9240
T. Murakami et al. / Tetrahedron 61 (2005) 9233–9241
by chromatography (eluting with hexane/AcOEt mixture
11:1/9:1) to afford 25 (60 mg, 97%) as a colorless oil.
aqueous layers were extracted with AcOEt (2!20 mL), and
the organic extracts were dried and concentrated. The
residue was purified by preparative TLC with hexane/
AcOEt 5:2 to afford the glycoside 29 (65 mg, 83%) as a
colorless solid. Rf 0.30 (hexane/AcOEt 5:2); [a]2D4C16.8 (c
1.3, CHCl3); 1H NMR (CDCl3) d 0.88 (t, JZ6.6 Hz, 6H, 18-
and 160-CH3), 1.25 (s-like, 38H, 19!CH2), 1.53 (s, 3H,
branched CH3), 1.70 (m, 2H, 30-H2), 1.90 (m, 2H, 10-H2),
1.93 (s, 3H, CH3CO), 2.00 (m, 4H, 6-H2, 7-H2), 3.74 (dd,
JZ4.3, 10.4 Hz, 1H, 1-Ha), 4.11 (m, 1H, 500-H), 4.16 (dd,
JZ3.4, 10.4 Hz, 1H, 1-Hb), 4.33 (dd, JZ4.9, 12.2 Hz, 1H,
600-Hb), 4.48 (dd, JZ3.2, 12.1 Hz, 1H, 600-Ha), 4.50 (m, 1H,
2-H), 4.86 (d, JZ7.8 Hz, 1H, 100-H), 5.00 (dd, JZ5.1,
6.8 Hz, 1H, 20-H), 5.04 (m, 1H, 8-H), 5.50 (dd, JZ7.8,
9.5 Hz, 1H, 200-H), 5.52 (m, 1H, 3-H), 5.63 (t, JZ9.8 Hz,
1H, 40-H), 5.65 (m, 1H, 4-H), 5.85 (m, 1H, 5-H), 5.87 (t, JZ
9.6 Hz, 1H, 300-H), 6.47 (d, JZ9.0 Hz, 1H, NH), 7.22–7.56
(m, 15H), 7.80 (m, 2H), 7.87 (m, 2H), 7.92 (m, 2H), 7.95 (m,
2H), 7.99 (m, 2H); 13C NMR (CDCl3) d 14.1, 15.9, 20.6,
22.7, 24.6, 27.3, 28.0, 29.32, 29.35, 29.40, 29.53, 29.60,
29.63, 29.68, 31.78, 31.88, 31.89, 32.5, 39.6, 50.8, 62.9,
67.5, 69.5, 72.1, 72.4, 72.9, 73.9, 74.0, 100.8, 123.0, 124.7,
128.26, 128.29, 128.33, 128.35, 128.42, 128.8, 129.1, 129.5,
129.6, 129.7, 129.8, 130.1, 132.97, 133.01, 133.2, 133.3,
133.4, 136.1, 137.0, 165.0, 165.10, 165.15, 165.7, 165.9,
169.5, 169.6; FAB-MS (positive, NBA) m/z (%) 1313.3
([MCNa]C, 30), 1168.9 ([MKPhCO2]C, 42), 579.2 (62).
1
[a]2D5K35.3 (c 1.2, CHCl3); H NMR (C6D6, 75 8C) d 0.89
(t, JZ6.7 Hz, 3H), 1.29 (s-like, 14H), 1.47 (s, 12H), 1.53 (s,
3H), 1.59 (s, 3H), 1.97 (m, 2H), 2.03 (m, 4H), 3.78 (dd, JZ
7.3, 8.3 Hz, 1H), 4.08 (m, 1H), 4.15 (d, JZ8.8 Hz, 1H), 5.15
(m, 1H), 5.50 (dd, JZ6.0, 15.3 Hz, 1H), 5.90 (td, JZ6.6,
15.4 Hz, 1H), 6.29 (m, 1H), 7.11 (m, 3H), 8.22 (m, 2H); 13C
NMR (C6D6, 75 8C) d 14.1, 16.1, 23.0, 24.4, 27.0,
27.8, 28.47, 28.50, 29.69, 29.74, 29.9, 30.0, 32.2, 32.9,
40.1, 60.7, 64.0, 73.3, 80.0, 123.7, 126.6, 128.5 (2C),
130.2 (2C), 131.5, 132.7, 135.1, 136.2, 152.3, 165.5;
HRMS (EI) calcd for C34H53NO5 (MC) 555.3924, found
555.3949.
