A R T I C L E S
Dumoulin et al.
1
ppm. Anal. Calcd for C53H65N3O11: C, 69.18; H, 7.12; N, 4.57.
Found: C, 68.64; H, 7.24; N, 4.58.
procedure; 678 mg (57%); [R]D ) +49.4° (c 0.8, CHCl3); H NMR
chemical shifts are identical with those of compound 8a (0.10 ppm
(coupling constants (0.1 Hz), and 13C chemical shifts are identical
with those of compound 8a (0.5 ppm. Anal. Calcd for C67H93NO12:
C, 72.86; H, 8.49; N, 1.27. Found: C, 73.23; H, 8.64; N, 1.45.
General Procedure for the Synthesis of Compounds 8a,c, 9b,c,
and 10a-c. The acid chloride (1.5 equiv) was added, under argon, to
a stirred solution of the azide 7 (1 equiv, 1 mmol/8 mL) in freshly
distilled benzene containing activated 4 Å molecular sieves (0.2 g/mL).
A solution of triphenylphosphine in benzene (1.5 equiv, 1 mmol/mL)
was added dropwise to the reaction mixture, which was then stirred
for 48 h, at which time the reaction appeared to have reached completion
by TLC. The reaction mixture was filtered through Celite and
concentrated in vacuo to a gum, which was purified by silica gel column
chromatography (1:1 or 2:1 petroleum ether/ethyl acetate) to give the
expected product.
3-O-(2,3,4,6-Tetra-O-benzoyl-â-D-galactopyranosyl)-2-deoxy-1-O-
hexadecyl-2-octadecanamido-sn-glycerol (10c): obtained as an amor-
phous solid from 7c and octadecanoyl chloride following the general
1
procedure; 414 mg (57%); [R]D ) +37.4° (c 0.9, CHCl3); H NMR
chemical shifts are identical with those of compound 8a (0.10 ppm
(coupling constants (0.1 Hz), and 13C chemical shifts are identical
with those of compound 8a (0.5 ppm. Anal. Calcd for C71H101NO12:
C, 73.48; H, 8.77; N, 1.21. Found: C, 73.14; H, 8.91; N, 1.28.
3-O-(2,3,4,6-Tetra-O-benzoyl-â-D-galactopyranosyl)-2-deoxy-2-
hexanamido-1-O-hexyl-sn-glycerol (8a): obtained from 7a and hex-
anoyl chloride, following the general procedure, as an amorphous solid;
General Procedure for the Synthesis of Compounds 11a,c, 12b,c,
and 13a-c. A catalytic amount of sodium (0.1 equiv) was dissolved
in a solution of the benzoylated compound in either methanol or 1:1
chloroform/methanol (1 equiv, 1 mmol/20 mL), and the mixture was
then stirred for 18 h, at room temperature. The deprotected product
was filtered and adsorbed on silica gel, and the cake was deposited at
the top of a column of silica gel for chromatographic purification (8:1
dichloromethane/methanol) to give the expected product. Due to the
poor solubility of the products in all normal bench solvents, [R]D values
were not determined.
1
621 mg (45%); [R]D ) +42.2° (c 0.8, CHCl3); H NMR (CDCl3) δ
8.21-7.31 (m, 20 H, aromatics), 5.91 (bd, 1H, H-4′, J3′,4′ ) 3.1 Hz),
5.72 (dd, 1H, H-2′, J1′,2′ ) 7.6 Hz, J2′,3′ ) 10.4 Hz), 5.64 (dd, 2H,
H-3′, NH), 4.83 (d, 1H, H-1′), 4.61 (dd, 1H, H-6′a, J5′,6′a ) 6.1 Hz,
J6′a,6′b ) 10.6 Hz), 4.47-4.25 (m, 3H, H-2, H-5′, H-6′b), 4.11 (dd, H-3a),
3.71 (dd, 1H, H-3b), 3.47-3.23 (m, 4H, H-1a, H-1b, OCH2CH2), 2.31
(t, 2H, NHCOCH2), 1.42 (t, 2H, OCH2CH2), 1.25 (bs, 12H, 6 CH2),
0.88 (t, 6H, 2 CH3); 13C NMR (CDCl3) δ 172.78 (CONH), 166.04,
165.58, 165.54, 165.35 (CdO), 133.65, 133.49, 133.32 (CIV, aromatics),
130.06, 129.83, 129.80, 129.77, 129.45, 129.25, 129.10, 128.82, 128.69,
128.56, 128.50, 128.33 (CH, aromatics), 101.85 (C-1′), 71.53-71.45
(C-3′, C-5′), 71.33, 68.65 (C-1, OCH2), 70.12 (C-2′), 68.49 (C-3), 68.14
(C-4′), 62.05 (C-6′), 48.09 (C-2), 36.49 (NHCOCH2), 31.97-22.40
((CH2)n), 14.18-13.99 (2 CH3). Anal. Calcd for C49H57NO12: C, 69.08;
H, 6.74; N, 1.64. Found: C, 69.38; H, 6.80; N, 1.72.
