SYNTHETIC STUDIES ON SIALOGLYCOCONJUGATES .61. - SYNTHESIS OF ALPHA-SERIES GANGLIOSIDE GM1-ALPHA

A stereocontrolled synthesis of alpha-series ganglioside GM1 alpha (III(6)Neu5AcGgOse(4)Cer) is described. Glycosylation of 2-(trimethylsilyl)ethyl O-(2,3,6-tri-O-benzyl-beta-D-galactopyranosyl)-(1-->4)-2,3,6-tri-O-benzyl-beta-D-glucopyranoside (1) with the suitably protected galactosamine donor, methyl 3-O-acetyl-4,6-O-benzylidene-2-deoxy-2-phthalimido-1-thio-beta-D-galactopyranoside (4) gave the desired trisaccharide, which was transformed into the trisaccharide acceptor via removal of the phthaloyl and O-acetyl groups followed by N-acetylation. Glycosylation of this acceptor with methyl 3-O-benzyl-2,4,6-tri-O-benzoyl-1-thio-beta-D-galactopyranoside (7) gave the asialo GM1 saccharide derivative, which was transformed into the acceptor by removal of benzylidene group. Coupling of this gangliotetraose acceptor with phenyl (methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-2-thio-D-glycero-D-galacto-2-noulopyranosyl)onate by use of NIS-TfOH afforded the desired GM1 alpha oligosaccharide derivative in high yield, which was transformed, via removal of the benzyl group followed by O-acetylation, selective removal of the 2-(trimethylsilyl)ethyl group and subsequent imidate formation, into the final glycosyl donor. Condensation of this imidate derivative with (2S,3R,4E)-2-azido-3-O-benzoyl-4-octadecene-1,3-diol (15) gave the beta-glycoside, which on channeling through selective reduction of azido group, coupling of the amino group with octadecanoic acid, O-deacylation and saponification of the methyl ester group, gave the tide compound GM1 alpha.