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A. Marinier et al. / Bioorg. Med. Chem. 9 (2001) 1395–1427
H-50 and H-60), 3.85 (1H, dd, J=6.5, 3.3 Hz, H-20), 4.03
(1H, dd, J=6.5, 2.2 Hz, H-30), 4.22 (1H, dd, J=5.6,
2.2 Hz, H-40), 4.91 (1H, d, J=3.4 Hz, H-10), 5.55–5.60
(2H, m, H-3 and H-4), 5.93 (1H, br dt, H-5), 7.44–7.48,
7.56–7.60 and 8.06–8.08 (5H, 3 sets of m, aromatic H).
2.00 (2Â2H, 2 sets of m, -CH2-CH(CO2H)2 and -CH2-),
2.53 (2H, t, J=7.4 Hz, -NHCOCH2-), 2.76 (2H, dt,
J=6.6, 6.6 Hz,=CH–CH2-), 4.07 (1H, dt, J=9.3,
6.2 Hz, -OCH2-), 4.16 (1H, dt, J=9.3, 6.0 Hz, -OCH2-),
4.23 (1H, dd, J=10.7, 6.6 Hz, H-60), 4.28–4.35 and
4.43–4.55 (7H, 2 sets of m, H-1, H-20, H-30, H-40, H-60,
H-50 and -CH(CO2H)2), 4.38 (1H, dd, J=10.4, 4.8 Hz,
H-1), 5.17–5.22 (1H, m, H-2), 3.52 (1H, d, J=3.5 Hz,
H-10), 5.92 (1H, dd, J=15.4, 7.3 Hz, H-4), 6.08 (1H, dt,
J=15.4, 6.6 Hz, H-5), 6.29 (1H, br t, H-3), 7.36–7.40,
7.45–7.49 and 8.24–8.28 (5H, 3 sets of m, aromatic H),
1
ꢀ-Anomer: H NMR (400 MHz, CDCl3) d 0.06 (6H, s,
-Si(CH3)2), 0.89 (12H, m, -SitBu and -CH3), 1.24 (20H,
m, -(CH2)10-), 1.31 (3H, s, -C(CH3)2), 1.34–1.50 (2H, m,
-CH2-), 1.44 and 1.45 (18H, 2 s , 2Â-OtBu), 1.51 (3H, s,
-C(CH3)2), 2.04–2.14 (4H, m, ¼CH-CH2- and -CH2-
CH(CO2tBu)2), 3.24 (1H, t, J=7.3 Hz, -CH(CO2tBu)2),
3.42 (1H, br dd, H-20), 3.61 (1H, dd, J=10.3, 5.0 Hz, H-
1), 3.70–3.76 (2H, m, H-2 and -OCH2-), 3.78–3.93 (1H,
m, -OCH2-), 3.80 (1H, dd, J=10.0, 5.8 Hz, H-60), 3.86
(1H, dd, J=10.0, 7.2 Hz, H-60), 3.90 (1H, dd, J=10.2,
7.7 Hz, H-1), 4.01–4.06 (2H, m, H-30 and H-50), 4.16
(1H, dd, J=5.6, 1.8 Hz, H-40), 4.20 (1H, d, J=7.8 Hz,
H-10), 5.56 (1H, dd, J=14.8, 8.0 Hz, H-4), 5.62 (1H, dd,
J=8.0, 4.0 Hz, H-3), 5.93 (1H, dt, J=14.8, 6.7 Hz, H-5),
7.42–7.46, 7.55–7.58 and 8.05–8.07 (5H, 3 sets of m,
aromatic H).
1
8.80 (1H, d, J=8.6 Hz, -NH-). Sodium salt: H NMR
(400 MHz, CD3OD) d 0.83 (6H, m, 2Â-CH3), 1.21–1.39
(46H, m, -(CH2)13- and -(CH2)10), 1.53 (2H, m, -CH2-),
1.98–2.19 (6H, m, -NHCOCH2-, ¼CH-CH2- and -CH2-
CH(CO2Na)2), 5.21 (1H, t, J=6.9 Hz, -CH(CO2Na)2),
3.46–3.80 (10H, m, H-1, H-20, H-30, H-40, H-50, H-60 and
-OCH2-), 4.35 (1H, m, H-2), 4.88 (1H, d, J=2.5 Hz, H-
10), 5.46 (1H, dd, J=14.8, 8.0 Hz, H-4), 5.53 (1H, br t,
H-3), 5.84 (1H, dt, J=14.8, 6.4 Hz, H-5), 7.39–7.43,
7.51–7.55 and 7.96–7.98 (5H, 3 sets of m, aromatic H).