3-O-(2,3,4,6-Tetra-O-benzoyl-â-D-galactopyranosyl)-2-deoxy-1-O-
hexadecyl-2-hexanamido-sn-glycerol (8c): obtained from 7c and
hexanoyl chloride, following the general procedure, as an amorphous
solid; 300 mg (49%); [R]D ) +57.7° (c 1.0, CHCl3); 1H NMR chemical
shifts are identical with those of compound 8a (0.10 ppm (coupling
constants (0.1 Hz), and 13C chemical shifts are identical with those of
compound 8a (0.5 ppm. Anal. Calcd for C59H77NO12: C, 71.42; H,
7.82; N, 1.41. Found: C, 71.65; H, 8.08; N, 1.56.
2-Deoxy-3-O-â-D-galactopyranosyl-2-hexanamido-1-O-hexyl-sn-
glycerol (11a): obtained from 8a, as a white amorphous solid; 149 mg
1
(85%); H NMR (CDCl3) δ 6.52 (bd, 1H, NH), 4.73-4.49 (2 bs, 2H,
2 OH), 4.28-2.04 (m, 18H, 2 OH, H-1′, H-2′, H-3′, H-4′, H-5′, H-6a′,
H-6b′, H-1a, H-1b, H-2, H-3a, H-3b, OCH2CH2, NHCOCH2), 1.54 (bs,
2H, OCH2CH2), 1.26 (bs, 12H, 6 CH2), 0.88 (t, 6H, 2 CH3); 13C NMR
(CDCl3) δ 174.23 (CdO), 104.36 (C-1′), 74.68, 73.68 (C-3′, C-5′),
71.50 (C-3), 71.21 (C-2′), 69.57, 69.10 (C-1, OCH2CH2), 68.64 (C-
4′), 61.06 (C-6′), 48.86 (C-2), 36.62 (NHCOCH2), 31.69-22.44
((CH2)n), 14.06, 14.00 (2 CH3). Anal. Calcd for C21H41NO8: C, 57.91;
H, 9.49; N, 3.22. Found: C, 58.24; H, 9.87; N, 3.22.
2-Deoxy-3-O-â-D-galactopyranosyl-1-O-hexadecyl-2-hexanamido-
sn-glycerol (11c): obtained from 8c, as a white solid; 150 mg (78%);
1H and 13C NMR chemical shifts are identical with those of compound
11a (0.1 and (1.0 ppm, respectively. Anal. Calcd for C31H61NO8: C,
64.66; H, 10.69; N, 2.43. Found: C, 64.33; H, 10.80; N, 2.53.
3-O-(2,3,4,6-Tetra-O-benzoyl-â-D-galactopyranosyl)-2-deoxy-2-
dodecanamido-1-O-dodecyl-sn-glycerol (9b): obtained from 7b and
dodecanoyl chloride, following the general procedure, as an amorphous
solid; 700 mg (40%); [R]D ) +50.9° (c 0.8, CHCl3); 1H NMR chemical
shifts are identical with those of compound 8a (0.10 ppm (coupling
constants (0.1 Hz), and 13C chemical shifts are identical with those of
compound 8a (0.5 ppm. Anal. Calcd for C61H81NO12: C, 71.81; H,
8.00; N, 1.37. Found: C, 71.86; H, 8.13; N, 1.44.
2-Deoxy-2-dodecanamido-1-O-dodecyl-3-O-â-D-galactopyranosyl-
sn-glycerol (12b): obtained from 9b, as a white solid; 241 mg (89%);
1H and 13C NMR chemical shifts are identical with those of compound
11a (0.1 and (1.0 ppm, respectively. Anal. Calcd for C33H65NO8: C,
65.64; H, 10.85; N, 2.32. Found: C, 65.14; H, 10.73; N, 2.40.
