SYNTHETIC STUDIES ON SIALOGLYCOCONJUGATES .40. STEREOCONTROLLED SYNTHESIS OF SIALYL LEWIS-X EPITOPE AND ITS CERAMIDE DERIVATIVE

Stereocontrolled synthesis of sialyl Le(x) epitope and its ceramide derivative with regard to the introduction of galactose or beta-D-galactosyl ceramide into the terminal N-acetylglucosamine residue of sialyl Le(x) determinant is described. Konigs-Knorr condensation of 2-(trimethylsilyl)ethyl 2,4,6-tri-O-benzyl-beta-D-galactopyranoside (4) with 3,4,6-tri-O-acetyl-2-deoxy-2-phthalimido-D-glucopyranosyl bromide (5) gave the desired beta-glycoside 6, which was converted into 2-(trimethylsilyl)ethyl O-(2-acetamido-4,6-O-benzylidene-2-deoxy-beta-D-glucopyranosyl)-(1-->3)-2,4,6-tri-O-benzyl-beta-D-galactopyranoside (8) via removal of the phthaloyl and O-acetyl groups, followed by N-acetylation and 4,6-O-benzylidenation. Glycosylation of 8 with methyl 2,3,4-tri-O-benzyl-1-thio-beta-L-fucopyranoside (9) gave the alpha-glycoside (10), which was transformed by reductive ring-opening of the benzylidene acetal into the acceptor (11). Dimethyl(methylthio)sulfonium triflate (DMTST)-promoted coupling of 11 with methyl O-(methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D-glycero-alpha-D galacto-2-nonulopyranosylonate)-(2-->3)-2,4,6-tri-O-benzoyl-1-thio-beta-D-galactopyranoside (12) afforded the desired pentasaccharide (13), which was converted into the alpha-trichloroacetimidate 16 via reductive removal of the benzyl groups, then O-acetylation, removal of the 2-(trimethylsilyl)ethyl group and treatment with trichloroacetonitrile. Condensation of 16 with (2S,3R,4E)-2-azido-3-O-benzoyl-4-octadecene-1,3-diol (18) gave the beta-glycoside 19, which was transformed into the title compound 21, via reduction of the azido group, coupling with octadecanoic acid, O-deacylation and hydrolysis of the methyl ester group. On the other hand, O-deacylation of 13 and subsequent hydrolysis of the methyl ester group gave the pentasaccharide epitope 17.