S. Garneau et al. / Bioorg. Med. Chem. 12 (2004) 6473–6494
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dure as that employed for the synthesis of 24a, using tri-
chloroacetonitrile (2mL, 20.0mmol) in pyridine (3mL)
to give the desired compound (138mg, 93%) as a glassy
solid: IR (CH2Cl2 cast) 3279, 2954, 2929, 1747, 1665,
3316, 2930, 1745, 1661, 1455 1499cmꢀ1
;
1H NMR
(CD3OD, 360MHz) d 7.37 (m, 5H), 5.29 (t, 1H,
J = 9.7Hz), 5.20 (ABq, 1H, J = 12.0Hz), 5.18 (ABq,
1H, J = 12.0Hz), 5.12 (t, 1H, J = 9.5Hz), 4.95 (t, 1H,
J = 9.7Hz), 4.76 (d, 1H, J = 8.4Hz), 4.52 (m, 2H), 4.41
(dd, 1H, J = 12.4, 3.7Hz), 4.06 (m, 5H), 3.77 (m, 4H),
3.65 (m, 3H), 3.49 (m, 2H), 2.07 (s, 3H), 2.04 (s, 6H),
1.97, 1.96, 1.91, and 1.89 (4s, 4 · 3H), 1.75–1.11 (m,
14H), 0.87 (m, 9H); 13C NMR (CD3OD, 100MHz) d
173.6, 173.4, 172.4, 172.2, 172.0, 171.8, 171.6, 171.3,
137.2, 129.7, 129.4, 101.9, 101.8, 79.6 (d, J = 7.1Hz),
77.7, 74.9, 74.0, 73.6, 72.8, 70.6, 70.3 (d, J = 16.6Hz),
69.9, 68.0, 65.9 (d, J = 5.0Hz), 63.8, 63.0, 56.3, 55.5,
40.5, 38.4, 37.8, 30.9, 29.1, 25.8, 24.0 (br), 23.3 (d,
J = 137.2Hzz), 23.1, 23.0, 22.9, 21.1, 20.8, 20.7, 20.6,
20.5, 20.0; 31P NMR (CD3OD, 81MHz) d 30.9; LRMS
(FAB, Cleland) m/z (relative intensity) 1113.5 (MK+,
0.7%), 1097.5 (MNa+, 1.6%), 1075.5 (MH+, 0.6%).
1368, 1231, 1044cmꢀ1 1H NMR (CD2Cl2–CD3OD,
;
400MHz) d 7.40–7.30 (m, 5H), 5.20–5.12 (m, 3H), 5.00
(dd, 1H, J = 10.0, 9.5Hz), 4.50 (d, 1H, J = 8.5Hz),
4.28–4.20 (m, 3H), 4.15–4.06 (m, 2H), 3.80–3.65 (m,
4H), 3.53–3.40 (m, 2H), 2.04, 1.99, 1.98, and 1.90 (4s,
4 · 3H), 1.85–1.05 (m, 14H), 0.86 and 0.84 (2d, 9H,
J = 7.0Hz); 13C NMR (CD2Cl2–CD3OD, 100MHz) d
172.1, 171.3, 171.1, 170.5, 170.1, 135.8, 129.0, 128.8,
128.6, 100.8, 78.6 (d, J = 7.1Hz), 73.1, 72.0, 70.3, 69.9
(d, J = 14.6Hz), 69.2, 67.4, 64.9 (d, J = 5.4Hz), 62.6,
54.2, 39.6, 37.6, 36.9, 30.1, 28.3, 25.0, 22.8, 22.7, 22.6,
22.0 (d, J = 108.5Hz), 20.8, 20.7, 19.6; 31P NMR
(CD2Cl2, 162MHz) d 34.5; LRMS (FAB, Cleland) m/z
(relative intensity) 811 (MNa+, 0.5%), 789 (MH+,
1.4%), 119 (100%).
4.42. (R)-3-[3-O-(2-Acetamido-3,4,6-tri-O-acetyl-2-
deoxy-b-D-glucopyranosyl-(1fi4)-2-acetamido-3,6-di-O-
acetyl-2-deoxy-b-D-glucopyranosyl)propylphosphinato]-2-
octyloxypropanoic acid (30b)
4.40. Benzyl (R)-3-[3-O-(2-acetamido-3,4,6-tri-O-acetyl-
2-deoxy-b-D-glucopyranosyl-(1fi4)-2-acetamido-3,6-di-
O-acetyl-2-deoxy-b-D-glucopyranosyl)propylphosphi-
nato]-2-octyloxypropanoate (29b)
A solution of 29b (35mg, 0.03mmol) in acetic acid–95%
EtOH (1:1 v/v) (2mL) was stirred under H2 in the pres-
ence of 10% Pd/C (12mg) for 6h. The mixture was fil-
Compound 29b was prepared from 28c (55mg,
0.07mmol) and 11a (68mg, 0.2mmol) by the same meth-
od as that employed for the synthesis of 24a, using tri-
chloroacetonitrile (1.1mL, 11.0mmol) in pyridine
(4mL). Purification by flash chromatography (SiO2,
CH2Cl2–MeOH, gradient elution, 20:1 to 1:1) gave 29b
(60mg, 79%) as a tan solid: IR (CH2Cl2 cast) 3304,
tered through a Millex-HV lm filter and then
concentrated in vacuo to give 30b (33mg, quant.) as a
white solid: IR (MeOH cast) 3325, 2871, 1700, 1661,
1
1539, 1456, 1437cmꢀ1; H NMR (CD3OD, 360MHz) d
5.29 (t, 1H, J = 9.8Hz), 5.12 (t, 1H, J = 9.5Hz), 4.95 (t,
1H, J = 9.6Hz), 4.76 (d, 1H, J = 8.3Hz), 4.54 (m, 2H),
4.43 (dd, 1H, J = 12.4, 3.7Hz), 4.04 (m, 5H), 3.80 (m,
4H), 3.67 (m, 3H), 3.52 (m, 2H), 2.09, 2.05, 2.04, 1.97,
1.96, 1.93, and 1.90 (7s, 7 · 3H), 1.79 (m, 2H), 1.61 (m,
4H), 1.29 (m, 10H), 0.89 (t, 3H, J = 6.6Hz); 13C NMR
(CD3OD, 100MHz) d 175.2, 173.6, 172.4, 172.2, 172.0,
171.8, 171.3, 102.0, 101.7, 81.2 (br), 77.8, 74.8, 74.0,
73.8, 72.8, 72.2 (br), 71.3 (br), 69.8, 65.8 (br), 63.9,
63.0, 56.2, 55.5, 33.0, 30.7, 30.6, 30.4, 27.1, 24.7 (br),
23.6 (d, J = 141.5Hz), 23.0, 22.9, 21.1, 20.9, 20.7, 20.6,
20.5, 14.5; 31P NMR (CD3OD, 162MHz) d 25.1; LRMS
(FAB, Cleland) m/z (relative intensity) 995.4 (MK+,
4.7%), 979.1 (MNa+, 3.4%), 957.2 (MH+, 1.0%).
