6808 J . Org. Chem., Vol. 62, No. 20, 1997
Fuji et al.
carbonate, and brine successively, dried, and concentrated to
yield a crystalline residue. Recrystallization from n-hexane-
ethyl acetate afforded 45.30 g (97%) of 7 as colorless plates.
Mp 66-66.5 °C [lit.14a Mp 63-64 °C; lit.14b mp 62.5-63.5 °C].
[R]26 +2.5° (c 3.00, THF) [lit.14a [R]25 +2.69° (c 3.5, THF)].
5.8 Hz, 1H), 3.32 (dd, J ) 9.2, 5.4 Hz, 1H), 3.40 (t, J ) 6.6 Hz,
2H), 3.55-3.70 (m, 2H), 7.15-7.50 (m, 15H). 13C NMR (CDCl3)
δ 14.12, 22.70, 26.16, 29.38, 29.54, 29.62, 29.65, 29.68, 29.72,
31.95, 39.88, 64.86, 71.34, 72.57, 86.63, 127.07, 127.84, 128.77,
144.06. LSIMS m/ z 597 (M + Na)+. Anal. Calcd for
C38H54O2S: C, 79.39; H, 9.47; S, 5.58. Found: C, 79.28; H,
9.46; S, 5.55.
D
D
IR (KBr): 3415, 3335, 3250, 1460, 1130, 1050 cm-1. H NMR
(CDCl3) δ 0.88 (t, J ) 6.4 Hz, 3H), 1.10-1.45 (m, 26H), 1.45-
1.65 (m, 2H), 2.20 (dd, J ) 6.4, 5.4 Hz, OH), 2.63 (d, J ) 5.0
Hz, OH), 3.40-3.93 (m, 7H). Anal. Calcd for C19H40O3: C,
72.10; H, 12.74. Found: C, 71.95; H, 12.68.
1
Attem p t to Con ver t Com p ou n d 10 to In ter m ed ia te B
(S-ben zyl). To a solution of 491 mg (0.854 mmol) of 10 in 10
mL of N,N-dimethylformamide were added dropwise 0.11 mL
(0.897 mmol) of benzyl bromide and 0.94 mL (0.940 mmol) of
1 N sodium methoxide at room temperature, and the mixture
was stirred for 15 min. The reaction mixture was partitioned
between ethyl acetate and 1 N hydrochloric acid, and the
organic solution was washed with water and brine succes-
sively, dried, and concentrated. The residual oil (560 mg) was
dissolved in 10 mL of dichloromethane. To this was added
0.87 mL of 12 wt % boron trifluoride-methanol complex in
methanol at room temperature, and the mixture was stirred
for 1 h. The reaction mixture was poured into ice-cold water
and extracted with chloroform. The organic solution was
washed with water and brine successively, dried, and concen-
trated to yield 342 mg (95%) of 11a as a colorless oil. 1H NMR
(CDCl3) δ 0.88 (t, J ) 6.4 Hz, 3H), 1.10-1.40 (m, 26H), 1.40-
1.65 (m, 2H), 2.60 (t, J ) 6.2 Hz, 1H), 2.85-3.00 (m, 1H), 3.33-
3.44 (m, 2H), 3.48 (dd, J ) 9.6, 9.6 Hz, 1H), 3.59 (dd, J ) 9.6,
4.8 Hz, 1H), 3.64-3.82 (m, 2H), 3.78 (s, 2H), 7.20-7.30 (m,
5H).
3-O-Hexa d ecyl-1-O-tr ityl-sn -glycer ol (8). A mixture of
42.98 g (0.136 mol) of 7, 45.43 g (0.163 mol) of triphenylmethyl
chloride, and 37.9 mL (0.163 mol) of triethylamine in 470 mL
of tetrahydrofuran and 120 mL of acetonitrile was refluxed
for 15 h. The reaction mixture was concentrated and filtered
to remove the precipitated triethylamine hydrochloride. The
salt was washed thoroughly with ethyl acetate. The filtrate
and washings were combined and washed with water, 0.1 N
hydrochloric acid, saturated sodium hydrogencarbonate, and
brine successively. The solution was dried and concentrated
to yield 85.36 g of crude compound 8 as pale-yellowish crystals,
which were used for the next step without further purification.
