200
K. Nishiyama et al. / Bioorg. Med. Chem. 17 (2009) 195–202
ture was stirred for 1 h at 80 °C. Toluene was added and then the
solvents were evaporated in vacuo to give a residue, which was
purified by silica gel column chromatography (hexane/
(1H, dd, J = 10.2 Hz, 2.4 Hz), 3.91 (2H, m), 3.63 (1H, m), 3.59 (1H,
dd, J = 10.8 Hz, 1.8 Hz), 3.49 (2H, m), 2.12 (3H, s), 2.11 (3H, s),
2.05 (3H, s), 1.98 (3H, s), 1.94 (3H, s), 1.91 (3H, s), 1.88 (3H, s),
1.83 (3H, s); 13C NMR (150 MHz, CDCl3) d 170.6, 170.5, 170.2,
169.9, 169.7, 169.6, 169.2, 168.9, 165.9, 165.4, 133.7, 133.6,
129.9, 129.9, 129.0, 128.8, 128.7, 128.5, 99.6, 97.4, 97.0, 75.9,
71.8, 69.7, 69.4, 69.3, 69.2, 68.9, 68.6, 68.3, 66.4, 65.9, 65.8, 65.2,
62.3, 62.1, 60.6, 48.3, 28.8, 20.8, 20.8, 20.7, 20.6, 20.6, 20.5, 20.5;
IR (neat) 2939, 2100, 1749, 1603, 1452, 1371, 1226, 1047, 756,
EtOAc = 1:2) to give 4 (205 mg, 74%). ½a D24
ꢀ7.61 (c = 1.0 in CHCl3);
ꢁ
1H NMR (600 MHz, CDCl3) d 8.14 (2H, m), 8.04 (2H, m), 7.58 (4H,
m), 7.45 (2H, m), 5.58 (1H, t, J = 10.2 Hz), 5.54 (1H, dd, J = 3.6 Hz,
1.8 Hz), 5.45 (1H, m), 5.36 (1H, dd, J = 10.2 Hz, 3.6 Hz), 5.23 (1H,
t, J = 10.2 Hz), 5.20 (1H, dd, J = 3.6 Hz, 1.8 Hz), 5.10 (2H, m), 4.99
(1H, d, J = 1.8 Hz), 4.89 (1H, m), 4.81 (1H, d, J = 1.8 Hz), 4.57 (1H,
dd, J = 10.2 Hz, 3.6 Hz), 4.38 (1H, m), 4.21 (1H, dd, J = 12.0 Hz,
5.4 Hz), 4.10 (4H, m), 3.99 (1H, dd, J = 12.0 Hz, 1.8 Hz), 3.89 (1H,
dd, J = 10.8 Hz, 7.2 Hz), 3.66 (1H, dd, J = 10.8 Hz, 1.8 Hz), 2.13 (3H,
s), 2.12 (3H, s), 2.05 (3H, s), 1.99 (3H, s), 1.98 (3H, s), 1.94 (3H,
s), 1.86 (3H, s), 1.83 (3H, s); 13C NMR (150 MHz, CDCl3) d 171.2,
170.1, 170.1, 170.0, 169.9, 169.8, 169.1, 169.1, 165.9, 165.4,
133.6, 133.6, 130.0, 130.0, 128.7, 128.6, 128.6, 128.5, 99.4, 97.4,
92.2, 74.7, 72.1, 69.6, 69.4, 69.3, 69.2, 69.1, 68.5, 68.4, 66.3, 66.1,
62.4, 62.3, 60.4, 60.4, 21.1, 20.9, 20.8, 20.7, 20.7, 20.6, 20.5, 20.4;
IR (neat) 3470, 3026, 2941, 1745, 1603, 1452, 1371, 1226, 1047,
715 cmꢀ1
;
HRMS (ESI) calcd for C51H61O26N3 [M+Na]+:
1154.3441, found 1154.3429.
4.3.5. Azide derivative 10
The mixture of azide 7 (266 mg, 0.24 mmol) and Pd on C
(130 mg) in THF/EtOH (1:1) was stirred under hydrogen atmo-
sphere at rt for 50 min. The catalyst was filtered off, and the filtrate
was condensed in vacuo to give a crude preparation of 8 as syrup.
The crude 8 and 14-azido-3,6,9,12-tetraoxatetradecanoic acid 929
(0.71 mmol, 195 mg) was dissolved in dry CH2Cl2 (3 ml) at rt. Then,
756, 716 cmꢀ1
;
HRMS (ESI) calcd for C48H56O26 [M+Na]+:
WSCI–HCl (90 mg, 0.47 mmol), DIPEA (130 ll, 0.71 mmol), and
1071.2958, found 1071.2938.
HOBt (0.47 mmol, 64 mg) was added to the mixture. After 12 h,
the mixture was diluted with CH2Cl2, washed with H2O, and the or-
ganic layer was dried, filtered, and concentrated in vacuo. The
crude residue was purified by silica gel chromatography (CH2Cl2/
MeOH = 9:1) to obtain 10 (294 mg, 90%, two steps yield from 7).
