TOTAL SYNTHESIS OF GANGLIOSIDE GQ1B AND THE RELATED POLYSIALOGANGLIOSIDES

被引:20
作者
ISHIDA, HK
ISHIDA, H
KISO, M
HASEGAWA, A
机构
[1] Department of Bioorganic Chemistry, Gifu University, Gifu
关键词
D O I
10.1016/S0957-4166(00)80396-1
中图分类号
O61 [无机化学];
学科分类号
070301 ; 081704 ;
摘要
The first total synthesis of ganglio-series gangliosides GQ1b, GT1b and GD1b, which contain alpha-sialyl-(2-->8)-alpha-sialic acid residue in the structure, will be described. Glycosylation of 2-(trimethyl silyl)ethyl O-(2-acetamido-6-O-benzyl-2-deoxy-3,4-O-isopropylidene-beta-D-galactopyranosyl)- (1-->4)-O-(2,6-di-O-benzyl-beta-D-galactopyranosyl)-(1-->4)-2,3,6-tri-O-benzyl-beta-D-glucopyranoside (7) with methyl [phenyl 5-acetamido-8-O-(5-acetamido-4,7,8,9-tetra-O-acetyl-3,5 -dideoxy-D-glycero-alpha-D-galacto-2-nonulopyranosylono- 1',9-lactone)-4,7-di-O-acetyl-3,5-dideoxy-2-thio-D-glycero -D-galacto-2-nonulopyranosid]onate (8) using N-iodosuccinimide (NIS)-trifluoromethanesulfonic acid (TfOH) in acetonitrile gave the protected GD2 pentasaccharide 9, which was converted into the pentasaccharide acceptor 10 by de-O-isopropylidenation. Glycosylation of 10 with methyl thioglycoside derivatives 18, 26, 34 by use of dimethyl(methyl thio)sulfonium triflate (DMTST) gave the protected ganglioside oligosaccharides 19, 27 and 35, respectively. Compounds 9, 19, 27 and 35 were transformed into the corresponding alpha-trichloroacetimidates 13, 22, 30 and 38, via reductive removal of benzyl groups, O-acetylation, selective removal of 2-(trimethylsilyl)ethyl group, and treatment of trichloroacetonitrile. Condensation of the imidates 13, 22, 30 and 38 with (2S,3R,4E)-2-azido-3-O-benzoyl-4-octadecene-1,3-diol (14) gave the corresponding beta-glycosides 15, 23, 31 and 39, which were converted, via selective reduction of azido group, coupling with octadecanoic acid, de-O-acylation, and saponification of methyl esters and lactone groups, into the corresponding gangliosides GD2 (17), GD1b (25), GT1b (33) and GQ1b (41).
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页码:2493 / 2512
页数:20
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