Methyl 3,4,6-tri-O-acetyl-2-(2,2,2-trichloroethoxycarbonyl-
amino)-2-deoxy-1-thio-ꢁ-D-galactopyranose 8
J 7.6 and 10.6, H-2Ј), 5.42 (1H, br d, J 3.2, H-4ٞ), 5.37 (1H, dd,
J 7.9 and 9.2, H-2), 5.17 (1H, t, J 3.1, H-3Ј), 5.14 (1H, t, J 3.3,
H-3ٞ), 5.04 (1H, d, J 7.7, H-1Ј), 4.91 (1H, d, J 8.4, H-1ٞ), 4.67
(1H, d, J 7.7, H-1), 4.64 (1H, d, J 3.4, H-1Љ), 4.55 (1H, dd, J 4.1,
6.3, H-2ٞ), 4.32 (1H, m, H-2Љ), 3.70 (2H, m, OCH2CH2), 3.33
(3H, m, CH2Br, H-5Ј), 2.20, 2.15, 2.00, 1.87 (3H each, 4 s, Ac);
m/z 1856.5060 (Mϩ ϩ Na. C97H96BrNNaNO30 requires m/z,
1856.5098).
To a mixture of 1,3,4,6-tetra-O-acetyl-2-(2,2,2-trichloroethoxy-
carbonylamino)-2-deoxy-α/β--galactopyranose45,56 7 (α/β 1 : 3;
47.7 g, 91.0 mmol), trimethyl(methylthio)silane (16.7 g, 140
mmol) and MS AW-300 (activated, 10 g) in 1,2-dichloroethane
(400 mL) was added trimethylsilyl trifluoromethanesulfonate
(20 g, 91.0 mmol). The mixture was filtered after two days,
diluted with dichloromethane, washed with saturated aq.
sodium hydrogen carbonate, dried (Na2SO4), filtered and con-
centrated. Flash chromatography (SiO2; heptane–EtOAc 2 : 1 to
1 : 1 gradient) gave 8 (44.6 g, 96%); [α]D25 Ϫ18 (c 1 in CHCl3); δH
(400 MHz; CDCl3) 5.42 (1H, dd, J 0.7 and 3.2, H-4), 5.13 (1H,
dd, J 3.2 and 10.9, H-3), 5.03 (1H, d, J 9.6, NH), 4.82 (1H, d,
J 12.0, CH2CCl3), 4.69 (1H, d, J 12.0, CH2CCl3), 4.53 (1H, d,
J 10.3, H-1), 4.18 (1H, dd, J 6.8 and 11.3, H-6), 4.14 (1H, dd,
J 6.6 and 11.3, H-6), 4.04 (1H, br q, J 10.2, H-2), 3.96 (1H, dt,
J 0.9 and 6.7, H-5), 2.25 (3 H, s, SCH3), 2.18, 2.05, 2.01 (3 H
each, 3 s, Ac); m/z 531.9987 (Mϩ ϩ Na. C16H22Cl3NNaO9S
requires m/z, 531.9979).
2-Bromoethyl 4-O-{4-O-[3-O-(2-acetamido-2-deoxy-ꢁ-D-
galactopyranosyl)-ꢀ-D-galactopyranosyl]-ꢁ-D-galacto-
pyranosyl}-ꢁ-D-glucopyranoside 13
A solution of compound 12 (100 mg, 54 µmol) in AcOH (4 mL)
was hydrogenolysed over 10% Pd–C (40 mg) for 24 h, filtered
and concentrated. The residue was treated with methanolic
sodium methoxide (0.09 M; 2.5 mL) at room temperature for
16 h. The solution was neutralized with Duolite C436 (Hϩ)
resin, filtered and concentrated. Column chromatography
(SiO2, CH2Cl2–MeOH–H2O 10 : 5 : 1) gave 13 (35 mg, 79%); [α]D25
ϩ15 (c 0.2 in H2O); δH (400 MHz; D2O) 4.79 (1H, d, J 3.9,
H-1Љ), 4.51 (1H, d, J 8.4, H-1ٞ), 4.44 (1H, d, J 8.0, H-1), 4.39
(1H, d, J 7.7, H-1Ј), 4.25 (1H, br t, J 6.7, H-5Љ), 4.13 (1H, br d,
J 2.7, H-4Љ), 3.46 (1H, dd, J 7.8 and 10.3, H-2Ј), 3.23 (1H, dd,
J 8.1 and 9.0, H-2), 1.92 (3H, s, Ac); m/z 836.1831 (Mϩ ϩ Na.
C28H48BrNNaO21 requires m/z, 836.1800).
