SYNTHETIC STUDIES ON SIALOGLYCOCONJUGATES .28. SYNTHESIS OF A POSITION ISOMER OF GANGLIOSIDE GD3 HAVING AN ALPHA-NEU5AC-(2-]9)-ALPHA-NEU5AC LINKAGE

A position isomer of ganglioside GD3 has been synthesized in which N-acetylneuraminic acid (Neu5Ac) is linked alpha-glycosidically at C-9 of the Neu5Ac residue of the ganglioside GM3 structure. The coupling of 2-(trimethylsilyl)ethyl O-(6-O-benzoyl-beta-D-galactopyranosyl)-(1 --> 4)-2,6-di-O-benzoyl-beta-D-glucopyranoside with methyl O-(methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D-glycero-alpha-D-galacto-2-nonulopyranosylonate)-(2 --> 9)-(methyl 5-acetamido-4,7,8-tri-O-acetyl-3,5-dideoxy-2-thio-D-glycero-D-galacto-2-nonulopyranosid)onate, prepared from the corresponding 2-(trimethylsilyl)ethyl glycoside by selective removal of the 2-(trimethylsilyl)ethyl group, 1-O-acetylation, and introduction of the methylthio group with trimethyl(methylthio)silane, using N-iodosuccinimide-trifluoromethanesulfonic acid as a glycosylation catalyst, gave a tetrasaccharide (5). Compound 5 was converted, via O-acetylation, selective removal of the 2-(trimethylsilyl)ethyl group, and subsequent imidate formation, into a protected alpha-Neu5Ac-(2 --> 9)-alpha-Neu5Ac-(2 --> 3')-alpha-lactosyl trichloroacetimidate (8). Glycosylation of (2S,3R,4E)-2-azido-3-O-benzoyl-4-octadecene-1,3-diol with 8 afforded a ceramide precursor which was transformed, via selective reduction of the azido group, coupling with octadecanoic acid, O-deacylation, and hydrolysis of the methyl ester groups, into to the title ganglioside.