G. A. van der Marel et al.
72.6, 68.6, 64.3, 63.3, 56.9, 22.7, 19.1 ppm; ESI-HRMS: calcd for
C23H31N3O5Si [M+H]: 458.2106; found: 458.2126. The diol was dissolved
in DMF (7 mL) and trimethyl orthoacetate (640 mL, 3.29 mmol) and
CSA (cat.) were added. After stirring for 1 h, the mixture was neutralised
with Et3N, taken up in Et2O and washed with brine. The organic layer
was dried (MgSO4), filtered and concentrated. The resulting oil was dis-
solved in AcOH/H2O (20 mL, 4:1) and allowed to react for 15 min. The
mixture was concentrated under reduced pressure after which column
J=2.8 Hz, 1H; H-4), 4.78 (s, 1H; H-1’), 4.76 (d, J=11.6 Hz, 1H; CHPh),
4.63 (d, J=11.6 Hz, 1H; CHPh), 4.15 (d, J=8.4 Hz, 1H; H-1), 3.92 (t,
J=10.8 Hz, 1H; H-6’), 3.83 (m, 5H; H-2’, H-3, H-6’, H-4’, H-6), 3.65 (m,
2H; H-6, H-5), 3.52 (m, 5H; H-3’, OMe, H-2), 3.35 (m, 1H; H-5’), 2.80
(brs, 1H; OH), 2.61 (brs, 1H; OH), 2.02 (s, 3H; O(CO)CH3), 1.06 (s,
9H; CH3-tBu) ppm; 13C NMR: d=170.6, 137.3, 135.5, 135.5, 132.8, 129.9,
129.9, 128.7, 128.2, 128.0, 127.8, 102.6, 97.2, 80.2, 76.1, 72.8, 71.9, 66.5,
65.0, 62.4, 61.9, 61.1, 60.7, 57.2, 26.7, 20.7, 19.0 ppm; ESI-HRMS: calcd
for C38H48N6O10Si [M+NH4]: 794.3539; found: 794.3564.
chromatography (ethyl acetate/light petroleum 1:20!1:8) afforded
5
(943 mg, 1.89 mmol, 86% over 2 steps) as a colourless syrup: [a]2D5 ꢀ23.4
Methyl 4-O-acetyl-2-azido-3-O-(2-azido-3-O-benzyl-6-O-tert-butyldime-
thylsilyl-2-deoxy-b-d-mannopyranosyl)-6-O-tert-butyldiphenylsilyl-2-
deoxy-b-l-galactopyranoside (13): TBSCl (101 mg, 0.67 mmol) and
DMAP (15 mg) were added to a solution of diol 12 (471 mg, 0.61 mmol)
in pyridine (10 mL). After stirring for 6 h, MeOH (500 mL) was added
and the volatile compounds were evaporated. Column chromatography
(ethyl acetate/light petroleum 1:10!1:5) furnished 13 (383 mg,
0.44 mmol, 72%) as a colourless oil: [a]2D5 ꢀ38.1 (c=1, CHCl3); IR (thin
(c=1, CHCl3); IR (thin film): n˜ =2980, 2077, 1746, 1381, 1247, 1043 cmꢀ1
;
1H NMR: d=7.64 (m, 4H; H-arom.), 7.37 (m, 6H; H-arom.), 5.43 (d, J=
3.3 Hz, 1H; H-4), 4.19 (d, J=8.0 Hz, 1H; H-1), 3.76 (m, 1H; H-5), 3.70
(m, 3H; H-3, 2ꢃH-6), 3.53 (s, 3H; OMe), 3.47 (dd, J=10.3, 8.0 Hz, 1H;
H-2), 2.96 (brs, 1H; OH), 2.03 (s, 3H; O(CO)CH3), 1.06 (s, 9H; CH3-
tBu) ppm; 13C NMR: d=171.1, 135.3, 132.8, 132.7, 132.5, 132.1, 129.4,
127.6, 102.9, 73.3, 71.2, 68.7, 63.8, 61.3, 56.8, 26.5, 20.5, 18.8 ppm; ESI-
HRMS: calcd for C25H33N3O6Si [M+H]: 500.2211; found: 500.2211.