A small amount of crude 8 was purified by silica gel chroma-
tography, eluting with n-hexane-EtOAc (9:1), to yield pure
615 as colorless solids. Mp 54-55 °C. [R]24 -2.3° (c 1.00,
D
CHCl3) [lit.15 [R]26 -2.25° (c 1.02, CHCl3)]. IR (KBr): 2915,
D
2850, 1446, 1090 cm-1
.
1H NMR (CDCl3) δ 0.88 (t, J ) 6.8
Hz, 3H), 1.10-1.40 (m, 26H), 1.40-1.65 (m, 2H), 2.43 (d, J )
4.8 Hz, 1H), 3.10-3.25 (m, 2H), 3.35-3.60 (m, 4H), 3.88-4.03
(m, 1H), 7.17-7.55 (m, 15H). Anal. Calcd for C38H54O3: C,
81.67; H, 9.74. Found: C, 81.66; H, 9.74.
To a solution of 338 mg (0.800 mmol) of 11a and 0.16 mL
(1.14 mmol) of triethylamine in 3 mL of chloroform was added
dropwise a solution of 216 mg (0.893 mmol) of (2-bromoeth-
yl)phosphodichloridate in 1.5 mL of chloroform at 0 °C. After
stirring for 2 h at room temperature, 4 mL of ether was added
and the mixture was refluxed for 2 h. The reaction mixture
was poured into water and extracted with ether. The organic
solution was washed successively with water and brine, dried,
and concentrated. The residue was purified by silica gel
chromatography, eluting with n-hexane-ethyl acetate (98:2),
to yield 300 mg (85%) of 12 as a colorless oil. This compound
was found to decompose on TLC and during silica gel chro-
matographic separation. IR (film): 1470, 1455, 1118 cm-1. 1H
NMR (CDCl3) δ 0.88 (t, J ) 6.2 Hz, 3H), 1.10-1.45 (m, 26H),
1.45-1.65 (m, 2H), 2.76 (dd, J ) 14.0, 6.2 Hz, 1H), 2.93 (dd, J
) 14.0, 7.0 Hz, 1H), 3.44 (t, J ) 6.6 Hz, 2H), 3.58-3.73 (m,
2H), 3.78 (s, 3H), 3.90-4.08 (m, 1H), 7.20-7.40 (m, 5H).
LSIMS m/ z 463 (M + Na)+. Anal. Calcd for C38H54O2S: C,
70.79; H, 10.28; S, 7.27. Found: C, 71.11; H, 10.26; S, 7.48.
1-O-Hexa d ecyl-2-S-t r it yl-sn -2-t h ioglycer ol (13). To a
solution of 60.68 g (0.106 mol) of 10 in 1.2 L of dichloromethane
was added dropwise 14.3 mL (0.116 mol) of boron trifluoride-
diethyl ether complex at -10 °C. After stirring for 45 min at
the same temperature, the reaction mixture was poured into
ice-cold saturated sodium hydrogencarbonate and extracted
with dichloromethane. The organic solution was washed with
brine, dried, and concentrated. The residue was purified by
silica gel chromatography, eluting with n-hexane-toluene (1:
1) and then ethyl acetate, to yield 51.86 g (85%) of 13 as a
colorless oil. [R]23D -25.8° (c 2.28, CHCl3). IR (CHCl3): 3574,
2-S-Acet yl-1-O-h exa d ecyl-3-O-t r it yl-sn -2-t h ioglycer ol
(9). To a solution of 85.34 g of crude 8 in 880 mL of
dichloromethane were added dropwise 31.9 mL (0.229 mol) of
triethylamine and 11.8 mL (0.152 mol) of methanesulfonyl
chloride at -5 °C. After stirring for another 1.5 h at the same
temperature, the reaction mixture was poured into ice-cold
water. The organic phase was separated, and the aqueous
phase was extracted with dichloromethane. The organic
phases were combined and washed with 0.1 N hydrochloric
acid, saturated sodium hydrogencarbonate, and brine succes-
sively. The solution was dried and concentrated to yield 94.07
g of the mesylate16 as a pale-yellowish oil.
