S.-C. Hung et al.
FULL PAPER
n˜ =2880, 2113, 1746, 1724, 1289 cmꢀ1
;
1H NMR (400 MHz, CDCl3): d=
J=5.0, 1H, 1-OH); 13C NMR (100 MHz, CDCl3): d = 166.22 (C), 165.41
(C), 136.61 (C), 133.54 (CH), 133.28 (CH), 129.89 (C), 129.76 (CH),
129.33 (C), 128.58 (CH), 128.45 (CH), 128.24 (CH), 128.12 (CH), 96.35
(CH), 75.72 (CH), 74.88 (CH2), 74.73 (CH), 73.49 (CH), 65.56 (CH),
62.97 (CH2); HRMS (FAB): calcd for C27H25N3O7Na: 526.1593; found:
526.1570 [M+Na+]; elemental analysis calcd (%) for C27H25N3O7: C
64.41, H 5.00, N 8.35; found: C 64.24, H 4.91, N 8.00.
8.11 8.08 (m, 4H, Bz-H), 7.64 7.56 (m, 2H, Bz-H), 7.49 7.44 (m, 4H,
Bz-H), 7.40 7.37 (m, 2H, Ph-H), 7.31 7.28 (m, 3H, Ph-H), 5.98 (d, J=
8.4 Hz, 1H, H-1), 5.58 (t, J=9.6 Hz, 1H, H-3), 5.51 (s, 1H, PhCH), 4.42
(dd, J=15.9, 10.3 Hz, 1H, H-6a), 4.40 (dd, J=9.6, 8.4 Hz, 1H, H-2), 3.88
(dt, J=9.6, 1.7 Hz, 1H, H-4), 3.80 (m, 2H, H-5, H-6b); 13C NMR
(100 MHz, CDCl3): d = 165.17 (C), 164.22 (C), 136.51 (C), 134.07 (CH),
133.44 (CH), 130.09 (CH), 129.90 (CH), 129.24 (C), 129.09 (CH), 128.64
(CH), 128.47 (CH), 128.40 (C), 128.19 (CH), 126.08 (CH), 101.62 (CH),
93.89 (CH), 78.56 (CH), 71.85 (CH), 68.27 (CH2), 67.26 (CH), 64.18
(CH); HRMS (FAB): calcd for C27H23N3O7: 502.1615; found: 502.1624
[M+H+]; elemental analysis calcd (%) for C27H23N3O7: C 64.67, H 4.62,
N 8.38; found: C 64.55, H 4.51, N 8.17.
1,6-Anhydro-4-O-(2-azido-4-O-benzyl-2-deoxy-3,6-di-O-benzoyl-a-d-glu-
copyranosyl)-2-O-benzoyl-3-O-benzyl-b-l-idopyranoside (70): A mixture
of 69 (0.47 g, 0.93 mmol) and freshly dried 4 ä molecular sieves (3 g) in
dichloromethane (4.7 mL) was stirred at room temperature for 30 min
under nitrogen. Anhydrous potassium carbonate (0.20 g, 1.4 mmol) and
trichloroacetonitrile (0.93 mL, 9.27 mmol) were sequentially added to the
mixture at ꢀ788C, and the reaction was gradually warmed up to room
temperature. After stirring for 2 h, the resulting mixture was filtered
through Celite, and the filtrate was washed with water, dried over
MgSO4, filtered, and concentrated in vacuo to give the crude trichloroa-
cetimidate derivative (0.51 g, 84%, a/b 1:4 determined by the 1H NMR
spectrum), which was directly used for subsequent reaction without fur-
ther purification.