2-Bromoethyl 2,3,6-tri-O-benzoyl-4-O-{2,3,6-tri-O-benzoyl-4-O-
[2,4,6-tri-O-benzyl-3-O-(3,4,6-tri-O-acetyl-2-(2,2,2-trichloro-
ethoxycarbonylamino)-2-deoxy-ꢁ-D-galactopyranosyl)-ꢀ-D-
galactopyranosyl]-ꢁ-D-galactopyranosyl}-ꢁ-D-glucopyranoside 11
To a solution of 5 (2.27 g, 2.11 mmol) and 6 (2.10 g, 3.17 mmol)
in CH2Cl2–Et2O (1 : 2; 66 mL) was added MS AW-300 (acti-
vated, 1 g) and the mixture was stirred under N2 for 4 h. The
mixture was then cooled to Ϫ45 ЊC and NIS (922 mg, 4.13
mmol) and TfOH (50 µL, 0.2 eq.) were added. After 40 min,
TLC showed the complete disappearance of the donor 6 and
formation of the desired product 9. To the mixture was then
added TfOH (50 µL), the temperature was raised to 0 ЊC and
the mixture was stirred for 40 min. The temperature of the
reaction mixture was again lowered to Ϫ45 ЊC and the donor 8
(1.20 g, 2.34 mmol) and NIS (600 mg, 2.67 mmol) were added.
After 30 min, the reaction mixture was diluted with dichloro-
methane, filtered through Celite, washed successively with 10%
aq. Na2S2O3 and 1 M aq. NaHCO3, dried (Na2SO4) and con-
centrated. Column chromatography (SiO2; toluene–EtOAc,
12 : 1 to 6:1 gradient) gave 11 (3.2 g, 76%); [α]D25 ϩ39 (c 1 in
CHCl3); δH (400 MHz; CDCl3) 5.88 (1H, t, J 9.3, H-3), 5.73
(2H, dd, J 7.7 and 10.5, H-2Ј and NH), 5.47 (1H, br d, J 2.8,
H-4ٞ), 5.37 (1H, dd, J 7.9 and 9.3, H-2), 5.16 (1H, dd, J 3.0 and
7.8, H-3ٞ), 5.13 (1H, dd, J 2.7 and 10.4, H-3Ј), 5.05 (1H, d,
J 7.7, H-1ٞ), 4.94 (1H, d, J 8.3, H-1Ј), 4.67 (1H, d, J 7.9, H-1),
4.32 (1H, t, J 9.6, H-4), 4.25 (3H, m, H-2ٞ and OCH2CH2), 3.95
(1H, dd, J 3.0 and 10.5, H-2Љ), 3.32 (2H, m, CH2Br), 2.90 (1H,
dd, J 5.8 and 8.2, H-6Љ), 2.15, 2.01, 2.00 (3H each, 3 s, Ac);
m/z 1988.4076 (Mϩ ϩ Na. C98H95BrCl3NaO31 requires m/z,
1988.4035).
2-Bromoethyl 2,3,6-tri-O-acetyl-4-O-{2,3,6-tri-O-acetyl-4-O-
[2,4,6-tri-O-acetyl-3-O-(2-acetamido-3,4,6-tri-O-acetyl-2-
deoxy-ꢁ-D-galactopyranosyl)-ꢀ-D-galactopyranosyl]-ꢁ-D-
galactopyranosyl}-ꢁ-D-glucopyranoside 14
Compound 13 (35 mg, 43 µmol) was acetylated with Ac2O (0.2
mL), pyridine (0.4 mL) and 4-(dimethylamino)pyridine
(DMAP) (10 mg) for 16 h. Concentration and column chrom-
atography of the residue (SiO2; EtOAc) gave 14 (50 mg, 88%);
[α]D25 ϩ44 (c 0.5 in CHCl3); δH (400 MHz; CDCl3) 5.65 (1H, d,
J 8.7, NH), 5.60 (1H, br d, J 2.9, H-4Љ), 5.35 (1H, br d, J 3.2,
H-4ٞ), 5.27 (1H, dd, J 3.2 and 11.2, H-3ٞ), 5.23 (1H, t, J 9.2,
H-3), 5.20 (1H, dd, J 3.5 and 10.6, H-2Љ), 5.13 (1H, dd, J 7.6
and 10.8, H-2Ј), 4.96 (1H, d, J 3.5, H-1Љ), 4.92 (1H, dd, J 8.0
and 9.3, H-2), 4.85 (1H, d, J 8.2, H-1ٞ), 4.76 (1H, dd, J 2.4 and
10.9, H-3Ј), 4.56 (1H, d, J 7.6, H-1Ј), 4.55 (1H, d, J 7.9, H-1),
4.20 (1H, dd, J 3.3 and 10.9, H-3Љ), 3.91 (1H, dt, J 8.7 and 11.0,
H-2ٞ), 3.45 (2H, m, CH2Br), 2.14, 2.13, 2.12, 2.10, 2.09, 2.07,
2.06, 2.05, 1.99, 1.92 (39 H, 10 s, Ac); m/z 1340.3063 (Mϩ ϩ Na.
C52H72BrNNaO33 requires m/z, 1340.3068).
Acknowledgements
This work is dedicated to the memory of Professor Göran
Magnusson. We will remember Göran as a close friend and as a
supportive and enthusiastic mentor and colleague.
Financial support by the Swedish Natural Science Research
Council and Lundonia Biotech is acknowledged.
2-Bromoethyl 2,3,6-tri-O-benzoyl-4-O-{2,3,6-tri-O-benzoyl-4-O-
[2,4,6-tri-O-benzyl-3-O-(2-acetamido-3,4,6-tri-O-acetyl-2-
deoxy-ꢁ-D-galactopyranosyl)-ꢀ-D-galactopyranosyl]-
ꢁ-D-galactopyranosyl}-ꢁ-D-glucopyranoside 12
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