H. Mizuta et al. / Bioorg. Med. Chem. 10 (2002) 675–683
681
(s, 3Hꢃ2), 2.07 (s, 3H), 3.96 (m, 1H), 4.18 (dd, 1H,
J=11.9 and 2.1 Hz), 4.31 (dd, 1H, J=11.9 and 4.0 Hz),
5.20 (m, 1H), 5.3 (m, 3H), 5.74 (s, 2H), 7.07 (dd, 1H,
J=8.9 and 2.7 Hz), 7.30 (d, 1H, J=2.7 Hz), 7.44 (d, 2H,
J=8.9 Hz), 8.25 (d, 1H, J=8.9 Hz), 8.31 (d, 2H, J=8.9
Hz); 13C NMR(67.5 MHz CDCl 3) d 20.55 (q, 2C), 20.60
(q, 2C), 61.7 (t), 67.2 (t), 67.9 (d), 70.9 (d), 72.4 (d), 72.5
(d), 97.9 (d), 115.6 (d), 116.7 (d), 121.7 (d), 125.4 (d),
128.0 (d), 133.9 (s), 141.8 (s), 145.6 (s), 152.0 (s), 155.2
(s), 160.5 (s), 169.2 (s), 169.3 (s), 170.1 (s), 170.4 (s); IR
(KBr) 1758, 1528 cmꢂ1. Anal. calcd for C28H28N2O17: C
50.61, H 4.25, N 4.22%; found C 50.31, H 4.43, N
4.03%.
(d), 115.3 (d), 115.4 (d), 127.5 (d), 136.2 (s), 141.5 (s),
155.3 (s), 160.3 (s), 169.2 (s), 169.3 (s), 167.0 (s), 170.7
(s), 171.8 (s), 173.0 (s); IR(KBr) 1754, 1584 cmꢂ1. Anal.
calcd for C35H49N3O17 H2O: C 52.43, H 6.41, N 5.24%;
found C 52.36, H 6.12, N 4.82%.
.
1-[5-O-(2,3,4,6-Tetra-O-acetyl-ꢀ-D-glucopyranosyl)-2-ni-
trophenyl] ethoxycarbonyl L-leucyl-L-leucine methyl ester
(9b). Yield 80%; mp 74.0–76.0 ꢁC; H NMR(270 MHz
1
CDCl3) d 0.80–0.94 (m, 12H), 1.51–1.64 (m, 6H), 1.56
(d, 3H, J=6.2Hz), 2.04 (s, 3H), 2.05 (s, 3H), 2.07 (s,
3Hꢃ2), [3.70 (s, 3H), 3.73 (s, 3H)], 4.0–4.3 (m, 4H),
[4.48 (br s, 1H), 4.59 (br s, 1H)], 5.10–5.50 (m, 5H), 6.1–
6.4 (m, 2H), 6.94 (d, 1H, J=9.2Hz), 7.18 (s, 1H), [8.00
(d, 1H, J=9.2Hz), 8.04 (d, 1H, J=9.2Hz)]; 13C NMR
(67.5 MHz CDCl3) d 20.6 (q, 2C), 20.68 (q), 20.76 (q),
[21.71 (q), 21.87 (q)], [22.0 (q), 22.2 (q)], [22.4 (q), 22.7
(q)], 22.8 (q), 24.6 (d), 24.7 (d), 24.8 (q), 41.2 (t), [41.1
(t), 41.5 (t)], [50.7 (d), 50.8 (d)], [52.28 (q), 52.34 (q)],
53.5 (d), [62.1 (t), 62.3 (t)], 68.4 (d), [68.8 (d), 69.2 (d)],
[70.9 (d), 71.1 (d)], 72.2 (d), 72.5 (d), 98.1 (d), [114.2 (d),
115.1 (d)], [115.3 (d), 115.5 (d)], [127.0 (d), 127.4 (d)],
142.1 (s), 142.2 (s), 155.1 (s), [160.2 (s), 160.4 (s)], 169.2
