were measured using a Perkin Elmer 241 polarimeter, in a cell
of 1 dm path length. The concentration (c) is expressed in g 100
cmϪ3 (equivalent to g 0.1 dmϪ3) and values are given in 10Ϫ1 deg
cm2 gϪ1.
OCOCH2CH2), 1.25 (16 H, br s, C11H22NH); δC (100 MHz;
CDCl3) 173.9 (OCO), 159.4 (NHCO), 156.4 (CH3OC), 136.7,
129.8, 129.4, 129.2, 128.4, 128.1, 113.9 (7 × C6H5 and C6H4),
73.1 (CH), 70.6, 68.9, 66.5, 65.4 (4 × CH2), 55.2 (OCH3), 41.1
(CH2NH), 34.1, 29.9, 29.5, 29.4, 29.3, 29.2, 29.1, 29.0, 26.7,
24.5 (10 × CH2); m/z (CI, NH3) [Found (M ϩ H)ϩ 544.3302.
C31H46O7N requires M, 544.3274].
(؉)-1,2-O-Isopropylidene-3-O-(4-methoxybenzyl)-sn-glycerol 6
Sodium hydride (0.48 g, 60% dispersion in mineral oil, 12.00
mmol) was suspended in a solution of dry DMF (5 cm3)
and cooled to 0 ЊC. (S)-(Ϫ)-2,2-Dimethyl-1,3-dioxolane-4-
methanol 5 (1.00 g, 7.56 mmol) was added dropwise and the
solution was warmed to rt and stirred for 1 h. The reaction
mixture was cooled to 0 ЊC and PMBCl (1.77 g, 1.53 cm3, 11.00
mmol) was added dropwise. The reaction mixture was stirred at
rt overnight. The reaction was quenched by careful addition
of water (15 cm3) and the aqueous phase was extracted with
diethyl ether (3 × 15 cm3). The combined ethereal layers were
washed with water (5 × 10 cm3), brine (10 cm3), dried over
MgSO4 and solvent removed in vacuo. Flash chromatography
(20–40% ethyl acetate in hexane) gave the PMB ether (ϩ)-6
(1.71 g, 90%) as a colourless oil: [α]2D0 = ϩ23.7 (c 1.45 in CHCl3)
[lit.,21 [α]2D1 = ϩ21.8 (c 1 in CHCl3)]; δH (250 MHz; CDCl3) 7.27–
7.24 (2 H, m, C6H4OMe), 6.89–6.85 (2 H, m, C6H4OMe), 4.53
(1 H, dd, JAB 11.7, CHAHB), 4.47 (1 H, dd, JAB 11.7, CHAHB),
4.28 (1 H, qn, J 6.3, CH2CHCH2), 4.04 (1 H, dd, J 8.2, 6.3,
CH2CHCH2), 3.79 (3 H, s, OCH3), 3.72 (1 H, dd, J 8.2, 6.3,
CH2CHCH2), 3.53 (1 H, dd, J 9.7, 6.3, CH2CHCH2), 3.43 (1 H,
dd, J 9.7, 6.3, CH2CHCH2), 1.41 (3 H, s, CH3), 1.36 (3 H, s,
CH3).
(؉)-1-O-[12-N-(Benzyloxycarbonyl)aminododecanoyl]-2-O-
hexadecanoyl-3-O-(4-methoxybenzyl)-sn-glycerol 9a
To a solution of alcohol (ϩ)-8 (3.14 g, 5.7 mmol) in dry dichloro-
methane (20 cm3) under nitrogen was added DMAP (0.035 g,
0.29 mmol). The resulting solution was cooled to 0 ЊC and dry
pyridine (0.68 g, 0.70 mL, 8.68 mmol) was added dropwise.