2-Azido-3-O-benzoyl-4-O-benzyl-2-deoxy-b-d-glucopyranosyl benzoate
(68): A 1m solution of BH3/THF complex in THF (1.6 mL, 1.6 mmol)
was added at 08C under nitrogen to a mixture of 67 (100 mg, 0.20 mmol)
in dichloromethane (2 mL). After 10 min, TMSOTf (18 mL, 0.10 mmol)
was added to the solution, the ice-bath was removed, and the mixture
was kept stirring for 3 h. The reaction was quenched by triethylamine
(50 mL) followed by slow addition of methanol at 08C, till the evolution
of hydrogen gas stopped. The resulting mixture was coevaporated with
methanol, and the residue was purified through flash column chromatog-
raphy (EtOAc/Hex 1:3) to give the 6-alcohol 68 (88.4 mg, 88%) as a
white solid. [a]3D0 =+46.3 (c=1.0, CHCl3); m.p. 137 1388C; IR (CHCl3):
A mixture of this crude trichloroacetimidate (374 mg, 0.58 mmol), com-
pound 53 (138 mg, 0.39 mmol), and freshly dried 4 ä molecular sieves
(1.5 g) in dichloromethane (5 mL) was stirred at room temperature for
30 min under nitrogen. The reaction flask was cooled to ꢀ788C, trime-
thylsilyl trifluoromethanesulfonate (50 mL, 0.30 mmol) was added to the
mixture, and the resulting solution was gradually warmed up to room
temperature and kept stirring overnight. The reaction was quenched with
triethylamine (100 mL), the mixture was filtered through Celite, the fil-
trate was concentrated in vacuo, and the residue was purified by flash
column chromatography (EtOAc/Hex 1:5) to afford 70 (189 mg, 58%)
and its corresponding b-isomer (52 mg, 16%). [a]3D0 =+74.4 (c=0.5,
CHCl3); m.p. 185 1868C; IR (CHCl3): n˜ =3245, 2097, 1690, 1612, 1504,
n˜ =3372, 2950, 2097, 1720, 1646, 1538, 1259, 1082 cmꢀ1
;
1H NMR
(400 MHz, CDCl3): d=8.09 8.04 (m, 4H, Bz-H), 7.62 7.58 (m, 2H, Bz-
H), 7.48 7.44 (m, 4H, Bz-H), 7.17 7.12 (m, 5H, Ar-H), 5.87 (d, J=
8.4 Hz, 1H, H-1), 5.49 (dd, J=10.2, 9.2 Hz, 1H, H-3), 4.59 (s, 2H,
CH2Ph), 3.95 3.91 (m, 2H, H-4, H-6a), 3.85 (dd, J=9.2, 8.4 Hz, 1H, H-
2), 3.70 (m, 1H, H-5), 3.65 (d, J=8.1 Hz, 1H, H-6b), 1.77 (s, 1H, 6-OH);
13C NMR (100 MHz, CDCl3): d= 137.01 (C), 133.99 (CH), 133.51 (CH),
130.09 (CH), 129.87 (CH),129.11 (C), 128.63 (CH), 128.56 (CH), 128.41
(CH), 128.21 (CH), 128.05 (CH), 93.61 (CH), 76.25 (CH), 74.80 (CH2),
74.70 (CH), 63.39 (CH), 61.01 (CH2).
1268, 1106 cmꢀ1
;
1H NMR (500 MHz, CDCl3): d=8.10 (dd, J=8.5,
1.4 Hz, 2H, Bz-H), 8.05 (dd, J=8.5, 1.4 Hz, 2H, Bz-H), 8.02 (dd, J=8.5,
1.3 Hz, 2H, Bz-H), 7.62 7.55 (m, 3H, Ar-H), 7.49 7.42 (m, 6H, Ar-H),
7.22 7.10 (m, 10H, Ar-H), 5.85 (dd, J=10.8, 9.2 Hz, 1H, H-3’), 5.53 (d,
J=1.7 Hz, 1H, H-1), 5.45 (d, J=3.8 Hz, 1H, H-1’), 5.06 (dd, J=8.0,
1.7 Hz, 1H, H-2), 4.79 (d, J=10.8 Hz, 1H, CH2Ph), 4.74 (d, J=10.8 Hz, 1
H, CH2Ph), 4.64 4.50 (m, 5H, 2îCH2Ph, H-6a, H-6a’, H-6b’), 4.24 (d,
J=7.9 Hz, 1H, H-6b), 4.17 (t, J=8.0 Hz, 1H, H-3), 4.12 4.09 (m, 2H, H-
4, H-5’), 3.81 (dd, J=7.9, 5.0 Hz, 1H, H-5), 3.76 (t, J=9.2, 1H, H-4’),
3.37 (dd, J=10.8, 3.8 Hz, 1H, H-2’); 13C NMR (125 MHz, CDCl3): d =
166.14 (C), 165.71 (C), 165.46 (C), 137.70 (C), 136.47 (C), 133.61 (CH),
133.45 (CH), 133.38 (CH), 129.88 (CH), 129.62 (CH), 129.54 (C), 129.31
(C), 129.25 (C), 128.60 (CH), 128.52 (CH), 128.50 (CH), 128.31 (CH),
127.81 (CH), 127.70 (CH), 99.43 (CH), 99.34 (CH), 79.80 (CH), 77.54
(CH), 77.24 (CH), 76.40 (CH), 75.31 (CH2), 74.90 (CH2), 74.28 (CH),
72.53 (CH), 69.75 (CH), 65.84 (CH2), 63.18 (CH2), 61.42 (CH).