IR (film) ꢀmax (cmÀ1) 3700–3000 (NH), 2920, 2850 (C–
H), 1720, 1650, 1600 (C¼O).
(2S,3R,4E)-3-Benzoyloxy-2-hexadecanoylamino-1-[2-O-
(3,3-di-tert-butyloxycarbonylpropyl)-3,4-O-isopropylidene-
6-O-tert-butyldimethylsilyl-ꢁ-D-galactopyranosyloxy]-4-
octadecene 32a. (2S,3R,4E)-3-Benzoyloxy-2-azido-1-[2-
O-(3,3-di-tert-butyloxycarbonylpropyl)-3,4-O-isopropyl-
idene-6-O-tert-butyldimethylsilyl-a-d-galactopyranosy-
loxy]-4-octadecene 31a (0.230 g, 0.233 mmol) was reac-
ted by the procedure used to synthesize compound 30a
and afforded the title compound (0.168 g, 60%) as an
oil. [a]2D2 +40ꢁ (c 1.0, CHCl3). 1H NMR (400 MHz,
CDCl3) d 0.07 (6H, s, -Si(CH3)2), 0.90 (15H, m, -SitBu
and 2Â-CH3), 1.25–1.27 (46H, m, -(CH2)10 and
-(CH2)13-), 1.31 (3H, s, -C(CH3)2), 1.43 and 1.45 (18H, 2
s, -OtBu), 1.46 (3H, s, -C(CH3)2), 1.49–1.62 (4H, m,
-CH2- and -CH2-CH(CO2tBu)2), 2.00–2.09 and 2.13–
2.22 (2Â2H, 2 sets of m, -NHCOCH2- and ¼CH–CH2-),
3.40 (1H, dd, J=6.3, 3.3 Hz, H-20), 3.46 (1H, t,
J=7.5 Hz, -CH(CO2tBu)2), 3.57–3.70 (3H, m, -OCH2-
and H-1), 3.74 (1H, dd, J=9.8, 6.3 Hz, H-60), 3.83 (1H,
dd, J=9.8, 7.1 Hz, H-60), 3.88 (1H, dd, J=10.6, 3.6 Hz,
H-1), 4.00 (1H, br dd, H-50), 4.18–4.21 (2H, m, H-30 and
H-40), 4.49 (1H, m, H-2), 4.79 (1H, d, J=3.2 Hz, H-10),
5.54 (1H, dd, J=15.3, 7.5 Hz, H-4), 5.65 (1H, br t, H-3),
5.89 (1H, dt, J=15.3, 6.7 Hz, H-5), 6.59 (1H, d,
J=8.8 Hz, -NH-), 7.42–7.46, 7.53–7.58 and 8.03–8.05
Synthesis of (2S,3R,4E)-3-benzoyloxy-2-hexadecanoyl-
amino-1-[2-O-(5,5-dicarboxypentyl)-3-O-benzoyl-ꢁ-D-ga-
lactopyranosyloxy]-4-octadecene 41a. (2S,3R,4E)-3-
Benzoyloxy-2-azido-1-[2-O-(5,5-di-tert-butyloxycarbonyl-
pentyl)-3-O-benzoyl-4,6-O-benzylidene-ꢁ-D-galactopyra-
nosyloxy]-4-octadecene 36a and (2S,3R,4E)-3-benzoyl-
oxy-2-azido-1-[2-O-(5,5-di-tert-butyloxycarbonylpentyl)-3
-O-benzoyl-4,6-O-benzylidene-ꢀ-D-galactopyranosyloxy]-
4-octadecene 36b. Ethyl 3-O-benzoyl-4,6-O-benzylidene
-2-O-(5,5-di-tert-butyloxycarbonylpentyl)-1-thio-b-d-
galactopyranoside 18 (0.780 g, 1.12 mmol) and
(2S,3R,4E)-2-azido-3-benzoyloxy-4-octadecen-1-ol 28
(0.423 g, 0.99 mmol) were reacted by the procedure used
