6368
T. Tashiro et al. / Bioorg. Med. Chem. 17 (2009) 6360–6373
(400 MHz, CDCl3): 7.39–7.22 (25H, m), 4.95 (1H, d, J = 11 Hz), 4.84
(1H, d, J = 12 Hz), 4.75 (2H, s), 4.69 (1H, d, J = 12 Hz), 4.47 (1H, d,
J = 11 Hz), 4.42 (2H, s), 4.09 (1H, br s), 3.94–3.89 (2H, m), 3.84
(1H, d, J = 13 Hz), 3.78–3.74 (2H, m), 3.72 (1H, d, J = 13 Hz), 3.68–
3.61 (2H, m), 3.46 (1H, t, J = 8.8 Hz), 3.38 (1H, t, J = 8.0 Hz), 3.26
(1H, dd, J = 8.8, 5.6 Hz), 2.80 (1H, br d, J = 8.0 Hz), 2.12–2.02 (1H,
m), 1.79–1.69 (1H, m), 1.57–1.20 (27H, m), 0.88 (3H, t, J = 7.2 Hz)
ppm; dC (100 MHz, CDCl3): 139.4, 139.1, 138.7, 138.2, 137.9,
128.5, 128.4, 128.3, 128.24, 128.21, 128.1, 127.8, 127.7, 127.6,
127.43, 127.35, 127.30, 81.7, 79.5, 76.8, 75.7, 75.4, 74.6, 73.8,
73.2, 73.0, 71.2, 70.6, 67.1, 62.1, 51.0, 35.8, 34.7, 31.9, 30.0, 29.8,
29.74, 29.71, 29.6, 29.3, 27.2, 25.2, 22.7, 14.1 ppm; HR-FABMS:
calcd for C60H82NO7 [M+H]+ 928.6091; found 928.6085.
3.74 (2H, m), 3.73 (1H, d, J = 13 Hz), 3.70–3.67 (1H, m), 3.66–
3.61 (1H, m), 3.39 (1H, t, J = 8.5 Hz), 3.35 (1H, t, J = 8.5 Hz), 3.27
(3H, s), 3.17 (1H, dd, J = 8.5, 6.0 Hz), 2.81 (1H, br d, J = 8.5 Hz),
2.07–2.00 (1H, m), 1.79–1.70 (1H, m), 1.57–1.22 (30H, m), 0.88
(3H, t, J = 7.0 Hz) ppm; dC (126 MHz, CDCl3): 139.4, 139.1,
138.7, 138.0, 128.5, 128.4, 128.3, 128.2, 128.1, 127.8, 127.7,
127.44, 127.36, 127.32, 127.27, 81.7, 79.5, 76.8, 75.6, 75.4, 74.6,
73.8, 73.0, 72.9, 71.3, 67.2, 62.0, 58.6, 51.0, 35.7, 34.6, 31.9,
30.0, 29.8, 29.72, 29.69, 29.68, 29.63, 29.3, 27.1, 25.2, 22.7,
14.1 ppm; HR-ESIMS: calcd for C54H78NO7 [M+H]+ 852.5773;
found 852.5768.
4.1.3.8. (20S,30S,40R)-1 -(1,2,3/4,5)-2,3,4-Tri-O-benzyl-5-O-(20-N-
D
benzylamino-30,40-dihydroxyoctadecyl)-1-O-methylcyclohexane-
pentol (39e). In the same manner as described above, 38e was
4.1.3.5. (2S,3S,4R)-1-O-(2,3,4-Tri-O-benzyl-5a-carba-a-D-fuco-
pyranosyl)-2-N-benzylaminooctadecane-1,3,4-triol (39b). In the
converted to 39e (85%) as a colorless oil, n2D3 1.5175; ½a D23
ꢂ
+43.0
same manner as described above, 38b was converted to 39b (74%)
(c 1.35, CHCl3); mmax (film): 3460 (br s, OH), 3320 (w, NH), 1605
(w), 1585 (w), 1495 (m), 1095 (br s, C–O), 735 (br s), 700 (s) cm
ꢁ1; dH (500 MHz, CDCl3): 7.39–7.21 (20H, m), 4.852 (1H, d,
J = 12 Hz), 4.847 (1H, d, J = 12 Hz), 4.78 (1H, d, J = 12 Hz), 4.72
(1H, d, J = 12 Hz), 4.68 (1H, d, J = 12 Hz), 4.66 (1H, d, J = 12 Hz),
4.11 (1H, br s), 3.98–3.93 (2H, m), 3.85 (1H, d, J = 13 Hz), 3.77
(1H, dd, J = 9.5, 2.5 Hz), 3.73 (1H, d, J = 13 Hz), 3.69–3.61 (3H, m),
3.38–3.32 (2H, m), 3.26 (3H, s), 2.81 (1H, br d, J = 8.5 Hz), 1.96–
1.84 (2H, m), 1.79–1.73 (1H, m), 1.57–1.48 (1H, m), 1.41–1.20
(27H, m), 0.88 (3H, t, J = 7.0 Hz) ppm; dC (126 MHz, CDCl3):
139.2, 139.1, 138.5, 137.8, 128.6, 128.43, 128.38, 128.3, 128.2,
128.1, 127.9, 127.63, 127.56, 127.43, 127.37, 127.3, 79.6, 79.1,
76.5, 75.5, 75.4, 74.9, 74.01, 73.96, 72.9, 71.2, 67.4, 62.1, 56.5,
51.1, 34.6, 31.9, 30.0, 29.9, 29.8, 29.72, 29.70, 29.69, 29.6, 29.3,
25.3, 22.7, 14.1 ppm; HR-FABMS: calcd for C53H76NO7 [M+H]+:
838.5622; found 838.5620.