2953, 1747, 1659, 1499cmꢀ1
;
1H NMR (CD3OD,
400MHz) d 7.36 (m, 5H), 5.29 (dd, 1H, J = 10.4,
9.4Hz), 5.21 (ABq, 1H, J = 12.1Hz), 5.19 (ABq, 1H,
J = 12.1Hz), 5.10 (dd, 1H, J = 10.3, 8.9Hz), 4.94 (t,
1H, J = 9.6Hz), 4.76 (d, 1H, J = 8.3Hz), 4.49 (m, 2H),
4.41 (dd, 1H, J = 12.5, 3.9Hz), 4.19 (m, 3H), 4.04 (m,
2H), 3.79 (m, 4H), 3.64 (m, 3H), 3.48 (m, 2H), 2.08,
2.04, 2.03, 1.97, 1.96, 1.90, and 1.89 (7s, 7 · 3H), 1.74
(m, 2H), 1.54 (m, 4H), 1.28 (m, 10H), 0.89 (t, 3H,
J = 6.7Hz); 13C NMR (CD3OD, 100MHz) d 173.6,
172.4, 172.2, 172.0, 171.8, 171.2, 137.2, 129.7, 129.4,
102.0, 101.6, 80.3 (d, J = 6.4Hz), 77.7, 74.9, 74.1, 73.7,
72.8, 72.2, 70.9 (d, J = 16.5Hz), 69.9, 67.9, 65.3 (br),
63.9, 63.0, 56.3, 55.6, 33.0, 30.8, 30.5, 30.4, 27.1, 24.7
(d, J = 4.8Hz), 24.2 (d, J = 140.5Hz), 23.7, 23.0, 22.9,
21.1, 20.9, 20.7, 20.6, 20.5, 14.5; 31P NMR (CD3OD,
81MHz) d 26.1; LRMS (FAB, Cleland) m/z (relative
intensity) 1047.1 (MH+, 1.9%).
4.43. (2R,30R)-3-[3-O-(2-Acetamido-3,4,6-tri-O-acetyl-2-
deoxy-b-D-glucopyranosyl-(1fi4)-2-acetamido-3,6-di-O-
acetyl-2-deoxy-b-D-glucopyranosyl)propylphosphinato]-2-
(30,70-dimethyloctyloxy)propanoic acid (30c)
4.41. Benzyl (2R,30R)-3-[3-O-(2-acetamido-3,4,6-tri-O-
acetyl-2-deoxy-b-D-glucopyranosyl-(1fi4)-2-acetamido-
3,6-di-O-acetyl-2-deoxy-b-D-glucopyranosyl)propyl-
phosphinato]-2-(30,70-dimethyloctyloxy)propanoate (29c)
The procedure used for the synthesis of 29b was fol-
lowed. Reaction of 29c (35mg, 0.03mmol) with 10%
Pd/C (17mg) in acetic acid–95% EtOH (1:1 v/v) (3mL)
over 3.25h gave 30c (27mg, quant.) as colorless solid:
1
IR (MeOH cast) 3335, 2927, 1748, 1617, 1456cmꢀ1; H
Compound 29c was synthesized in 4days from 28c
(37mg, 0.05mmol) and 11b (34mg, 0.1mmol) in the
same manner as 24a was prepared from 23 and 11a,
using trichloroacetonitrile (0.75mL, 7.5mmol) in pyr-
idine (2mL). Purification by flash chromatography
(SiO2, CH2Cl2–MeOH, gradient elution, 40:1 to 7:3) af-
forded 29c (38mg, 72%) as a tan solid: IR (MeOH cast)
NMR (CD3OD, 400MHz) d 5.29 (t, 1H, J = 10.0Hz),
5.13 (t, 1H, J = 9.1Hz), 4.96 (t, 1H, J = 9.6Hz), 4.76
(d, 1H, J = 8.4Hz), 4.54 (m, 2H), 4.43 (dd, 1H,
J = 12.4, 3.7Hz), 4.15–4.00 (m, 5H), 3.86–3.63 (m, 7H),
3.54 (m, 2H), 2.09 (s, 3H), 2.05 (s, 6H), 1.98, 1.96, 1.93,
and 1.90 (4s, 4 · 3H), 1.82–1.11 (m, 14H), 0.89 (t, 9H,
J = 6.6Hz); 13C NMR (CD3OD, 100MHz) d 173.6,