D.-S. Wang et al. / Bioorg. Med. Chem. 9 (2001) 133±139
137
2
0
ꢀ
[
1
3
(+)-3aMe]: colorless oil (216 mg, 96%); [a] +2.9 (c
0.87 (t, J=6.9 Hz, 3H), 1.25 (br s, 30H), 1.52±1.61 (m,
2H), 2.16 (br s, 1H), 3.39±3.46 (m, 3H), 3.46 (s, 3H),
3.52 (t, J=4.5 Hz, 2H), 3.65 (dd, J=5.1, 11.4 Hz, 1H),
3.75 (dd, J=4.2, 11.1 Hz, 1H).
D
1
.5, CHCl ); H NMR (CDCl ) d 0.87 (t, J=6.9 Hz,
H), 1.27 (br s, 10H), 1.49±1.60 (m, 2H), 3.41 (t,
J=6.6 Hz, 2H), 3.45 (s, 3H), 3.48±3.58 (m, 5H), 3.80 (s,
H), 4.48 (s, 2H), 6.88 (d, J=8.7 Hz, 2H), 7.26 (d,
3
3
3
J=8.7 Hz, 2H). (+)-1-O-Hexadecyl-2-O-methyl-3-(4-
methoxybenzyl) - sn - glycerol [(+) - 3bMe]: amorphous
General procedure for the preparation of (+)-5aAc, (+)-
5bAc, (+)-5cAc, (+)-5aMe, (+)-5bMe, and (+)-5cMe.
To a solution of the aforementioned alcohol (0.49 mmol)
in anhyd CH Cl (3mL) was added a solution of benzyl-
20
ꢀ
1
solid (273 mg, 91%); [a] +2.4 (c 1.2, CHCl ); H
D
3
NMR (CDCl ) d 0.87 (t, J=6.9 Hz, 3H), 1.25 (br s,
3
2
2
0
0
26H), 1.48±1.58 (m, 2H), 3.41 (t, J=6.6 Hz, 2H), 3.45 (s,
N,N,N ,N -tetraisopropylphosphorodiamidite (197 mg,
0.58 mmol) in CH Cl (1 mL), followed by 1H-tetrazole
3H), 3.48±3.58 (m, 5H), 3.80 (s, 3H), 4.48 (s, 2H), 6.88
2
2
(
Calcd m/z for C H O : 450.371. Found: 473.366
d, J=8.7 Hz, 2H), 7.25 (d, J=8.7 Hz, 2H). HRMS:
(42 mg, 0.58 mmol) under an argon atmosphere. After
3 h, the volatiles were removed in vacuo, and the residue
was puri®ed by column chromatography (silica gel; hex-
ane:triethylamine, 10:1) to produce the phosphoramidite
derivative. (+)-1-O-Octyl-2-O-acetyl-sn-glycerol benzyl-
(N,N - diisopropylamino)phosphoramidite [(+) - 5aAc]:
2
8
50
4
(
M+Na). (+)-1-O-Octadecyl-2-O-methyl-3-(4-methoxy-
benzyl)-sn-glycerol [(+)-3cMe]: amorphous solid
2
0
ꢀ
302 mg, 95%); [a] +2.2 (c 0.8, CHCl ); H NMR
D
1
(
(
3
CDCl ) d 0.87 (t, J=6.9 Hz, 3H), 1.25 (br s, 30H),
3
2
0
ꢀ
colorless oil (187 mg, 96%); [a] +6.2 (c 1.6, CHCl );
D
1
1.47±1.60 (m, 2H), 3.41 (t, J=6.6 Hz, 2H), 3.45 (s, 3H),
3
3.49±3.57 (m, 5H), 3.80 (s, 3H), 4.48 (s, 2H), 6.88 (d,
J=8.7 Hz, 2H), 7.25 (d, J=8.7 Hz, 2H).
H NMR (CDCl ) d 0.87 (t, J=6.9 Hz, 3H), 1.18 (d,
3
J=3 Hz, 6H), 1.20 (d, J=3 Hz, 6H), 1.26 (br s, 10H),
.48±1.58 (m, 2H), 2.06 (s, 3H), 3.35±3.88 (m, 8H),
4.62±4.77 (m, 2H), 4.90±5.16 (m, 1H), 7.24±7.34 (m, 5H);
1
General procedure for the preparation of (� )-4aAc, (� )-
31
4
bAc, (� )-4cAc, (� )-4aMe, (� )-4bMe, and (� )-4cMe.