1-[5-O-(2,3,4,6-Tetra-O-acetyl-ꢀ-D-glucopyranosyl)-2-ni-
trophenyl]ethyl 4-nitrophenyl carbonate (8b). Yield 58%
(obtained as a mixture of diastereomers); mp 54–55 ꢁC
1
(from ethanol); H NMR(270 MHz CDCl ) d 1.78 (d,
3
3H, J=6.2 Hz), 2.06 (s, 3H), 2.07 (s, 3H), 2.09 (s,
3Hꢃ2), 2.09 (s, 3H), 4.00 (m, 1H), 4.26 (m, 2H), 5.21 (q,
1H, J=8.9 Hz), 5.33 (s, 3H), 6.49 (q, 1H, J=6.2 Hz),
7.06 (d, 1H, J=8.9 Hz), 7.36 (d, 2H, J=8.1 Hz), 7.41 (s,
1H), 8.09 (d, 1H, J=8.9 Hz), [8.25 (d, 2H, J=8.1 Hz),
8.26 (d, 2H, J=8.1 Hz)]; 13C NMR(67.5 MHz CDCl3)
d 20.41 (q), 20.46 (q, 2C), 20.51 (q), [21.7 (q), 21.9 (q)],
[61.5 (t), 61.7 (t)], 67.7 (d), 67.8 (d), [70.79 (d), 70.83 (d)],
[72.2 (d), 72.4 (d)], 73.2 (d), [97.7 (d), 97.9 (d)], 114.9 (d),
[115.3 (d), 115.7 (d)], 121.5 (d), 125.2 (d), 127.4 (d),
[139.6 (s), 139.7 (s)], [141.9 (s), 142.0 (s)], 145.3 (s), 151.3
(s), 155.1 (s), 160.4 (s), 169.1 (s), 169.2 (s), 167.0 (s),
170.3 (s); IR[?0x81?]iKBr) 1760, 1528 cmꢂ1. Anal. calcd
(s), 169.4 (s), 170.1 (s), 170.7 (s), 171.8 (s), [173.0 (s),
ꢂ1
173.1 (s)]; IR(KBr) 1752, 1522 cm
. Anal. calcd for
C36H51N3O17: C 54.20, H 6.44, N 5.27%; found C
53.91, H 6.43, N 5.25%.
5-O-(2,3,4,6-Tetra-O-acetyl-ꢀ-D-glucopyranosyl)-2-nitro-
benzyloxy carbonyl glycine methyl ester (10a). Yield
51%; mp 59.0–61.0 ꢁC; H NMR(270 MHz CDCl ) d
1
3
.
for C29H30N2O17 0.5H2O: C 50.66, H 4.54, N 4.07%;
found C 50.59, H 4.60, N 4.01%.
2.03 (s, 3H), 2.05 (s, 3H), 2.06 (s, 3H), 2.11 (s, 3H), 3.84
(br s, 1H), 3.84 (s, 3H), 4.21 (s, 3H), 4.47 (br s, 1H), 5.08
(t, 1H, J=3.2Hz), 5.32 (d, 2H, J=8.4Hz), 5.55 (t, 1H,
J=3.2Hz), 5.67 (d, 1H, J=7.8Hz), 5.88 (d, 1H,
J=16.7Hz), 6.05 (br s, 1H), 6.97 (d, 1H, J=8.6Hz), 7.12
(s, 1H), 8.18 (d, 1H, J=8.6Hz); 13C NMR(67.5 MHz
CDCl3) d 20.5 (q), 20.6 (q, 2C), 20.8 (q), 42.5 (t), 52.7
(q), 63.5 (t), 63.6 (t), 69.5 (d), 70.6 (d), 70.7 (d), 72.2 (d),
96.8 (d), 111.6 (d), 116.6 (d), 127.7 (d), 137.4 (s), 140.9
(s), 156.1 (s), 160.9 (s), 169.3 (s), 169.5 (s), 170.1 (s),
171.1 (s), 171.7 (s); IR(KBr) 1752, 1522 cm ꢂ1. Anal.