to synthesize compounds 29a and b and afforded the
a-anomer ot the title compound (0.630 g, 60%) and the
b-anomer of the title compound (ꢀ300 mg, ꢀ29%) as
yellow oils. ꢁ-Anomer: 1H NMR (400 MHz, CDCl3)
d 0.88 (3H, t, J=6.8 Hz, -CH3), 1.25–1.38 (22H, m,
-(CH2)11-), 1.42 (18H, s, 2Â-OtBu), 1.42–1.44, 1.51–1.57
and 1.68–1.74 (3Â2H, 3m, -(CH2)3-), 2.09 (2H, dt,
J=6.8, 6.8 Hz, ¼CH-CH2-), 2.96 (1H, t, J=7.5 Hz,
-CH(CO2tBu)2), 3.55–3.48 (3H, m, H-1 and -OCH2-),
3.87 (1H, dd, J=10.8, 4.2 Hz, H-1), 3.88 (1H, br s, H-
50), 4.03 (1H, m, H-2), 4.09 (1H, dd, J=12.5, 1.2 Hz, H-
60), 4.12 (1H, dd, J=10.5, 3.4 Hz, H-20), 4.29 (1H, dd,
J=12.5, 0.7 Hz, H-60), 4.61 (1H, d, J=3.5 Hz, H-40),
5.18 (1H, d, J=3.4 Hz, H-10), 5.45 (1H, dd, J=10.5,
3.5 Hz, H-30), 5.52 (1H, s, -OCHO-), 5.57–5.66 (2H, m,
H-3 and H-4), 5.97 (1H, dt, J=14.4, 6.8 Hz, H-5), 7.34–
7.36, 7.44–7.49, 7.55–7.60 and 8.06–8.08 (15H, 4 sets of
m, aromatic H). IR (CH2Cl2) ꢀmax (cmÀ1) 2920, 2850
(C–H), 1720 (C¼O). Anal. calcd for C60H83N3O13: C,
68.35; H, 7.93; N, 3.99. Found: C, 68.19; H, 7.79; N,
4.03. ꢀ-Anomer: 1H NMR (400 MHz, CDCl3) d 0.89
(3H, t, J=6.8 Hz, -CH3), 1.12–1.33 (22H, m, -(CH2)11-),
1.38–1.46 (2H, m, -CH2-), 1.41 and 1.42 (18H, 2s,
2Â -OtBu), 1.47–1.60 (2H, m, -CH2-), 1.62–1.70 (2H,
m, -CH2-), 2.09 (2H, dt, J=6.9, 6.9 Hz, ¼CH-CH2-),
2.90 (1H, t, J=7.5 Hz, -CH(CO2tBu)2), 3.54 (1H, s, H-
(5H, 3 sets of m, aromatic H). IR (film) ꢀmax (cmÀ1
)
3290 (NH), 2920, 2850 (C-H), 1740, 1715, 1640 (C¼O).
Anal. calcd for C69H121NO13Si: C, 69.02; H, 10.16; N,
1.17. Found: C, 69.05; H, 10.12; N, 1.23.
(2S,3R,4E)-3-Benzoyloxy-2-hexadecanoylamino-1-[2-O-
(3,3-di-carboxypropyl)-ꢁ-D-galactopyranosyloxy]-4-octa-
decene 34a. (2S,3R,4E)-3-Benzoyloxy-2-hexadecanoyl-
amino-1-[2-O-(3,3-di-tert-butyloxycarbonylpropyl)-3,4-O-
isopropylidene-6-O-tert-butyldimethylsilyl-a-d-galacto-
pyranosyloxy]-4-octadecene 32a (0.155 g, 0.129 mmol)
was reacted by the procedure used to synthesize com-
pound 33a and afforded the title compound (0.081 g,
67%) as a beige solid. Diacid: 1H NMR (400 MHz,
pyridine-d5) d 0.85 (6H, t, J=6.7 Hz, 2Â-CH3), 1.23–
1.39 (46H, m, -(CH2)13- and -(CH2)10-), 1.81–1.90 and