P NMR (CDCl , H PO as external reference) d 150.90
3
3
4
To a solution of the aforementioned 3-PMB ether
0.57 mmol) in wet CH Cl2 (20 mL), DDQ (270 mg,
and 151.05 (1:1). (+)-1-O-Hexadecyl-2-O-acetyl-sn-gly-
cerol benzyl - (N,N - diisopropylamino)phosphoramidite
(
2
2
0
ꢀ
1.19 mmol) was added in portions. The resulting mix-
ture was stirred at rt for 4 h, diluted with CH Cl2
[(+)-5bAc]: colorless oil (289 mg, 95%); [a] +4.8 (c
D
1
1.5, CHCl ); H NMR (CDCl ) d 0.87 (t, J=6.9 Hz,
2
3
3
(
dried over Na SO , and concd. The residue was puri®ed
20 mL), washed with 10% aq NaHCO , and brine,
3H), 1.18 (d, J=3 Hz, 6H), 1.22 (d, J=3 Hz, 6H), 1.25
(br s, 26H), 1.48±1.58 (m, 2H), 2.05 (s, 3H), 3.34±3.86
(m, 8H), 4.62±4.77 (m, 2H), 5.08±5.16 (m, 1H), 7.20±7.34
(m, 5H); 31P NMR (CDCl , H PO as external reference)
3
2
4
by column chromatography (silica gel; hexane:ether,
:2) to give the 3-hydroxy derivative. (� )-1-O-Octyl-2-
1
3
3
4
O-acetyl-sn-glycerol [(� )-4aAc]: colorless oil (132 mg,
d 150.89 and 151.04 (1:1). (+)-1-O-Octadecyl-2-O-acetyl-
2
0
ꢀ
1
9
0
2
3
3%); [a] � 18.9 (c 0.8, CHCl ); H NMR (CDCl ) d
sn-glycerol
benzyl-(N,N-diisopropylamino)phosphor-
D
3
3
20
.87 (t, J=6.9 Hz, 3H), 1.27 (br s, 10H), 1.50±1.62 (m,
H), 2.10 (s, 3H), 2.31 (br s, 1H), 3.41±3.50 (m, 2H),
.60±3.64 (m, 2H), 3.81 (d, J=4.2 Hz, 2H), 4.95±5.01
amidite [(+)-5cAc]: colorless oil (298 mg, 98%); [a]
D
ꢀ
1
+4.1 (c 2.1, CHCl ); H NMR (CDCl ) d 0.87 (t,
3
3
J=6.9 Hz, 3H), 1.18 (d, J=3 Hz, 6H), 1.20 (d, J=3 Hz,
6H), 1.25 (br s, 30H), 1.48±1.58 (m, 2H), 2.06 (s, 3H),
3.38±3.87 (m, 8H), 4.50±4.60 (m, 2H), 5.08±5.16 (m,
(
m, 1H). (� )-1-O-Hexadecyl-2-O-acetyl-sn-glycerol [(� )-
2
0
ꢀ
4
0
3
2
3
bAc]: amorphous solid (191 mg, 91%); [a] � 11.1 (c
D
1
31
.4, CHCl ); H NMR (CDCl ) d 0.87 (t, J=6.9 Hz,
1H), 7.20±7.40 (m, 5H); P NMR (CDCl , H PO as
3
3
3
3
4
H), 1.25 (br s, 26H), 1.55±1.59 (m, 2H), 2.11 (br s, 3H),
.21 (br s, 1H), 3.42±3.48 (m, 2H), 3.61±3.64 (m, 2H),
.82 (d, J=3.6 Hz, 2H), 4.96±5.02 (m, 1H). (� )-1-O -
external reference) d 150.25 and 151.42 (1:1). (+)-1-O-
Octyl-2-O-methyl-sn-glycerol benzyl-(N,N-diisopropyl-
amino)phosphoramidite [(+)-5aMe]: colorless oil (202
2
0
ꢀ
mg, 91%); [a] +4.5 (c 3, CHCl ); H NMR (CDCl )
D
1
Octadecyl-2-O-acetyl-sn-glycerol [(� )-4cAc]: amorphous