2-Azido-4-O-benzyl-2-deoxy-3,6-di-O-benzoyl-d-glucopyranose
(69):
Benzoyl chloride (54 mL, 0.44 mmol) was slowly added to a solution of 68
(147 mg, 0.29 mmol) in pyridine (1.5 mL) at 08C under nitrogen. The ice-
bath was removed, and the mixture was kept stirring at room tempera-
ture for 1.5 h. Methanol (5 mL) was added to quench the reaction, and
the resulting solution was evaporated under reduced pressure. Water
(2 mL) was added to the solid residue, and the mixture was extracted
with ethyl acetate (3î3 mL). The combined organic layers were sequen-
tially washed with aq 1n HCl, aq sat NaHCO3, and finally with brine.
The organic portion was dried over anhydrous MgSO4, filtered, and con-
centrated in vacuo, and the resulting residue was purified by flash
column chromatography (EtOAc/Hex 1:6) to provide the 1,3,6-triben-
zoate (158 mg, 89%). [a]D30 =ꢀ26.1 (c=1.0, CHCl3); IR (CHCl3): n˜ =
2921, 2106, 1725, 1597, 1494, 1259, 1062 cmꢀ1 1H NMR (400 MHz,
;
CDCl3): d=8.07 8.02 (m, 6H, Bz-H), 7.67 7.54 (m, 3H, Bz-H), 7.44 7.38
(m, 6H, Bz-H), 7.06 7.05 (m, 5H, Ar-H), 5.92 (d, J=8.4 Hz, 1H, H-1),
5.55 (dd, J=10.1, 8.8 Hz, 1H, H-3), 4.63 4.57 (m, 2H, H-6a, H-6b), 4.57
(d, J=10.8, 1H, CH2Ph), 4.52 (d, J=10.8, 1H, CH2Ph), 4.02 3.90 (m, 3
H, H-2, H-4, H-5); 13C NMR (100 MHz, CDCl3): d = 66.03 (C), 165.25
(C), 164.25 (C), 136.51 (C), 133.90 (CH), 133.61 (CH), 133.17 (CH),
130.12 (CH), 129.90 (CH), 129.77 (CH), 129.53 (CH), 129.22 (C), 128.61
(CH), 128.56 (CH), 128.41 (CH), 128.26 (CH), 128.14 (CH), 93.56 (CH),
75.39 (CH), 74.86 (CH2), 74.16 (CH), 63.73 (CH), 62.76 (CH2); HRMS
(FAB): calcd for C36H29N3O8: 608.2034; found: 608.2053 [M+H+].