After stirring for 30 min, palmitoyl chloride (1.75 g, 1.93 cm3,
6.37 mmol) was added dropwise under nitrogen and the reac-
tion mixture was stirred overnight at rt. Water (50 cm3) was
added to quench the reaction. The aqueous phase was extracted
with diethyl ether (3 × 50 cm3) and the ethereal layers were
washed with 2 M hydrochloric acid (20 cm3). The acid phase
was back-extracted with diethyl ether (50 cm3) and the com-
bined ethereal layers were washed with brine (20 cm3), dried
over MgSO4 and the solvent was removed in vacuo. Flash
chromatography eluting with 50% ethyl acetate in hexane gave
the ester (ϩ)-9a (3.17 g, 70%) as a white solid (Found: C, 72.6;
H, 9.85; N, 1.8. C47H75O8N requires C, 72.2; H, 9.7; N, 1.8%);
mp 44–47 ЊC (from ethyl acetate); [α]2D0 = ϩ5.5 (c 0.59 in CHCl3);
Rf = 0.20 (20% ethyl acetate in hexane); νmax (CHCl3)/cmϪ1 3451,
2926, 2854, 1728, 1612, 1514, 1405, 1366, 1302, 1252, 1175
and 1110; δH (400 MHz; CDCl3) 7.35–7.30 (5 H, m, C6H5),
7.24–7.22 (2 H, m, C6H4OMe), 6.88–6.86 (2 H, m, C6H4OMe),
5.23–5.21 (1 H, m, CH2CHCH2), 5.09 (2 H, s, OCH2), 4.74 (1
H, br s, NH ), 4.48 (1 H, dd, JAB 12.0, OCHAHB), 4.44 (1 H, dd,
JAB 12.0, OCHAHB), 4.32 (1 H, dd, J 11.8, 3.8, CH2CHCH2),
4.17 (1 H, dd, J 11.8, 6.4, CH2CHCH2), 3.80 (3 H, s, OCH3),
3.55 (2 H, dd, J 5.1, 1.1, CH2CHCH2), 3.18 (2 H, q, J 6.6,
CH2NH), 2.33–2.25 (4 H, m, 2 × OCOCH2), 1.66–1.56 (6 H, m,
2 × OCOCH2CH2, CH2CH2NH), 1.55–1.47 (2 H, m, CH2CH2-
CH2NH), 1.25 (36 H, br s, COC15H31, C11H22NH), 0.88 (3 H, t,
J 6.6, CH3); δC (100 MHz; CDCl3) 173.4, 173.1 (2 × OCO),
159.3 (NHCO), 136.7, 129.8, 129.3, 129.0, 128.5, 128.06, 113.81
(7 × C6H5 and C6H4), 72.9 (CH2), 70.1 (CH), 70.0, 67.9, 66.5,
62.7 (4 × CH2), 55.8 (OCH3), 41.1 (CH2NH), 34.3, 34.1, 31.9,
29.9, 29.7, 29.5, 29.4, 29.3, 29.2, 29.1, 24.9, 24.8, 22.6 (13 ×
CH2), 14.1 (CH3); m/z (CI, NH3) [Found (M ϩ H)ϩ 782.56140.
C47H76O8N requires M, 782.55707].
(R)-3-(4-Methoxybenzyloxy)propane-1,2-diol 7
The PMB ether (ϩ)-6 (7.07 g, 28.0 mmol) was hydrolysed with
TsOH (0.28 g, 1.47 mmol) in methanol (10 cm3) to give the diol
(Ϫ)-7. Flash chromatography eluting with ethyl acetate gave the
diol (Ϫ)-7 (0.23 g, 73%) as a pale yellow solid: mp 41–43 ЊC
(from ethyl acetate) [lit.,22 43.5–45.1 ЊC (from toluene–light
petroleum)]; [α]2D2 = Ϫ1.12 (c 3.04 in CHCl3) [lit.,22 [α]D = Ϫ1.54
(c 3.7 in CHCl3)]; δH (250 MHz; CDCl3) 7.24–7.21 (2 H, m,
C6H4OCH3), 6.87–6.84 (2 H, m, C6H4OCH3), 4.44 (2 H, s,
OCH2), 3.85–3.80 (1 H, m, CH2CHCH2), 3.78 (3 H, s, OCH3),
3.68–3.42 (3 H, m, CH2CHCH2), 3.53 (1 H, dd, J 9.7, 6.3,
CH2CHCH2), 3.31 (1 H, d, J 4.5, OH ), 2.96 (1 H, t, J 5.5, OH ).