4.3.3. 2,3,4,6-tetra-O-acetyl-a-D-mannopyranosyl-(1 ? 3)-
[2,3,4,6-tetra-O-acetyl-
benzoyl- -mannopyranosyl trichloroacetimidate (5)
To a stirred solution of 4 (325 mg, 0.31 mmol) in anhydrous
CH2Cl2 (3 ml) was added trichloroacetonitrile (12.5 l, 1.24 mmol)
and DBU (8.8 l, 0.06 mmol) at 0 °C. The mixture was stirred for 1 h
a-D-mannopyranosyl-(1 ? 6)]-2,4-di-O-
a-D
½
a 2D1 = +6.36 (c = 1.0 in CHCl3); 1H NMR (600 MHz, CDCl3) d 8.15
ꢁ
l
(2H, m), 8.07 (2H, m), 7.63 (1H, m), 7.59 (1H, m), 7.55 (2H, m),
7.46 (2H, m), 7.12 (1H, br m), 5.66 (1H, t, J = 9.6 Hz), 5.49 (1H,
dd, J = 3.0 Hz, 1.8 Hz), 5.34 (1H, dd, J = 10.2 Hz, 3.6 Hz), 5.24 (2H,
m), 5.10 (2H, m), 5.03 (1H, d, J = 1.8 Hz), 5.02 (1H, d, J = 1.8 Hz),
4.87 (1H, dd, J = 3.0 Hz, 1.8 Hz), 4.80 (1H, d, J = 1.8 Hz), 4.46 (1H,
dd, J = 9.6 Hz, 3.0 Hz), 4.09 (3H, m), 4.02 (5H, m), 3.96 (1H, m),
3.90 (1H, m), 3.85 (1H, m), 3.69 (15H, m), 3.58 (2H, m), 3.48 (1H,
m), 3.38 (4H, m), 2.11 (3H, s), 2.10 (3H, s), 2.06 (3H, s), 1.98 (3H,
s), 1.92 (3H, s), 1.90 (3H, s), 1.88 (3H, s), 1.82 (3H, s); 13C NMR
(150 MHz, CDCl3) d 170.6, 170.5, 169.9, 169.9, 169.8, 169.7,
169.6, 169.2, 169.0, 165.9, 165.3, 133.6, 133.5, 129.9, 129.1,
128.8, 128.7, 128.5, 99.5, 97.4, 97.1, 76.1, 71.8, 70.9, 70.6, 70.5,
70.2, 70.0, 70.0, 69.4, 69.4, 69.3, 69.2, 68.9, 68.5, 68.4, 68.3, 66.4,
66.0, 65.9, 65.8, 62.3, 62.1, 53.4, 50.6, 35.9, 29.5, 20.8, 20.7, 20.7,
20.6, 20.6, 20.6, 20.5, 20.4; IR (neat) 3385, 2934, 2878, 2100,
1739, 1672, 1602, 1539, 1452, 1371, 1226, 1043, 979, 756,
l
at rt. The solvents were removed in vacuo. The residue was purified
by silica gel column chromatography (hexane/EtOAc = 1:1 to 1:2)
to give 5 (308 mg, 83%). 1H NMR (600 MHz, CDCl3) d 8.95 (1H, s),
8.17 (2H, m), 8.05 (2H, m), 7.61 (4H, m), 7.47 (2H, m), 6.47 (1H,
d, J = 1.8 Hz), 5.45 (1H, t, J = 9.6 Hz), 5.67 (1H, dd, J = 3.6 Hz,
1.8 Hz), 5.29 (1H, dd, J = 10.2 Hz, 3.6 Hz), 5.25 (1H, t, J = 10.2 Hz),
5.20 (1H, dd, J = 3.6 Hz, 1.8 Hz), 5.15 (1H, t, J = 9.6 Hz), 5.11 (1H,
dd, J = 9.6 Hz, 3.6 Hz), 5.07 (1H, d, J = 1.8 Hz), 4.91 (1H, dd,
J = 3.0 Hz, 2.4 Hz), 4.78 (1H, d, 1.8 Hz), 4.53 (1H, dd, J = 9.6 Hz,
3.6 Hz), 4.32 (1H, m), 4.18 (2H, m), 4.07 (2H, m), 3.96 (1H, dd,
J = 12.0 Hz, 1.8 Hz), 3.94 (1H, dd, J = 12.0 Hz, 2.4 Hz), 3.90 (1H, dd,
J = 11.4 Hz, 6.6 Hz), 3.67 (1H, dd, J = 11.4 Hz, 1.8 Hz), 2.11 (3H, s),
2.08 (3H, s), 2.06 (3H, s), 1.98 (3H, s), 1.95 (3H, s), 1.92 (3H, s),
1.89 (3H, s), 1.84 (3H, s); 13C NMR (150 MHz, CDCl3) d 170.6,
170.5, 169.9, 169.7, 169.6, 169.5, 169.2, 169.1, 165.7, 165.2,
159.6, 133.9, 133.7, 130.2, 129.9, 129.0, 128.9, 128.7, 128.6,
128.5, 128.5, 128.2, 99.7, 97.2, 94.3, 75.6, 72.0, 70.3, 69.4, 69.2,
68.9, 68.4, 68.2, 68.0, 67.9, 66.3, 65.9, 65.7, 62.2, 61.9, 53.4, 20.8,
20.7, 20.6, 20.6, 20.6, 20.5; HRMS (ESI) calcd for C50H56O26NCl3
[M+Na]+: 1214.2054, found 1214.2053.
