1206
R. J. Tennant-Eyles et al. / Tetrahedron: Asymmetry 14 (2003) 1201–1210
(c, 0.97 in CHCl3); wmax (CHCl3, thin-film): 3443 (br,
OH) cm−1; lH (400 MHz+COSY, CDCl3): 0.09 (6H, s,
(CH3)2Si), 0.91 (9H, s, (CH3)3CSi), 3.34, 3.62, 3.77 (3H,
3×s, 3×OH), 3.85–3.93 (4H, m, H-3, H-4, H-6, H-6%),
4.12 (1H, m, H-5), 4.21 (1H, s, H-2), 5.54 (1H, d, J1,2
1.1 Hz, H-1), 7.24–7.32 (3H, m, Ar), 7.45–7.48 (2H, m,
Ar); lC (50.3 MHz, CDCl3):−5.5 (q, (CH3)2Si), 18.2 (s,
CHCl3); wmax (CHCl3, thin-film): 3500 (br, OH) cm−1;
lH (400 MHz+COSY, CDCl3): 1.87 (1H, s, OH), 3.77–
3.86 (3H, m, H-3, H-6, H-6%), 3.81, 3.85 (9H, 2×s,
3×CH3OAr), 3.94 (1H, m, H-2), 3.98 (1H, d, J 9.3 Hz,
H-4), 4.07 (1H, m, H-5), 4.53–4.60 (3H, m, CH2Ar),
4.62 (2H, s, CH2Ar), 4.87 (1H, d, J 10.8 Hz, CH2Ar),
5.44 (1H, d, J1,2 1.5 Hz, H-1), 6.84–6.91 (6H, m, Ar),
7.24–7.31 (9H, m, Ar), 7.36–7.39 (2H, m, Ar); lC (50.3
(CH3)3C6 Si), 25.7 (q, (C6 H3)3CSi), 64.1, 69.5, 72.2, 72.3,
MHz, CDCl3): 55.3 (q, 3×C6 H3OAr), 72.0, 72.0, 73.4,
72.9 (4×d, 1×t, C-2, C-3, C-4, C-5, C-6), 88.1 (d, C–1),
127.4, 129.1, 131.6, 134.6 (4×d, Ar-CH); m/z (ES+): 425
74.9 (4×t, C-6, 3×CH2Ar), 73.4, 74.5, 76.0, 79.8 (4×d,
6
(M+K+, 22), 409 (M+Na+, 100), 404 (M+NH4 , 11%);
+
C-2, C-3, C-4, C-5), 99.2 (d, C-1), 114.0, 127.9, 129.3,
129.7, 129.9, 131.9, 132.1 (7×d, Ar-CH), 130.5, 130.7,
134.2, 159.5 (4×s, Ar-C); m/z (FAB+): 655.3 (M+Na+,
25) 121.1 (100%). (Found: C, 67.91; H, 6.68. C36H40O8S
requires C, 68.33; H, 6.37%.)
+
HRMS calcd for C18H34O5SNSi (M+NH4 ) 404.1927.
Found 404.1923.
4.7. Phenyl 6-O-tert-butyldimethylsilyl-2,3,4-tri-O-4-
methoxybenzyl-1-thio-a-D-mannopyranoside, 10
4.9. a-2,2,2-Trichloroethyl-b-carboxy-(phenyl 2,3,4-tri-
O-4-methoxybenzyl-a-
D
-mannopyranos-6-O-yl)-N-9-
-aspartic acid, 13
para-Methoxybenzyl chloride (12.12 ml, 89.3 mmol)
was added to a stirred solution of the triol 9 (8.617 g,
22.3 mmol) in THF (80 ml). The reaction mixture was
cooled to 0°C and sodium hydride (60% dispersion in
silicon oil, 2.679 g, 111.6 mmol) was added portionwise.