6-O-Acetyl-4-O-(2-azido-4-O-benzyl-2-deoxy-3,6-di-O-benzoyl-a-d-glu-
copyranosyl)-2-O-benzoyl-3-O-benzyl-l-idopyranosyl acetate (71): Tri-
fluoroacetic acid (0.64 mL) at room temperature under nitrogen was
added to a solution of 70 (159 mg, 0.19 mmol) in acetic anhydride
(3.2 mL). After stirring for 24 h, the reaction was quenched by aq sat
NaHCO3 (10 mL), and the mixture was extracted with EtOAc (3î
10 mL). The combined organic layers were washed with brine, dried over
MgSO4, filtered, and concentrated in vacuo. Purification of the residue
via flash column chromatography (EtOAc/Hex 1:3) yielded the diacetate
71 (160 mg, 89%). [a]3D0 =+75.1 (c=1.0, CHCl3); 1H NMR (400 MHz,
CDCl3): d=8.11 8.03 (m, 13H, Bz-H), 7.62 7.58 (m, 5H, Bz-H), 7.54
7.41 (m, 16H, Bz-H), 7.32 7.24 (m, 3H, Ar-H), 7.17 7.12 (m, 10H, Ar-
H), 6.36 (d, J=3.3 Hz, 1H, H-1b), 6.23 (d, J=2.8 Hz, 1H, H-1a), 5.80
(dd, J=10.6 Hz, 9.0 Hz, 1H, H-3’b), 5.75 (dd, J=10.6, 9.1 Hz, 1H, H-
3’a), 5.31 (d, J=3.7 Hz, 1H, H-1’b), 5.27 (dd, J=11.1, 3.3 Hz, 1H, H-2b),
5.24 (t, J=3.5 Hz, 1H, H-2a), 5.01 (d, J=3.7 Hz, 1H, H-1’a), 4.87 4.83
(m, 3H), 4.63 4.50 (m, 13H), 4.40 4.33 (m, 2H), 4.26(ddd, J=5.8, 3.6,
2.1 Hz, 1H, H-6’b), 4.21 (ddd, J=6.4, 4.2, 2.2 Hz, 1H, H-6’a), 4.16 (t, J=
3.9 Hz, 1H, H-3), 3.98 (t, J=3.1 Hz, 1H, H-4), 3.94(s, 2H), 3.45 (dd, J=
10.7, 3.7 Hz, 1H, H-2’a), 3.38 (dd, J=10.1, 3.7 Hz, 1H, H-2’b), 2.15 (s, 3
H), 2.15 (s, 3H), 2.11 (s, 3H), 2.09 (s, 3H); 13C NMR (100 MHz, CDCl3):
d = 170.76 (C), 169.04 (C), 168.95 (C), 166.12 (C), 165.66 (C), 165.23
(C), 137.22 (C), 136.64 (C), 133.52 (CH), 133.42 (CH), 133.33 (CH),
Ammonia gas was passed through a solution of the 1,3,6-tribenzoate
(27 mg, 44 mmol) in a mixed solvent (THF/MeOH 7:3, 1.4 mL) at 08C for
20 min. The reaction was monitored by TLC till the consumption of start-
ing material (ca. 1.5 h). The solvent was concentrated under reduced
pressure, and the residue was purified by flash column chromatography
(EtOAc/Hex 1:3) to afford 69 (19.5 mg, 87%, a/b 3:1). Recrystallization
of the white solid via vapor diffusion method produced 69b as colorless
crystals. [a]2D9 =+46.9 (c=1.0, CHCl3); IR (CHCl3): n˜ =3435, 2901, 2106,
1720, 1601, 1582, 1263, 1091 cmꢀ1 1H NMR (400 MHz,CDCl3): d=8.10
;
8.01 (m, 4H, Bz-H), 7.60 7.56 (m, 2H, Bz-H), 7.49 7.43 (m, 4H, Bz-H),
7.15 7.07 (m, 5H, Ph-H), 5.92 (dd, J=10.3, 9.0 Hz, 1H, H-3), 5.42 (dd,
J=8.0, 5.0 Hz, 1H, H-1), 4.85 4.36 (m, 4H, 2îCH2Ph, H-6a, H-6b),
3.85 3.79 (m, 2H, H-4, H-5), 3.55 (dd, J=10.3, 8.0 Hz, 1H, H-2), 3.41 (d,
412
¹ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2004, 10, 399 415