film): n˜ =2980, 2950, 2071, 1744, 1483, 1356, 1244, 1062 cmꢀ1 1H NMR:
;
Methyl 4-O-acetyl-2-azido-3-O-(2-azido-3-O-benzyl-4,6-O-benzylidene-2-
deoxy-b-d-mannopyranosyl)-6-O-tert-butyldiphenylsilyl-2-deoxy-b-l-gal-
actopyranoside (11b): Tf2O (410 mL, 2.44 mmol) was added dropwise to a
d=7.67 (m, 4H; H-arom.), 7.44 (m, 11H; H-arom.), 5.46 (d, J=2.8 Hz,
1H; H-4), 4.80 (s, 1H; H-1’), 4.77 (d, J=14.6 Hz, 2H; CHPh), 4.74 (d,
J=14.6 Hz, 2H; CHPh), 4.10 (d, J=8.4 Hz, 1H; H-1), 3.91 (m, 2H; 2ꢃ
H-6’), 3.87 (dd, J=10.4, 2.8 Hz, 1H; H-3), 3.85 (t, J=9.6 Hz, 1H; H-4’),
3.75 (m, 2H; H-2’, H-6), 3.67 (t, J=8.0 Hz, 1H; H-6), 3.61 (m, 1H; H-5),
3.53 (m, 5H; H-2, OMe, H-3’), 3.33 (m, 1H; H-5’), 2.95 (s, 1H; OH),
2.04 (s, 3H; O(CO)CH3), 1.05 (s, 9H; CH3-tBu), 0.91 (s, 9H; CH3-tBu),
0.12 (s, 3H; Si-CH3), 0.11 (s, 3H; Si-CH3) ppm; 13C NMR: d=170.3,
137.5, 135.4, 135.4, 132.7, 132.6, 129.8, 129.8, 128.4, 127.9, 127.7, 102.7,
96.5, 80.3, 77.2, 75.8, 75.5, 72.8, 72.1, 68.2, 64.7, 64.0, 61.9, 61.2, 60.8, 57.0,
26.6, 25.7, 20.6, 18.9, 18.1, ꢀ5.6, ꢀ5.6 ppm; ESI-HRMS: calcd for
C44H62N6O10Si2 [M+H]: 891.4139; found: 891.4177.
mixture of
4 (1.14 g, 2.26 mmol), BSP (510 mg, 2.44 mmol), TTBP
(1.12 g; 4.52 mmol) and 3-ꢂ molecular sieves (ꢁ500 mg) in DCM
(50 mL) at ꢀ608C. After stirring at the same temperature for 10 min, 5
(939 mg, 1.88 mmol) in DCM (5 mL) was added dropwise. The mixture
was allowed to warm to RT then Et3N (2 mL) was added. The reaction
mixture was filtered and washed with saturated aqueous NaHCO3,then
the organic layer was dried (MgSO4), filtered and concentrated in vacuo.
The residual oil was purified by column chromatography (light petrole-
um!ethyl acetate/light petroleum 1:10) to give the pure
a isomer
(200 mg, 0.23 mmol, 12%) as a colourless oil and the pure b isomer
(858 mg, 0.99 mmol, 53%) as a white foam: 11a: [a]2D5 +6.2 (c=1,
CHCl3); IR (thin film): n˜ =2985, 2976, 2076, 1746, 1381, 1247, 1076,
Methyl 4-O-acetyl-2-azido-3-O-{2-azido-3-O-benzyl-4-O-(3-O-benzyl-4,6-
O-benzylidene-2-deoxy-2-phthalimido-b-d-glucopyranosyl)-6-O-tert-bu-
tyldimethylsilyl-2-deoxy-b-d-mannopyranosyl}-6-O-tert-butyldiphenylsil-
yl-2-deoxy-b-l-galactopyranoside (2): Tf2O (47 mL, 0.28 mmol) was added
to a mixture of 3 (137 mg, 0.24 mmol), BSP (55 mg, 0.26 mmol), TTBP