To a solution of 94.07 g of the above mesylate in 800 mL of
N,N-dimethylformamide was added 33.74 g (0.295 mol) of
potassium thioacetate, and the mixture was stirred for 16 h
while heating at 90 °C (bath temperature). An additional
16.87 g (0.148 mol) of potassium thioacetate was added, and
the reaction mixture was stirred for 4 h under the same
conditions. After cooling, the mixture was poured into ice-
cold water and extracted with ethyl acetate. The organic
solution was washed successively with water and brine, dried,
and concentrated. The residue was purified by silica gel
chromatography, eluting with n-hexane-toluene (from 5:1 to
1:2), to yield 68.75 g (82% from 7) of 9 as a reddish-brown oil.
EI-MS m/ z 617 (M + H)+. IR (CHCl3): 1686, 1490, 1466,
1448, 1133, 1114 cm-1
.
1H NMR (CDCl3) δ 0.88 (t, J ) 6.4
Hz, 3H), 1.10-1.40 (m, 26H), 1.40-1.60 (m, 2H), 2.31 (s, 3H),
3.22 (dd, J ) 9.2, 5.6 Hz, 1H), 3.37 (t, J ) 6.6 Hz, 2H), 3.39
(dd, J ) 9.2, 3.8 Hz, 1H), 3.65 (d, J ) 6.0 Hz, 2H), 3.80-3.97
(m, 1H), 7.15-7.50 (m, 15H).
3468, 1595, 1488, 1465, 1444, 1133, 1110 cm-1
.
1H NMR
(CDCl3) δ 0.88 (t, J ) 6.4 Hz, 3H), 1.10-1.35 (m, 26H), 1.35-
1.55 (m, 2H), 2.54-2.72 (m, 2H), 3.00-3.58 (m, 6H), 7.15-
7.35 (m, 9H), 7.40-7.50 (m, 6H). 13C NMR (75 MHz, CDCl3)
δ 14.13, 22.71, 26.05, 29.39, 29.44, 29.52, 29.59, 29.64, 29.69,
29.72, 31.95, 45.42, 64.92, 67.46, 71.47, 72.94, 126.80, 128.00,
129.58, 144.88. LSIMS m/ z 597 (M + Na)+. Anal. Calcd for
C38H54O2S: C, 79.39; H, 9.47; S, 5.58. Found: C, 79.23; H,
9.51; S, 5.52.
1-O-H exa d ecyl-2-S-t r it yl-sn -2-t h ioglycer o-3-O-p h os-
p h och olin e (15). To a solution of 39.83 g (69.3 mmol) of 13
and 22.0 mL (157.8 mmol) of triethylamine in 950 mL of
benzene was added a solution of 18.74 g (131.5 mmol) of
2-chloro-2-oxo-1,3,2-dioxaphospholane in 100 mL of benzene
at room temperature. After stirring for 3.5 h at room tem-
perature, the reaction mixture was filtered to remove the
precipitated salts. The salts were washed with a small amount
of benzene. The filtrate and washings were combined and
1-O-Hexa d ecyl-3-O-tr ityl-sn -2-th ioglycer ol (10). To a
solution of 68.75 g (0.111 mol) of 9 in 400 mL of MeOH and
200 mL of tetrahydrofuran was added dropwise 23.6 mL (0.123
mol) of 28 wt % sodium methoxide solution in methanol at 0
°C. The reaction mixture was stirred for 30 min at the same
temperature and concentrated. The residue was diluted with
ethyl acetate. The solution was washed with 0.1 N hydro-
chloric acid, saturated sodium hydrogencarbonate, and brine
successively, dried and concentrated. The residue was purified
by silica gel chromatography, eluting with n-hexane-toluene
(3:1), to yield 60.68 g (95%) of 10 as colorless solids. Mp 61.5-
63 °C. [R]25 +3.5° (c 1.01, CHCl3). IR (KBr): 3430, 1490,
D
1468, 1450, 1443, 1118, 1093 cm-1
.
1H NMR (CDCl3) δ 0.88
(t, J ) 6.4 Hz, 3H), 1.10-1.40 (m, 26H), 1.40-1.65 (m, 2H),
1.89 (d, J ) 8.2 Hz, SH), 2.95-3.15 (m, 1H), 3.26 (dd, J ) 9.2,