(؉)-1-O-[12-N-(Benzyloxycarbonyl)aminododecanoyl]-3-O-
(4-methoxybenzyl)-sn-glycerol 8
The diol (Ϫ)-7 (2.47 g, 12 mmol), DCC (2.64 g, 13 mmol) and
DMAP (1.56 g, 13 mmol) were added to dry dichloromethane
(100 cm3) under nitrogen and the reaction was stirred for 30 min
(؉)-1-O-[12-N-(Benzyloxycarbonyl)aminododecanoyl]-2-O-
dodecanoyl-3-O-(4-methoxybenzyl)-sn-glycerol 9b
at
0 ЊC. 12-N-(Benzyloxycarbonyl)aminododecanoic acid
(2.27 g, 6.5 mmol) in dry dichloromethane (5 cm3) was trans-
ferred via cannula into the reaction mixture under nitrogen and
stirred at rt overnight. The reaction was quenched by addition
of water (50 cm3) and the aqueous phase was extracted with
dichloromethane (3 × 40 cm3). The combined organic extracts
were washed with brine (20 cm3), dried over MgSO4 and the
solvent was removed in vacuo. Flash chromatography (30–60%
ethyl acetate in hexane) of the residue gave alcohol (ϩ)-8 (3.15
g, 89%) as a white solid: mp 50–51 ЊC (from ethyl acetate);
[α]2D0 = ϩ1.7 (c 0.52 in CHCl3); Rf = 0.48 (50% ethyl acetate in
hexane); νmax (CHCl3)/cmϪ1 3689, 3585, 3540, 3004, 2931, 2856,
1720, 1655, 1612, 1514, 1463, 1454, 1252, 1234, 1174, 1132,
1101 and 1035; δH (400 MHz; CDCl3) 7.35–7.28 (5 H, m, C6H5),
7.25–7.22 (2 H, m, C6H4OMe), 6.88–6.86 (2 H, m, C6H4OMe),
5.08 (2 H, s, OCH2), 4.84 (1 H, br s, NH ), 4.50–4.42 (2 H, m,
OCH2), 4.18–4.00 (2 H, m, CH2CHCH2), 3.99–3.97 (1 H, m,
CH2CHCH2), 3.79 (3 H, s, OCH3), 3.51 (1 H, dd, J 9.6, 4.4,
CH2CHCH2), 3.44 (1 H, J 9.6, 6.0, CH2CHCH2), 3.18–3.13
(2 H, m, CH2NH), 2.70 (1 H, br s, OH ), 2.35–2.28 (2 H, m,
OCOCH2), 1.61–1.56 (2 H, m, CH2CH2NH), 1.47–1.37 (2 H, m,
The alcohol (ϩ)-8 (0.40 g, 0.70 mmol) was lauroylated accord-
ing to procedure as described above for lipid (ϩ)-9a affording
the lipid (ϩ)-9b (0.44 g, 86%) as a white solid (Found: C, 71.3;
H, 9.2; N, 2.1. C43H67O8N requires C, 71.1; H, 9.3; N, 1.9%); mp
41–43 ЊC (from ethyl acetate); [α]2D0 = ϩ6.6 (c 0.8 in CHCl3);
Rf = 0.26 (30% ethyl acetate in hexane); νmax (CHCl3)/cmϪ1 3040,
2927, 2855, 1727, 1513, 1612, 1466, 1255, 1244, 1235, 1174,
1104 and 1035; δH (250 MHz; CDCl3) 7.35 (5 H, s, C6H5), 7.23
(2 H, d, J 8.6, C6H4OMe), 6.87 (2 H, d, J 8.6, C6H4OMe), 5.26–
5.18 (1 H, m, CH2CHCH2), 5.10 (2 H, s, OCH2), 4.49 (1 H,
dd, JAB 11.7, OCHAHB), 4.44 (1 H, dd, JAB 11.7, OCHAHB), 4.33
(1 H, dd, J 11.9, 3.8, CH2CHCH2), 4.16 (1 H, dd, J 11.9,
6.4, CH2CHCH2), 3.80 (3 H, s, OCH3), 3.52 (2 H, d, J 5.1,
CH2CHCH2), 3.16 (2 H, q, J 6.7, CH2NH), 2.31 (2 H, t, J 7.5,
OCOCH2), 2.27 (2 H, t, J 7.5, OCOCH2), 1.61–1.46 (6 H, m,
2 × OCOCH2CH2, CH2CH2NH), 1.55–1.47 (2 H, m, CH2CH2-
CH2NH), 1.26 (28 H, br s, COC11H23, C11H22NH), 0.88 (3 H, t,
J 6.2, CH3); δC (100 MHz; CDCl3) 173.4, 173.1 (2 × OCO),
159.3 (NHCO), 136.7, 129.8, 129.3, 128.5, 128.1, 113.8 (6 ×
C6H5 and C6H5), 72.9 (CH2), 70.4 (CH), 67.9, 66.5, 62.7 (4 ×
1070
J. Chem. Soc., Perkin Trans. 1, 2002, 1067–1075