(120 mg, 0.48 mmol) and 3-ꢂ molecular sieves (ꢁ200 mg) in dry DCM
(5 mL) at ꢀ608C. After stirring at ꢀ608C for 15 min, 13 (180 mg,
0.20 mmol) in DCM (2 mL) was added. The mixture was allowed to
warm to ꢀ208C over 2 h, after which Et3N (500 mL) was added. The mix-
ture was washed with saturated aqueous NaHCO3 solution and the or-
ganic phases were dried (MgSO4), filtered and evaporated under reduced
pressure to afford a yellow oil which was purified by column chromatog-
raphy (light petroleum!ethyl acetate/light petroleum 1:10) to give trisac-
charide 2 (192 mg, 0.14 mmol, 71%) as a white foam: [a]2D5 ꢀ2.8 (c=1,
1043 cmꢀ1 1H NMR: d=7.61 (m, 4H; H-arom.), 7.38 (m, 16H; H-
;
arom.), 5.60 (s, 1H; CH-benzylidene), 5.40 (d, J=1.6 Hz, 1H; H-4), 5.03
(s, 1H; H-1’), 4.89 (d, J=12.4 Hz, 1H; CHPh), 4.72 (d, J=12.4 Hz, 1H;
CHPh), 4.23 (dd, J=10.2, 4.8 Hz, 1H; H-6’), 4.18 (d, 1H; H-1, 7.6 Hz),
4.10 (t, J=9.2 Hz, 1H; H-4’), 4.00 (m, 3H; H-2’, H-6’, H-3’), 3.81 (m,
2H; H-6, H-3), 3,74 (m, 1H; H-5’), 3.66 (t, J=6.8 Hz, 1H; H-6), 3.62 (m,
1H; H-5), 3.56 (m, 4H; OMe, H-2), 1.93 (s, 3H; O(CO)CH3), 1.05 (s,
9H; CH3-tBu) ppm; 13C NMR: d=169.3, 138.3, 138.1, 135.5, 133.1,
132.85, 129.9, 129.8, 129.4, 128.2, 128.1, 127.8, 127.7, 127.6, 127.5, 103.3,
101.7, 100.8, 78.9, 75.9, 75.0, 73.9, 73.4, 73.3, 68.4, 68.0, 64.6, 63.3, 62.7,
61.5, 57.2, 26.7, 20.5, 19.1 ppm; ESI-HRMS: calcd for C45H52N6O10Si
[M+NH4]: 882.3852; found: 882.3879. 11b: [a]2D5 ꢀ44.2 (c=1, CHCl3); IR
(thin film): n˜ =2986, 2976, 2078, 1746, 1380, 1247, 1074, 1047 ppm;
1H NMR: d=7.63 (m, 4H; H-arom.), 7.39 (m, 16H; H-arom.), 5.63 (s,
1H; CH-benzylidene), 5.48 (d, J=3.2 Hz, 1H; H-4), 4.89 (d, J=12.0 Hz,
1H; CHPh), 4.84 (d, J=1.2 Hz, 1H; H-1’), 4.75 (d, J=12.0 Hz, 1H;
CHPh), 4.34 (dd, J=10.8, 5.2 Hz, 1H; H-6’), 4.16 (d, J=8.0 Hz, 1H; H-
1), 4.02 (t, 1H; H-4’, J=9.6 Hz), 3.92 (m, 2H; H-2’, H-6’), 3.81 (m, 3H;
H-3, H-6, H-3’), 3.69 (t, 1H; H-6, 8.0 Hz), 3.65 (m, 1H; H-5), 3.55 (m,
4H; OMe, H-2), 3.38 (m, 1H; H-5’), 2.10 (s, 3H; O(CO)CH3), 1.05 (s,
9H; CH3-tBu) ppm; 13C NMR: d=170.6, 137.8, 137.2, 135.5, 135.4, 132.8,
132.5, 129.9, 129.8, 129.0, 128.9, 128.4, 128.2, 102.8, 101.5, 97.4, 78.1, 76.5,
75.8, 72.9, 72.8, 68.3, 67.4, 64.8, 63.0, 61.84, 61.1, 57.2, 26.7, 20.7, 19.0;
ESI-HRMS: calcd for C45H52N6O10Si [M+NH4]: 882.3852; found:
882.3867.