3
3
2
0
ꢀ
1
solid (192 mg, 85%); [a] � 11 (c 1.3, CHCl ); H NMR
d 0.87 (t, J=6.9 Hz, 3H), 1.18 (d, J=3 Hz, 6H), 1.20 (d,
J=3 Hz, 6H), 1.26 (br s, 10H), 1.51±1.61 (m, 2H), 3.40±
D
3
(
CDCl ) d 0.87 (t, J=6.9 Hz, 3H), 1.25 (br s, 30H),
3
3
1
1
3
2
.51±1.61 (m, 2H), 2.11 (br s, 3H), 2.22 (br s, 1H), 3.38±
.51 (m, 2H), 3.57±3.67 (m, 2H), 3.82 (d, J=3.6 Hz,
H), 4.95±5.02 (m, 1H). (� )-1-O-Octyl-2-O-methyl-sn-
3.80 (m, 10H), 4.63±4.79 (m, 2H), 7.22±7.41 (m, 5H);
P
NMR (CDCl , H PO as external reference) d 150.25
3
3
4
and 151.41 (1:1). (+)-1-O-Hexadecyl-2-O-methyl-sn-
glycerol benzyl-(N,N-diisopropylamino)phosphoramidite
2
0
glycerol [(� )-4aMe]: colorless oil (110 mg, 86%); [a]
D
ꢀ
J=6.9 Hz, 3H), 1.26 (br s, 10H), 1.52±1.60 (m, 2H), 2.18
1
20
D
ꢀ
�
7.8 (c 1.8, CHCl ); H NMR (CDCl ) d 0.87 (t,
[(+)-5bMe]: colorless oil (262 mg, 93%); [a] +3.7 (c
3
3
1
1.4, CHCl ); H NMR (CDCl ) d 0.87 (t, J=6.9 Hz,
3
3
(
2
1
br s, 1H), 3.38±3.45 (m, 3H), 3.46 (s, 3H), 3.49±3.58 (m,
3H), 1.19 (d, J=3 Hz, 6H), 1.21 (d, J=3 Hz, 6H), 1.25
(br s, 26H), 1.51±1.60 (m, 2H), 3.40±3.80 (m, 10H),
4.62±4.80 (m, 2H), 7.20±7.38 (m, 5H); 31P NMR (CD
Cl , H PO as external reference) d 150.28 and 151.45
H), 3.65 (dd, J=5.4, 11.4 Hz, 1H), 3.74 (dd, J=4.2,
1.1 Hz, 1H). (� )-1-O-Hexadecyl-2-O-methyl-sn-glycerol
2
0
ꢀ
[
(
(� )-4bMe]: amorphous solid (148 mg, 78%); [a] � 6.0
D
3
3
4
1
c 1.3, CHCl ); H NMR (CDCl ) d 0.87 (t, J=6.9 Hz,
(1:1). (+)-1-O-Octadeyl-2-O-methyl-sn-glycerol benzyl-
3
3
3H), 1.25 (br s, 26 H), 1.51±1.61 (m, 2 H), 2.11 (br s, 1
H), 3.39±3.46 (m, 3 H), 3.46 (s, 3 H), 3.53 (t, J=4.5 Hz,
(N,N - diisopropylamino)phosphoramidite [(+) - 5cMe]:
2
0
ꢀ
colorless oil (281 mg, 97%); [a] +4.2 (c 2.9, CHCl );
D
1
3
2
1
H), 3.67 (dd, J=5.1, 11.4 Hz, 1 H), 3.75 (dd, J=4.2,
1.1 Hz, 1 H). HRMS: Calcd m/z for C H O : 330.313.
H NMR (CDCl ) d 0.87 (t, J=6.9 Hz, 3H), 1.19 (d,
3
J=3 Hz, 6H), 1.21 (d, J=3 Hz, 6H), 1.25 (br s, 30H),
1.52±1.60 (m, 2H), 3.36±3.80 (m, 10H), 4.64±4.79 (m,
2H), 7.20±7.40 (m, 5H); 31P NMR (CDCl , H PO as
20
42 3
Found: 353.307 (M+Na). (� )-1-O-Octadecyl-2-O-
methyl-sn-glycerol [(� )-4cMe]: amorphous solid (160 mg,
3
3
4
2
0
ꢀ
1
7
4%); [a] � 5.7 (c 0.9, CHCl ); H NMR (CDCl ) d
external reference) d 150.28 and 151.45 (1:1).
D
3
3