd for C56H60N4O11: C, 69.69; H, 6.27; N, 5.81.
Found: C, 69.44; H, 6.38; N, 5.89.
P r ep a r a tion of Diol 15. A solution of compound 14 (140
mg, 0.145 mmol) in THF/H2O (8:1, 4 mL) was stirred at room
temperature and treated with NMO (33 mg, 0.282 mmol) and
OsO4 (1% solution in tBuOH, 37 µL). The reaction mixture was
left at room temperature for 72 h before being diluted with a
10% aqueous solution of sodium bisulfite. The resulting
solution was left under stirring for 10 min before extraction
with CH2Cl2 (3 × 15 mL). The combined organic layers were
washed with H2O, dried (MgSO4), filtered, concentrated, and
purified by preparative TLC (19:1 CH2Cl2-MeOH) to afford
pure compound 15 as a mixture of two isomers (67:33, 121
mg, 84%). Further purification led to a pure sample of the
1
major isomer: mp 131 °C, [R]D -11.0 (c 1, CH2Cl2); H NMR
(250 MHz, CDCl3) δ 1.92 (m, 2 H), 2.02 (s, 3 H), 3.55-3.65 (m,
3 H), 3.81 (m, 2 H), 4.05-4.16 (m, 4 H), 4.34-4.40 (m, 5 H),
4.53-4.83 (m, 10 H), 5.70 (d, 1 H, J ) 3.9 Hz), 5.71 (d, 1 H, J
) 8.1 Hz), 6.84 (d, 1 H, J ) 9.6 Hz), 7.20 (d, 1 H, J ) 8.1 Hz),
7.32-7.50 (m, 26 H), 8.82 (s, 1 H). 13C NMR (62.9 MHz, CDCl3)
δ 23.65, 34.90, 40.02, 48.43, 67.08, 67.52, 71.71, 72.35, 72.61,
72.98, 73.40, 73.50, 73.65, 73.93, 74.33, 75.61, 77.05, 78.89,
81.52, 92.53, 103.07, 128.01, 128.25, 128.41, 128.64, 128.94,
142.33, 150.50, 163.56, 170.99, 173.39. Anal. Calcd for
C
56H60N4O13: C, 67.46; H, 6.07; N, 5.62. Found: C, 67.06; H,
6.10; N, 5.51.
Exp er im en ta l P r oced u r e for th e Ca ta lytic Hyd r oge-
n a tion of Com p ou n d s 12 to 15. Compounds 12 to 15 (∼70
mg) were hydrogenated in dry THF (for compounds 12 and
13) or MeOH (for compounds 14 and 15) (2 mL) at atmospheric
pressure over 10% palladium on charcoal (20 mg) for 20 h at
room temperature. The catalyst was filtered off and washed
with THF or MeOH. Concentration of the solution afforded
the desired compound.
150.57, 163.93, 166.10, 170.53. Anal. Calcd for C56H59N3O12
:
C, 70.82; H, 6.66; N, 2.50. Found: C, 70.64; H, 6.82; N, 2.33.
P r ep a r a tion of Diol 13. To a stirred solution of 12 (65 mg,
0.067 mmol) in 2 mL of THF and 1 mL of water were added
Ba(ClO3)2‚H2O (32.5 mg, 0.101 mmol) and OsO4 (1% solution
in tBuOH, 130 µL), and the mixture was left at room temper-
ature for 15 h. The mixture was concentrated to a residue that
was diluted in EtOAc, washed with H2O, dried (MgSO4),
filtered, concentrated, and purified by preparative TLC (19:1
CH2Cl2-MeOH) to afford the title compound (50 mg, 75%) as
a mixture of two isomers (45:55): mp 70-71 °C, [R]D +17.5 (c
0.4, CH2Cl2); 1H NMR (250 MHz, CDCl3) δ 1.70 (m, 2 H), 1.90
and 1.91 (2s, 3 H), 3.44 (m, 1 H), 3.48-3.57 (m, 1 H), 3.69 (m,
1 H), 3.98-4.51 (m, 21 H), 5.57 (d, 0.55 H, J ) 2.2 Hz), 5.59
(dd, 0.55 H, J ) 2.0 and 8.1 Hz), 5.64 (d, 0.45 H, J ) 8.1 Hz),
5.68 (d, 0.55 H, J ) 4.0 Hz), 5.91 (d, 0.45 H, J ) 2.4 Hz), 6.68
(d, 0.45 H, J ) 9.6 Hz), 6.91 (d, 0.55 H, J ) 9.6 Hz), 7.07 (d,
0.55 H, J ) 8.1 Hz), 7.26-7.35 (m, 25 H), 7.47 (d, 0.45 H, J )
8.2 Hz). 13C NMR (62.9 MHz, CDCl3) δ 23.43, 34.29, 48.13,
48.50, 61.33, 62.79, 63.12, 65.38, 66.92, 67.51, 69.83, 71.99,
72.15, 72.34, 72.66, 72.99, 73.18, 73.32, 73.81, 74.01, 74.69,
Ester 1: 93 % yield from 12; mp 124 °C, [R]D +35.0 (c 1,
H2O); 1H NMR (250 MHz, D2O) δ 1.47-1.80 (m, 2 H), 1.93 (t,
3 H, J ) 6.4 Hz), 2.00 (s, 3 H), 2.49 (t, 2 H, J ) 6.4 Hz), 3.38
(dd, 1 H, J ) 8.4, 9.7 Hz), 3.45-3.52 (m, 1 H), 3.64-3.73 (m,
1 H), 3.68 (t, 2 H, J ) 6.4 Hz), 3.80 (dd, 1 H, J ) 2.2, 12.2 Hz),
3.92 (dd, 1 H, J ) 5.7, 10.5 Hz), 3.99-4.06 (m, 1H), 4.30-4.32
(m, 2 H), 4.36 (dd, 1 H, J ) 3.9, 5.1 Hz), 4.42 (d, 1 H, J ) 3.2
Hz), 5.85 (d, 1 H, J ) 3.7 Hz), 5.89 (d, 1 H, J ) 8.1 Hz), 7.74
(d, 1 H, J ) 8.0 Hz), 8.13 (s, 1 H). 13C NMR (62.9 MHz, D2O)
δ 20.60, 22.15, 24.04, 33.42, 53.76, 61.28, 63.80, 69.70, 71.04,
72.81, 73.58, 73.84, 81.58, 90.65, 102.49, 142.08, 151.79,
166.52, 174.68, 176.02. Anal. Calcd for C21H31N3O12: C, 48.74;
H, 6.04; N, 8.12. Found: C, 48.55; H, 6.20; N, 8.01.
Ester 2 (two diastereoisomer): 100 % yield from 13; mp
1
204 °C, [R]D + 30.9 (c 0.7, H2O), H NMR (250 MHz, D2O) δ
1.87-2.01 (m, 2 H), 2.23 (s, 3 H), 3.38-3.45 (m, 1 H), 3.58-
4.52 (m, 13 H), 5.83 and 5.90 (2d, 1 H, J ) 3.6 Hz), 5.88 and
5.89 (2d, 1 H, J ) 8.0 Hz), 7.74 and 7.78 (2d, 0.5 H, J ) 8.5
Hz), 7.86 (d, 1 H, J ) 8.0 Hz), 8.44 (s, 0.25 H). 13C NMR (62.9
MHz, D2O) δ 22.23, 28.37, 53.49, 61.36, 61.45, 64.38, 64.71,