CHCl3); IR (thin film): n˜ =2982, 2187, 2114, 1713, 1384, 1080 cmꢀ1
;
1H NMR: d=7.61 (m, 4H), 7.31 (m, 21H; H-arom.), 6.93 (m, 4H; H-
arom.), 5.55 (s, 1H; CH-benzylidene), 5.42 (d, 1H; J=8.4 Hz, H-1’’), 5.36
(d, J=3.2 Hz, 1H; H-4), 4.85 (d, J=12.0 Hz, 1H; CHPh), 4.79 (d, J=
12.0 Hz, 1H; CHPh), 4.73 (d, J=12.0 Hz, 1H; CHPh), 4.64 (s, 1H; H-1’),
4.47 (d, J=12.4, 1H; CHPh), 4.45 (t, J=10.4 Hz, 1H; H-3’’), 4.20 (m,
2H; H-6’’, H-2’’), 4.01 (d, J=8.0 Hz, 1H; H-1), 3.95 (t, J=9.2 Hz, 1H; H-
6’), 3.73 (m, 3H; H-3, H-4’’, H-6’’), 3.65 (d, J=3.1 Hz, 2H; H-2’), 3.59
(m, 6H; H-6, H-3’, H-6, H-6’’, H-5, H-5’’), 3.49 (s, 3H; OMe), 3.44 (dd,
J=10.4, 8.4 Hz 1H; H-2), 3.34 (dd, J=11.6, 5.2 Hz1H; H-4’), 3.07 (m,
1H; H-5’), 1.98 (s, 3H; O(CO)CH3), 1.03 (s, 9H; CH3-tBu), 0.85 (s, 9H;
CH3-tBu), 0.01 (s, 3H; Si-CH3), ꢀ0.03 (s, 3H; Si-CH3) ppm; 13C NMR:
d=170.3 (C=O), 167.6 (C=O), 138.3, 137.9, 137.3 (3ꢃCq-arom.), 135.54,
135.47, 133.9 (3ꢃCH-arom.), 132.8, 132.7, 131.5 (3ꢃCq-arom.), 130.6,
129.9, 129.8, 128.9, 128.7, 128.4, 128.2, 128.0, 127.8, 127.7, 127.5, 127.3,
127.2, 126.2 (14ꢃCH-arom.), 102.8 (C-1), 101.2 (CH-benzylidene), 98.3
(C-1’’), 96.2 (C-1’), 83.0 (C-4’’), 79.0 (C-3’), 76.3 (C-5’), 75.2 (C-3), 74.8
(C-3’’), 74.1 (CH2Ph), 73.2 (C-4’), 72.9 (C-5’’), 72.7 (CH2Ph), 68.7 (C-6’),
65.8 (C-5), 64.5 (C-4), 62.0 (C-2), 62.0 (C-2’), 61.6 (C-6), 61.1 (C-6’), 57.1
(OCH3), 56.6 (C-2’’), 26.7 (CH3-tBu), 26.1 (Cq-tBu), 25.7 (CH3-tBu), 23.9
(Cq-tBu), 20.6 (CH3-acetyl), ꢀ5.5 (Si-CH3), ꢀ5.5 (Si-CH3) ppm; ESI-
HRMS: calcd for C72H85N7O16Si2 [M+Na]: 1382.5484; found: 1382.5481.
Methyl 4-O-acetyl-2-azido-3-O-(2-azido-3-O-benzyl-2-deoxy-b-d-manno-
pyranosyl)-6-O-tert-butyldiphenylsilyl-2-deoxy-b-l-galactopyranoside
(12): Disaccharide 11b (858 mg; 0.99 mmol) was dissolved in MeOH/
THF (30 mL, 2:1) and CSA (30 mg) was added. After 18 h, TLC analysis
(ethyl acetate/light petroleum 1:5) showed full consumption of the start-
ing material had occurred and Et3N (200 mL) was added. Concentration
of the reaction mixture followed by silica gel column chromatography
(ethyl acetate/light petroleum 1:4!1:1) afforded diol 12 (471 mg,
0.61 mmol, 62%) as a white foam: [a]2D5 ꢀ62.0 (c=1, CHCl3); IR (thin
film): n˜ =2978, 2960, 2073, 1748, 1450, 1428, 1371, 1247, 1063 cmꢀ1
;
Methyl 4-O-acetyl-2-azido-3-O-{2-azido-3-O-benzyl-4-O-(2-acetamido-3-
O-benzyl-4,6-O-benzylidene-2-deoxy-b-d-glucopyranosyl)-6-O-tert-butyl-
1H NMR: d=7.62 (m, 4H; H-arom.), 7.39 (m, 11H; H-arom.), 5.45 (d,
1014
ꢁ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2005, 11, 1010 – 1016