2-Deoxy-2-dodecanamido-3-O-â-D-galactopyranosyl-1-O-hexa-
decyl-sn-glycerol (12c): obtained from 9c, as a white solid; 228 mg
1
(83%); H NMR (C5D5N) δ 8.48 (bd, 1H, NH), 6.79 (bs, 1H, OH),
3-O-(2,3,4,6-Tetra-O-benzoyl-â-D-galactopyranosyl)-2-deoxy-2-
dodecanamido-1-O-hexadecyl-sn-glycerol (9c): obtained as an amor-
phous solid from 7c and dodecanoyl chloride following the general
6.52 (m, 2H, 2 OH), 4.88-2.37 (m, 17H, OH, H-1′, H-2′, H-3′, H-4′,
H-5′, H-6a′, H-6b′, H-1a, H-1b, H-2, H-3a, H-3b, OCH2CH2, NH-
COCH2), 1.54 (bs, 2H, OCH2CH2), 1.27 (bs, 44H, 22 CH2), 0.87 (t,
6H, 2 CH3); 13C NMR (C5D5N) δ 173.54 (CdO), 106.60 (C-1′), 77.30,
75.57 (C-3′, C-5′), 72.89 (C-2′), 71.58 (C-3), 70.38, 70.31 (C-1, OCH2-
CH2), 70.30 (C-4′), 62.51 (C-6′), 50.09 (C-2), 36.88 (NHCOCH2),
32.29-23.16 ((CH2)n), 14.47 (2 CH3). Anal. Calcd for C37H73NO8: C,
67.33; H, 11.15; N, 2.12. Found: C, 66.88; H, 11.21; N, 2.39.
1
procedure; 443 mg (45%); [R]D ) +48.4° (c 0.76, CHCl3); H NMR
chemical shifts are identical with those of compound 8a (0.10 ppm
(coupling constants (0.1 Hz), and 13C chemical shifts are identical
with those of compound 8a (0.5 ppm. Anal. Calcd for C65H89NO12:
C, 72.53; H, 8.33; N, 1.30. Found: C, 72.29; H, 8.56; N, 1.18.
3-O-(2,3,4,6-Tetra-O-benzoyl-â-D-galactopyranosyl)-2-deoxy-1-O-
hexyl-2-octadecanamido-sn-glycerol (10a): obtained as an amorphous
solid from 7a and octadecanoyl chloride following the general
2-Deoxy-3-O-â-D-galactopyranosyl-1-O-hexyl-2-octadecanamido-
sn-glycerol (13a): obtained as a white solid from 10a; 205 mg (77%);
1H and 13C NMR chemical shifts are identical with those of compound
11a (0.1 and (1.0 ppm, respectively. Anal. Calcd for C33H65NO8: C,
65.64; H, 10.85; N, 2.32. Found: C, 65.54; H, 11.06; N, 2.50.
1
procedure; 345 mg (58%); [R]D ) +55.5° (c 0.8, CHCl3); H NMR
chemical shifts are identical with those of compound 8a (0.10 ppm
(coupling constants (0.1 Hz), and 13C chemical shifts are identical
with those of compound 8a (0.5 ppm. Anal. Calcd for C61H81NO12:
C, 71.81; H, 8.00; N, 1.37. Found: C, 72.03; H, 8.10; N, 1.31.
3-O-(2,3,4,6-Tetra-O-benzoyl-â-D-galactopyranosyl)-2-deoxy-1-O-
dodecyl-2-octadecanamido-sn-glycerol (10b): obtained as an amor-
phous solid from 7b and octadecanoyl chloride following the general
2-Deoxy-1-O-dodecyl-3-O-â-D-galactopyranosyl-2-octadecanamido-
sn-glycerol (13b): obtained as a white solid from 10b; 284 mg (70%);
1H and 13C NMR chemical shifts are identical with those of compound
12c (0.2 and (1.1 ppm, respectively. Anal. Calcd for C39H77NO8: C,
68.08; H, 11.28; N, 2.04. Found: C, 68.07; H, 11.63; N, 1.94.
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13742 J. AM. CHEM. SOC. VOL. 124, NO. 46, 2002