4.5.2. (2S,3R,4E,8E,20R)-3-Benzoyloxy-2-(20-acetoxyhexa-
decanoyl)amino-9-methyl-4,8-octadecadien-1-ol (27). To
a stirred solution of benzoate 25 (40 mg, 0. 072 mmol) in
EtOH (0.8 mL) was added a 2.0 M aq HCl (0.2 mL) and the
mixture was stirred for 4 h at 70 8C. To this solution were
added CHCl3/MeOH 7:1 (10 mL) and H2O (10 mL). The
layers were separated and the aqueous phase was extracted
with CHCl3/MeOH 7:1 (2!10 mL). The combined organic
extracts were dried and concentrated in vacuo to give crude
3-O-benzoyl-sphingadienine hydrochloride 26 (35 mg) as a
colorless solid. This solid (35 mg) and (R)-acetoxypalmitate
24 (38 mg, 0.092 mmol) were dissolved in THF (1 mL). To
this solution was added Et3N (15 mg, 0.15 mmol) in THF
(0.2 mL), and the mixture was stirred at rt for 20 h. The
reaction mixture was diluted with AcOEt and H2O, and
extracted with AcOEt (3!10 mL). The combined organic
layers were dried and concentrated to give a yellow oil,
which was purified by preparative TLC with hexane/AcOEt
3:2 to give 27 (36 mg, 70%) as a colorless solid. Rf 0.27
(hexane/AcOEt 3:2); mp 56–58 8C. [a]2D4C30.6 (c 0.70,
4.5.4. (2S,3R,4E,8E,20R)-1-O-(b-D-Glucopyranosyl)-2-
(20-hydroxyhexadecanoyl)amino-9-methyl-4,8-octadeca-
diene-1,3-diol (1b). To a stirred solution of 29 (55 mg,
45 mmol) in MeOH (0.8 mL) and THF (0.8 mL) was added
1.0 M solution of NaOMe in MeOH (60 mL, 60 mmol), and
the mixture was stirred for 2 h at 5–10 8C. Acetic acid
(10 mg) was added and the solvent was removed. The
residue was purified by silica gel column chromatography
eluting with CH2Cl2/MeOH 9:1/7:1 to afford the cere-
broside 1b (28 mg, 86%) as a colorless amorphous solid. Rf
0.33 (CH2Cl2/MeOH 7:1). [a]2D4C3.5 (c 0.56, CHCl3/
1
CHCl3); H NMR (CDCl3) d 0.88 (t, JZ6.6 Hz, 6H), 1.25
(s-like, 38H), 1.55 (s, 3H), 1.81 (m, 2H), 1.92 (t, JZ7.3 Hz,
2H), 2.08 (m, 4H), 2.15 (s, 3H), 2.82 (br, 1H), 3.69 (dd, JZ
3.2, 12.0 Hz, 1H), 3.76 (dd, JZ3.7, 12.0 Hz, 1H), 4.24 (m,
1H), 5.07 (m, 1H), 5.17 (dd, JZ4.7, 7.2 Hz, 1H), 5.60 (m,
2H), 5.90 (dt, JZ14.4, 6.3 Hz, 1H), 6.80 (d, JZ8.3 Hz, 1H),
7.46 (m, 2H), 7.60 (m, 1H), 8.04 (m, 2H); 13C NMR
(CDCl3) d 14.1, 16.0, 20.9, 22.7, 24.8, 27.2, 28.0, 29.29,
29.35, 29.41, 29.54, 29.62, 29.65, 29.69, 31.9, 32.5, 39.7,
53.5, 61.5, 74.1, 74.4, 122.8, 124.7, 128.5 (2C), 129.5, 129.8
(2C), 133.5, 136.3, 137.0, 166.6, 169.7, 170.2. Anal. Calcd
for C44H73NO6: C, 74.22; H, 10.33; N, 1.97. Found: C,
74.14; H, 10.48; N, 1.94.