as a colorless oil, n2D3 1.5177; ½a D23
ꢂ
+46.6 (c 2.42, CHCl3); mmax (film):
3450 (br s, OH), 3320 (w, NH), 1605 (w), 1585 (w), 1495 (m), 1090
(br s, C–O), 735 (br s), 700 (s) cmꢁ1; dH (500 MHz, CDCl3): 7.39–
7.21 (20H, m), 4.98 (1H, d, J = 11 Hz), 4.84 (1H, d, J = 12 Hz), 4.77
(1H, d, J = 12 Hz), 4.73 (1H, d, J = 12 Hz), 4.69 (1H, d, J = 12 Hz),
4.55 (1H, d, J = 11 Hz), 3.93–3.89 (2H, m), 3.84 (1H, d, J = 13 Hz),
3.76 (2H, dd, J = 9.5, 2.5 Hz), 3.73 (1H, d, J = 13 Hz), 3.70 (1H, br
s), 3.66–3.62 (2H, m), 3.40 (1H, t, J = 8.0 Hz), 2.81 (1H, dt, J = 8.0,
2.5 Hz), 1.88–1.81 (1H, m), 1.80–1.73 (1H, m), 1.56–1.46 (3H, m),
1.42–1.20 (26H, m), 0.94 (3H, d, J = 7.0 Hz), 0.88 (3H, t, J = 7.0 Hz)
ppm; dC (126 MHz, CDCl3): 139.4, 139.2, 138.9, 138.0, 128.5,
128.4, 128.3, 128.20, 128.19, 128.1, 127.8, 127.6, 127.42, 127.37,
127.28, 127.27, 82.0, 80.3, 79.4, 77.1, 75.4, 74.7, 73.7, 73.1, 71.5,
67.2, 62.0, 51.1, 34.6, 32.1, 31.9, 30.2, 30.0, 29.8, 29.72, 29.69,
29.68, 29.67, 29.6, 29.3, 25.3, 22.7, 17.5, 14.1 ppm; HR-FABMS:
calcd for C53H76NO6 [M+H]+: 822.5673; found 822.5674.
4.1.4. Debenzylation and acylation
4.1.3.6. (20S,30S,40R)-1
D
-(1,2,3/4,5)-1,2,3,4-Terta-O-benzyl-5-O-
4.1.4.1. RCAI-37: (20S,30S,40R)-2-O-(20-Hexacosanoylamino-30,40-
dihydroxyoctadecyl)-myo-inositol (1). To a stirred solution of
12 (253 mg, 0.337 mmol) in MeOH (15 mL) and cyclohexene
(20-N-benzylamino-30,40-dihydroxyoctadecyl)cyclohexanepentol
(39c). In the same manner as described above, 38c was converted
to 39c (88%) as a white solid, mp 52.5–54.0 °C; ½a D26
ꢂ
+25.8 (c 1.10,
(3 mL), a 1 M aqueous HCl solution (337 lL, 0.337 mmol) and
CHCl3);
mmax (KBr): 3460 (s, OH), 3380 (m, NH), 1605 (w), 1585 (w),
Pd–C (Kawaken Fine Chemicals Co. Ltd, 10%, dry, 72 mg) were
added at room temperature. After stirring under reflux for 8 h,
the mixture was cooled to room temperature. It was then diluted
with CHCl3/MeOH (5:1) and filtered through a bed of Celite. The
filtrate was concentrated in vacuo to give crude 13 (ca. 190 mg)
as a colorless solid.
