SYNTHETIC STUDIES ON SIALOGLYCOCONJUGATES .23. TOTAL SYNTHESIS OF SIALYL-ALPHA(2-]6)-LACTOTETRAOSYLCERAMIDE AND SIALYL-ALPHA(2-]6)-NEOLACTOTETRAOSYLCERAMIDE

The first total syntheses of sialyl-alpha(2 --> 6)-lactotetraosylceramide (29, IV6NeuAcLc4Cer) and sialyl-alpha(2 --> 6)-neolactotetraosylceramide (33, IV6NeuAcnLc4Cer) are described. Methyl O-(methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D glycero-alpha-D-galacto-2-nonulopyranosylonate)-(2 --> 6)-2,4-di-O-benzoyl-3-O benzyl-1-thio-beta-D-galactopyranoside (11), the key glycosyl donor was prepared, via glycosylation of 2-(trimethylsilyl)ethyl 3-O-benzyl-beta-D-galactopyranoside (2) with the methyl alpha-thioglycoside 3 of N-acetylneuraminic acid, benzoylation, replacement of the 2-(trimethylsilyl)ethyl group by acetyl, and introduction of the methylthio group with (methylthio)trimethylsilane. Each coupling of 2-(trimethylsilyl)ethyl O-(2-acetamido-4,6-O-benzylidene-2-deoxy-beta-D-glucopyranosyl)-(1 --> 3')-per-O-benzyl-beta-lactoside side (12) or 2-(trimethylsilyl)ethyl O-(2-acetamido-3-O-acetyl-6-O-benzyl 2-deozy-beta-D-glucopyranosyl)-(1 --> 3')-per-O-benzyl-beta-D-lactoside (14) prepared from 12 by O-acetylation and reductive opening of the benzylidene acetal, with 11 gave the pentasaccharides 16 and 20 in good yields. Compounds 16 and 20-were converted into the corresponding alpha-trichloroacetimidates 19 and 24 which, on coupling with (2S,3R,4E)-2-azido-3-O-benzoyl-4-octadecene-1,3-diol (25), gave the B-glycosides 26 and 30, respectively. Finally, 26 and 30 were transformed, via selective reduction of the azide group, condensation with octadecanoic acid, O-deacylation, and hydrolysis of the methyl ester group, into 29 and 33, respectively.