General procedure for the synthesis of amino acid
derivatives
The synthesis of 1-[5-O-(2,3,4,6-tetra-O-acetyl-b-d-glu-
copyranosyl)-2-nitrophenyl] ethoxy carbonyl l-leucyl-l-
leucine methyl ester (9b) is shown as an example. Com-
pound 8b (1.42 g, 2.09 mmol) and trifluoroacetic acid
salt of LeuLeuOMe (4.60g, 12.4 mmol) in 1,4-dioxane
(20 mL) were treated with triethylamine (6.0 mL, 43
mmol) under Ar at 0 ꢁC. The reaction mixture was stir-
red for 3 days at rt in the dark, and then diluted with
dichloromethane. The mixture was washed with 1 N
HCl, brine, dried over MgSO4, filtered and con-
centrated. The residue was chromatographed on silica
gel (4:1 dichloromethane/AcOEt) to afford 9b as a dia-
stereomeric mixture.
.
calcd for C25H30N2O16 0.5H2O: C 48.16, H 5.01, N
4.49%; found C 48.20, H 4.98, N 4.29%.
1-[5-O-(2,3,4,6-Tetra-O-acetyl-ꢀ-D-glucopyranosyl)-2-ni-
trophenyl] ethoxycarbonyl glycine methyl ester (10b).
Yield 80% (obtained as a diastereomeric mixture); mp
68.0–70.0 ꢁC; 1H NMR(270 MHz CDCl 3) d 1.60 (d, 3H,
J=6.5 Hz), 2.03 (s, 3H), 2.04 (s, 3H), 2.05 (s, 3H), 2.06
(s, 3H), [3.73 (s, 3H), 3.81 (s, 3H)], 3.92 (d, 1H, J=5.1
Hz), 4.1–4.3 (m, 3H), 4.47 (br s, 1H), 5.09 (t, 1H, J=9.5
Hz), 5.33 (m, 2H), 5.56 (t, 1H, J=7.0 Hz), 5.8 (m, 1H),
[6.36 (q, 1H, J=6.5 Hz), 6.40 (q, 1H, J=6.5 Hz)], [6.93
(d, 1H, J=9.2 Hz), 6.96 (d, 1H, J=9.2Hz)], 7.24 (s,
1H), [8.03 (d, 1H, J=9.2 Hz), 8.08 (d, 1H, J=9.2Hz)];
5-O-(2,3,4,6-Tetra-O-acetyl-ꢀ-D-glucopyranosyl)-2-nitro-
benzyloxycarbonyl L-leucyl-L-leucine methyl ester (9a).
Yield 51%; mp 60.0–62.5 ꢁC; 1H NMR(270 MHz
CDCl3) d 0.92–0.99 (m, 12H), 1.55–1.73 (m, 6H), 2.05
(s, 3Hꢃ2), 2.07 (s, 3Hꢃ2), 3.74 (s, 3H), 4.01 (br s, 1H),
4.23 (m, 3H), 4.61 (br s, 1H), 5.14–5.31 (m, 4H), 5.42–
5.47 (m, 1H), 5.61–5.73 (m, 2H), 6.32 (d, 1H, J=7.6
Hz), 6.99 (d, 1H, J=8.6 Hz), 7.20 (s, 1H), 8.17 (d, 1H,
J=8.6 Hz); 13C NMR(67.5 MHz CDCl 3) d 20.5 (q, 2C),
20.6 (q, 2C), 21.8 (q), 21.9 (q), 22.6 (q), 22.8 (q), 24.6
(d), 24.7 (d), 41.2 (t), 41.3 (t), 50.7 (d), 52.2 (q), 53.5 (d),
62.2 (t), 63.4 (t), 68.3 (d), 70.8 (d), 71.9 (d), 72.3 (d), 97.7
13C NMR(67.5 MHz CDCl )d 20.51 (q), 20.54 (q), 20.6
3
(q), 21.0 (q), [21.8 (q), 22.2 (q)], [42.3 (t), 42.4 (t)], [52.3
(q), 52.7 (q)], [61.8 (t), 63.6 (t)], [69.3 (d), 67.0 (d)], 70.8
(d), [70.9 (d), 71.0 (d)], [72.1 (d), 72.4 (d)], [98.1 (d), 98.3
(d)], [111.5 (d), 114.7 (d)], [115.6 (d), 116.8 (d)], [127.2
(d), 127.7 (d)], [141.3 (s), 142.0 (s)], [142.1 (s), 142.8 (s)],
[155.2 (s), 155.6 (s)], [160.4 (s), 161.5 (s)], [169.25 (s),