1
MeOH 1:1); {lit.3e [a]2D7C5.1 (c 0.3, MeOH)}; H NMR
(pyridine-d5 with 2% D2O) d 0.84 (t, 6H, JZ6.6 Hz, 18- and
160-CH3), 1.23 (s-like, 36H, 18!CH2), 1.35 (m, 2H,
11-H2), 1.59 (s, 3H, 19-CH3), 1.73 (br, 2H, 30-H2), 1.99 (t,
JZ7.3 Hz, 2H, 10-H2), 2.12 (m, 4H, 6-H2, 7-H2), 3.87 (m,
1H, 500-H), 4.00 (dd, JZ7.6, 9.0 Hz, 1H, 200-H), 4.18 (m, 3H,
1-Ha, 300-H, 400-H), 4.31 (dd, JZ5.2, 11.8 Hz, 1H, 600-Ha),
4.48 (dd, JZ2.3, 11.5 Hz, 1H, 600-Hb), 4.55 (dd, JZ3.8,
7.9 Hz, 1H, 20-H), 4.69 (dd, JZ5.4, 10.7 Hz, 1H, 1-Hb),
4.73 (m, 1H, 3-H), 4.78 (m, 1H, 2-H), 4.88 (d, JZ7.6 Hz,
1H, 100-H), 5.22 (m, 1H, 8-H), 5.90 (br d, JZ15.4 Hz, 1H,
5-H), 5.99 (dd, JZ5.1, 15.4 Hz, 1H, 4-H), 8.34 (d, JZ
8.5 Hz, 1H, NH); 13C NMR (pyridine-d5) d 14.2 (C-18 and
160), 16.0 (C-19), 22.9 (C-17 and 150), 25.8 (C-40), 28.1
(C-7), 28.3 (C-11), 29.56, 29.59, 29.82, 29.85, 29.88, 29.95
(C-12–15 and 50-130), 32.1 (C-16 and 140), 33.0 (C-6), 35.6
(C-30), 39.9 (C-10), 54.5 (C-2), 62.5 (C-600), 70.0 (C-1), 71.4
(C-400), 72.2 (C-20), 72.4 (C-3), 75.0 (C-200), 78.3 (C-300),
78.4 (C-500), 105.5 (C-100), 124.1 (C-8), 131.8 (C-4), 132.3
(C-5), 135.8 (C-9), 175.7 (C-10); FAB-MS (positive, NBA)
m/z (%) 750.6 ([MCNa]C, 45), 710.6 ([MKOH]C, 6),
548.6 ([MKOH–Glc]C, 12), 320.3 (5), 276.4 (12).
4.5.3. (2S,3R,4E,8E,20R)-2-(20-Acetoxyhexadecanoyl)
amino-3-O-benzoyl-1-O-(200,300,400,600-tetra-O-benzoyl-b-
D-glucopyranosyl)-9-methyl-4,8-octadecadiene-1,3-diol
(29). A solution of 27 (43 mg, 0.06 mmol), 2,3,4,6-tetra-O-
benzoyl-a-D-glucosyl bromide 28 (68 mg, 0.10 mmol),
˚
oven-dried molecular sieves 4 A (80 mg) in dichloro-
methane (2.5 mL) was stirred under argon at rt for 30 min
before being cooled to K20 8C. To this suspension was
added AgOTf (27 mg, 0.10 mmol) in toluene (0.5 mL), and
the mixture was stirred at K20–0 8C for 2 h. The resulting
suspension was diluted with AcOEt (10 mL), and the
insoluble material was filtered off and washed thoroughly
with AcOEt (15 mL). The filtrate was washed with aq
NaHCO3, H2O, and brine (10 mL each). The combined