715 cmꢀ1
;
HRMS (ESI) calcd for C61H80O31N4 [M+Na]+:
1387.4704, found 1387.4701.
4.3.6. Protected trimannoside derivative (13)
The mixture of 10 (200 mg, 0.15 mmol) and Pd on C (100 mg) in
THF/EtOH (1:1) was stirred was stirred under hydrogen atmo-
sphere at rt for 60 min. The catalyst was filtered off, and the filtrate
was condensed in vacuo to give 11 as syrup. A mixture of 11
(172 mg) and 1229 (0.04 mmol, 30 mg) in dry THF (4 ml) was stir-
red at rt for 12 h. Then the mixture was concentrated, and the res-
idue was purified by silica gel chromatography to yield 13
4.3.4. 3-Azidopropyl-2,3,4,6-tetra-O-acetyl-
(1 ? 3)-[2,3,4,6-tetra-O-acetyl- -mannopyranosyl-(1 ? 6)]-
2,4-di-O-benzoyl-
a-D-mannopyranosyl-
a-D
a-D-mannopyranoside (7)
A solution of 3-azido-1-propanol 632,33 (173 mg, 1.71 mmol)
and 5 (227 mg, 0.19 mmol) in dry CH2Cl2 (2 ml), containing 4 Å
molecular sieves, was stirred under Ar at 0 °C. Then TMSOTf
(78.2 mg, 52%, two steps yield). ½a D21
ꢁ
+6.61 (c = 1.25 in CHCl3); 1H
NMR (600 MHz, CDCl3) d 8.14 (2H ꢂ 2, m), 8.07 (2H ꢂ 2, m), 7.60
(2H ꢂ 2, m), 7.55 (2H ꢂ 2, m), 7.46 (2H ꢂ 2, m), 7.11 (1H ꢂ 2, br
m), 6.19 (1H ꢂ 2, br m), 5.65 (1H ꢂ 2, t, J = 9.6 Hz), 5.49 (1H ꢂ 2,
dd, J = 3.0 Hz, 1.8 Hz), 5.34 (1H ꢂ 2, dd, J = 10.2 Hz, 3.6 Hz), 5.24
(2H ꢂ 2, m), 5.10 (2H ꢂ 2, m), 5.03 (1H ꢂ 2, d, J = 1.8 Hz), 5.02
(1H ꢂ 2, d, J = 1.8 Hz), 4.87 (1H ꢂ 2, dd, J = 3.0 Hz, 1.8 Hz), 4.80
(1H ꢂ 2, d, J = 1.8 Hz), 4.46 (1H ꢂ 2, dd, J = 9.6 Hz, 3.0 Hz), 4.14
(3H ꢂ 2, m), 4.02 (5H ꢂ 2, m), 3.96 (1H ꢂ 2, dd, J = 12.0 Hz,
2.4 Hz), 3.90 (1H ꢂ 2, dd, J = 10.8 Hz, 6.6 Hz), 3.85 (1H ꢂ 2, m),
3.68 (8H ꢂ 2, m), 3.63 (5H ꢂ 2, m), 3.58 (2H ꢂ 2, m), 3.55
(2H ꢂ 2, m), 3.49 (1H ꢂ 2, m), 3.42 (2H ꢂ 2, m), 2.67 (2H ꢂ 2, t,
J = 7.2 Hz), 2.12 (2H ꢂ 2, t, J = 7.2 Hz), 2.11 (3H ꢂ 2, s), 2.10
(2.8 ll, 0.015 mmol) was added, and the reaction mixture was stir-
red for 1 h. The mixture was neutralized with aqueous NaHCO3.
The organic layer was dried, filtered, and concentrated. The residue
was purified by column chromatography (hexane/EtOAc = 1:1) to
obtain 7 (155 mg, 72%). ½a D26
ꢁ
+12.48 (c = 0.5 in CHCl3); 1H NMR
(600 MHz, CDCl3) d 8.14 (2H, m), 8.04 (2H, m), 7.61 (2H, m), 7.54
(2H, m), 7.47 (2H, m), 5.59 (1H, t, J = 10.2 Hz), 5.50 (1H, dd,
J = 3.6 Hz, 1.8 Hz), 5.34 (1H, dd, J = 10.2 Hz, 3.6 Hz), 5.24 (1H, t,
J = 10.2 Hz), 5.22 (1H, dd, J = 3.6 Hz, 1.8 Hz), 5.11 (2H, m), 5.04
(1H, d, J = 1.8 Hz), 5.02 (1H, d, J = 1.8 Hz), 4.88 (1H, m), 4.80 (1H,
d, J = 1.8 Hz), 4.44 (1H, dd, J = 10.2 Hz, 3.6 Hz), 4.08 (8H, m), 3.95