SYNTHETIC STUDIES ON SIALOGLYCOCONJUGATES-91 - TOTAL SYNTHESIS OF GANGLIOSIDES GD1C AND GT1A

A first total synthesis of gangliosides GD1c and GT1a containing Neu5A c alpha(2-->8) Neu5Ac alpha(2-->3)Gal residue in their non-reducing te rminal is described. Condensation of methyl O-[methyl ctone)-4,7-di-O- acetyl-3,5-dideoxy-D-glycero-alpha onulopyranosylonate]-(2-->3)-2,4,6- tri-O-benzoyl-1 -thio-beta-D-galactopyranoside (1) with 2-(trimethylsi lyl)ethyl O-(2-acetamido-4,6-O-benzylidene-2-deoxy-beta-D actopyranosl )-(1-->4)-O-(2,3,6-tri-O-benzyl-beta-D -galactopyranosyl)-(1-->4)-2,3, 6-tri-O-benzyl-beta-D-glucopyranoside (2) or 2-(trimethylsilyl)ethyl O-(2-acetamido-6-O-benzyl-2 -deoxy-beta-D-galactopyranosyl)-(1-->4)-O- [methyl amido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D-glycero -alpha-D-ga lacto-2-nonulopyranosylonate)-(2-->3) -(2,6-di-O-benzyl-beta-D-galacto pyranosyl)-(1-->4) -2,3,6-tri-O-benzyl-beta-D-glucopyranoside (3) in t he presence of dimethyl(methylthio)sulfonium triflate (DMTST) gave the corresponding hexa- and heptasaccharide derivatives 4 and 5, respecti vely. These oligosaccharides were converted into the alpha-trichloroac etimidates 10 and 11 via reductive removal of the benzyl groups and/or benzylidene group, O-acetylation, selective removal of the 2-(trimeth ylsilyl)ethyl group and treatment with trichloroacetonitrile, which, o n coupling with 2-azidosphingosine derivatives 12 or 13, gave the beta -glycosides 14 and 15, respectively. Finally, 14 and 15 were transform ed, via selective reduction of the azido group, coupling with octadeca noic acid and removal of all protecting groups, into the title ganglio sides GD1c 18 and GT1a 19.