Synthetic Studies on Sialoglycoconjugates. 5: A Facile, Regio and Stereoselective Synthesis of Ganglioside GM4and Its Position Isomer1

Abstract

Ganglioside GM₄ and its positional isomer have been synthesized. 2-(Trimethylsilyl)ethyl 6-O-benzoyl-β-D-galactopyranoside (4) was prepared from 2-(trimethylsilyl)ethyl β-D-galactopyranoside (1) by selective 3-O-benzylation, 6-O-benzoylation and subsequent removal of the benzyl group, or by 3,4-O-isopropylidenation, 6-O-benzoylation and O-deisopropylidenation. 2-(Trimethylsilyl)ethyl 3-O-benzoyl-β-D-galactopyranoside (5) was obtained by selective benzoylation of 1. The glycosidation of 4 or 5 with the methyl α-thioglycoside derivative (9), derived from methyl 5-acetamido-4,7,8,9-tetra-0-acetyl-2-S-acetyl-3,5-dTdeoxy-2-thio-D-glycero-a-D-galacto-2-nonulopyranosonate (8) via selective S-deacetylation and subsequent S-methylation, using dimethyl(methylthio)sulfonium triflate (DMTST) gave the corresponding α-glycosides (10, 12) of Neu5Ac, respectively. Coupling of the trichloroacetimidates (15, 17), obtained from 10 and 12 by O-acetylation, selective removal of the 2-(trimethylsilyl)ethyl group, and imidate formation, with (2S, 3R, 4E)-2-azido-3-O-benzoyl-4-octadecene-1,3-diol (18) gave the corresponding β-glycosides (19, 25), which were converted via selective reduction of the azide group, condensation with fatty acids, O-deacylation, and hydrolysis of the methyl ester group into the title compounds.