Tetrabutylammonium iodide (247 mg, 0.67 mmol) was
added and the mixture was heated under reflux. After
18 h, TLC (hexane:ethyl acetate, 1:1) indicated the
complete conversion of starting material (Rf 0.3) to a
single product (Rf 0.7). The reaction mixture was
quenched with methanol, diluted with DCM (500 ml)
and washed with distilled water (3×200 ml). The
organic phase was dried (MgSO4), filtered and concen-
trated in vacuo. The residue was purified by flash
column chromatography (hexane:ethyl acetate, 5:1) to
give the thioglycoside 10 (10.02 g, 60%) as a clear oil;
[h]2D3 +46.6 (c, 0.7 in CHCl3); wmax (CHCl3, thin-film): no
significant peaks; lH (400 MHz +COSY, CDCl3): 0.09,
0.12 (6H, 2×s, (CH3)2Si), 0.89 (9H, s, (CH3)3CSi), 3.81,
3.82, 3.83 (9H, 3×s, 3×CH3OAr), 3.77–3.89 (2H, m,
obs), 3.91–3.95 (3H, m), 4.06 (1H, m, H-5), 4.47–4.63
(5H, m, CH2Ar), 4.86 (1H, d, J 10.5 Hz, CH2Ar), 5.50
(1H, d, J1,2 1.2 Hz, H-1), 6.82–6.93 (6H, m, Ar),
7.01–7.30 (9H, m, Ar), 7.41–7.44 (2H, m, Ar); lC (50.3
MHz, CDCl3): −5.3, −5.5 (2×q, (CH3)2Si), 18.4 (s,
fluorenylmethoxycarbonyl-
L
Dimethylaminopyridine (29 mg, 0.24 mmol) and dicy-
clohexylcarbodiimide (0.979 g, 4.74 mmol) were added
to a stirred solution of the alcohol 11 (1.499 g, 2.37
mmol) in DCM (20 ml). After
1
h, a-2,2,2-
trichloroethyl-N-9-fluorenylmethoxycarbonyl-
L
-aspartic
acid 1211 (1.731 g, 3.56 mmol) was added and the
reaction mixture was stirred for 7 h when TLC (hex-
ane:ethyl acetate, 2:1) indicated no further conversion
of the starting material (Rf 0.2) to the major product
(Rf 0.3). The reaction mixture was filtered through
Celite® (eluting with DCM) and the solvent removed in
vacuo. The residue was purified by flash column chro-
matography (hexane:ethyl acetate, 2:1) to give the ester
13 (1.881 g, 72% (87% over recovered starting mate-
rial)) as a white foam; [h]2D4 +46.7 (c, 1.0 in CHCl3); wmax
(CHCl3, thin-film): 3339 (br, NH), 1729 (st, CꢀO) 1520
(N–CO) cm−1; lH (400 MHz+COSY, C6D6): 2.70 (1H,
dd, JCH2,CH 4.5 Hz, JCH2,CH2% 17.3 Hz, CH2CH), 2.84
(1H, dd, JCH2%,CH 5.3 Hz, CH%2CH), 3.29, 3.30, 3.31 (9H,
3×s, 3×CH3OAr), 4.00–4.05 (3H, m, CH(Fmoc), H-2,
H-3), 4.14 (1H, a-t, J 9.2 Hz, H-4), 4.26–4.29 (2H, m,
CH2(Fmoc)), CH2Ar), 4.34–4.50 (9H, m, H-5, H-6,
H-6%, CH%2(Fmoc), CH2CCl3, CH2Ar), 4.58 (1H, d, J
10.9 Hz, CH2Ar), 4.69 (1H, m, CH2CH), 4.97 (1H, d, J
10.8 Hz, CH2Ar), 5.68 (1H, s, H-1), 5.79 (1H, d, JNH,CH
8.7 Hz, NH), 6.74–6.83 (6H, m, Ar), 6.98–7.29 (13H, m,
Ar), 7.41–7.55 (6H, m, Ar); lC (50.3 MHz+DEPT,
(CH3)3C
6
), 25.9 (q, (C
6
H3)3CSi), 55.3 (q, 3×C
6 H3OAr),
62.8, 71.4, 71.8, 74.9 (4×t, C-6, 3×C
6
H2Ar), 74.3, 74.6,
76.0, 79.8 (4×d, C-2, C-3, C-4, C-5), 95.7 (d, C-1),
113.9, 127.5, 129.1, 129.5, 129.8, 129.9, 131.8 (7×d,
Ar-CH), 130.2, 131.2, 159.5 (3×s, Ar-C); m/z (FAB+):
769.6 (M+Na+, 15), 121.1 (100%). (Found: C, 67.34; H,
7.41. C42H54O8SSi requires C, 67.53; H, 7.29%.)
CDCl3): 36.2 (t, C
6
H2CH), 47.1, 50.4 (2×d, CH(Fmoc),
H3OBn), 64.2, 67.4, 71.8, 74.8,
CH2CH), 55.3 (q, 3×C
6
6
75.0 (5×t, CH2(Fmoc), C-6, CH2CCl3, 3×CH2Ar), 70.9,
74.3, 75.5, 79.8, 85.8 (5×d, C-1, C-2, C-3, C-4, C-5),
94.6 (s, CCl3), 114.1, 120.3, 125.4, 127.5, 128.0, 129.4,
129.8, 130.1, 131.9 (9×d, Ar-CH), 141.6, 144.0, 156.4,
159.7 (4×s, CꢀO(Fmoc), Ar-C), 169.6, 170.9 (2×s, 2×
CꢀO); m/z (ES+): 1119 (M+NH+4, 100), 692 (55%).
(Found: C, 62.05; H, 5.25; N; 1.27. C57H56O13NSCl3
requires C, 62.15; H, 5.12; N, 1.27%.)
4.8. Phenyl 2,3,4-tri-O-4-methoxybenzyl-1-thio-a-D-
mannopyranoside, 11
Tetrabutylammonium fluoride (16.11 ml, 1.0 M solu-
tion in THF) was added to a stirred solution of thiogly-
coside 10 (10.02 g, 13.4 mmol) in diethyl ether (50 ml)
at 0°C. The mixture was stirred under an atmosphere of
argon for 10 h, when TLC indicated complete conver-
sion of starting material (Rf 0.8) to a single product (Rf
0.5). The reaction mixture was concentrated in vacuo
and the residue was purified by flash column chro-
matography (hexane:ethyl acetate, 2:1) to give the alco-
hol 11 (6.77 g, 79%) as a clear oil; [h]2D3 +55.6 (c, 0.78 in
4.10. b-Carboxy-(phenyl 2,3,4-tri-O-4-methoxybenzyl-a-
D
-mannopyranos-6-O-yl)-N-9-fluorenylmethoxycarbonyl-
L
-aspartic acid, 4
Ester 13 (1.484 g, 1.35 mmol) and zinc powder (529 mg,
8.09 mmol) were stirred in acetic acid:water (9:1, 10 ml)