1495 (m), 1095 (br s, C–O), 1070 (s, C–O), 1045 (s), 740 (br s), 695
(s) cmꢁ1; dH (400 MHz, CDCl3): 7.40–7.24 (25H, m), 4.86 (1H, br d,
J = 12 Hz), 4.85 (1H, d, J = 12 Hz), 4.80 (1H, d, J = 12 Hz), 4.70 (1H, d,
J = 12 Hz), 4.68 (1H, d, J = 12 Hz), 4.64 (1H, d, J = 12 Hz), 4.47 (1H, d,
J = 12 Hz), 4.42 (1H, d, J = 12 Hz), 4.11 (1H, br s), 3.95 (1H, dd, J = 10,
3.2 Hz), 3.91 (1H, br d, J = 7.6 Hz), 3.81 (1H, d, J = 12 Hz), 3.74 (1H,
dd, J = 10, 2.4 Hz), 3.69 (1H, d, J = 12 Hz), 3.68–3.54 (4H, m), 3.31
(1H, t, J = 8.4 Hz), 2.78 (1H, br d, J =7.6 Hz), 1.98–1.92 (2H, m),
1.78–1.70 (1H, m), 1.57–1.48 (1H, m), 1.38–1.21 (27H, m), 0.88
(3H, t, J = 7.2 Hz) ppm; dC (126 MHz, CDCl3): 139.3, 138.9, 138.6,
138.3, 137.9, 128.6, 128.5, 128.42, 128.40, 128.33, 128.32, 128.1,
128.0, 127.71, 127.66, 127.6, 127.53, 127.49, 127.4, 127.3, 79.6,
79.2, 75.9, 75.8, 75.3, 74.6, 74.10, 74.06, 72.9, 71.3, 70.9, 67.5,
61.8, 51.0, 34.6, 31.9, 30.1, 30.0, 29.82, 29.77, 29.74, 29.73, 29.69,
29.4, 25.3, 22.7, 14.1 ppm; HR-FABMS: calcd for C59H80NO7
[M+H]+ 914.5935; found 914.5932.
To a stirred solution of crude 13 in CHCl3/MeOH (5:1, 30 mL),
Et3N (140 lL, 1.01 mmol) and a solution of cerotyl chloride (14,
freshly prepared, 155 mg, 0.373 mmol) in THF (5 mL) were succes-
sively added at 0 °C. The resulting mixture was stirred at room
temperature overnight, and then concentrated in vacuo. The resid-
ual solid was washed with water and MeOH/H2O (1:2) solution for
removing the ammonium salt, and then dried in the air. The solid
was purified by column chromatography on silica gel (15 g, CHCl3/
MeOH = 50:7) to give 1 (112 mg, 39%, two steps) as colorless pow-
der, mp 195.0–199.0 °C; ½a D22
ꢂ
+1.95 (c 0.30, pyridine); mmax (KBr):
3360 (br s, OH, NH), 1640 (br s, CO), 1540 (br s), 1045 (br s, C–
O), 720 (br m) cmꢁ1; dH (500 MHz, pyridine-d5): 8.68 (1H, d,
J = 8.0 Hz), 7.02 (5H, br s), 6.44 (1H, br s), 5.69 (1H, br s), 5.05–
4.98 (1H, m), 4.95 (1H, dd, J = 11, 4.0 Hz), 4.70 (1H, dd, J = 11,
4.0 Hz), 4.51 (2H, t, J = 9.5 Hz), 4.46 (1H, br s), 4.39 (1H, t,
J = 6.0 Hz), 4.26 (1H, br t, J = 6.0 Hz), 4.11–4.06 (2H, m), 3.96 (1H,
t, J = 9.5 Hz), 2.37 (2H, t, J = 7.0 Hz), 2.26–2.18 (1H, m), 1.97–1.85
(2H, m), 1.83–1.71 (2H, m), 1.71–1.59 (1H, m), 1.46–1.18 (66H,
m), 0.85 (3H, t, J = 7.0 Hz), 0.84 (3H, t, J = 7.0 Hz) ppm; dC
(126 MHz, pyridine-d5): 173.1, 85.8, 77.0, 75.8, 75.3, 75.0, 74.9,
73.81, 73.80, 72.7, 52.6, 36.8, 33.4, 32.11, 32.10, 30.4, 30.2, 30.1,
30.03, 30.02, 30.01, 29.99, 29.98, 29.96, 29.93, 29.90, 29.8, 29.7,
4.1.3.7. (2S,3S,4R)-1-O-(2,3,4-Tri-O-benzyl-6-O-methyl-5a-carba-
a-D-galactopyranosyl)-2-N-benzylaminooctadecane-1,3,4-triol
(39d). In the same manner as described above, 38d was con-
verted to 39d (86%) as colorless oil, n2D4 1.5172; ½a D25
ꢂ
+46.1 (c
1.86, CHCl3); mmax (film): 3460 (br s, OH), 3320 (w, NH), 1605
(w), 1585 (w), 1495 (m), 1090 (br s, C–O), 735 (br s), 700 (s)
cmꢁ1; dH (500 MHz, CDCl3): 7.41–7.20 (20H, m), 4.97 (1H, d,
J = 11 Hz), 4.85 (1H, d, J = 12 Hz), 4.76 (1H, d, J = 12 Hz), 4.74
(1H, d, J = 12 Hz), 4.70 (1H, d, J = 12 Hz), 4.54 (1H, d, J = 11 Hz),
4.07 (1H, br s), 3.95–3.91 (2H, m), 3.85 (1H, d, J = 13 Hz), 3.79–