SYNTHETIC STUDIES ON SIALYLGLYCOCONJUGATES .13. STEREOSELECTIVE SYNTHESIS OF SIALYL-LACTOTETRAOSYLCERAMIDE AND SIALYLNEOLACTOTETRAOSYLCERAMIDE

The first total syntheses of sialyl-lactotetraosylceramide (28, IV3NeuAcLc4Cer) and sialylneolactotetraosylceramide (32, IV3NeuAcnLc4Cer) are described. Methyl O-(methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-d-glycero-α-d- galacto-2-nonulopyranosylonate)-(2→3)-2,4,6-tri-O-benzoyl-1-thio-β-d-galactopyranoside (4), the key glycosyl donor, was prepared from 2-(trimethylsilyl)ethyl O-(methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-d- glycero-α-d-galacto-2-nonulopyranosylonate)-(2→3)-6-O-benzoyl- β-d-galactopyranoside (1), via benzoylation, replacement of the 2-(trimethylsilyl)ethyl group by acetyl, and introduction of the methylthio group with methylthiotrimethylsilane. Coupling of 2-(trimethylsilyl) ethyl 2,3,6,2′,4′,6′-hexa-O-benzyl-β-d-lactoside (8), prepared from 2-(trimethylsilyl)ethyl β-d-lactoside (5) via selective 3′-O-(4-methoxybenzylation), benzylation, and selective removal of the 4-methoxybenzyl group, with 3,4,6-tri-O-acetyl-2-deoxy-2-phthalimido-d-glucopyranosyl bromide (9) gave a trisaccharide derivative 10, from which the phthaloyl and O-acetyl groups were removed. N-Acetylation then gave 2-(tri-methylsilyl)ethyl O-(2-acetamido-2-deoxy-β-d-glucopyranosyl)-(1→3)-O-(2,4,6-tri-O-benzyl-β-d-galactopyranosyl)-(1→4)-2,3,6-tri-O- benzyl-β-d-glucopyranoside (12). Dimethyl(methylthio)sulfonium triflatepromoted coupling of 4 with 13, prepared from 12 by 4,6-O-benzylidenation, or with 15, obtained from 13 by O-(4-methoxybenzylation) and reductive opening of the benzylidene acetal, gave the corresponding pentasaccharide derivatives 16 and 20 in good yields. Compounds 16 and 20 were converted into the corresponding α-trichloroacetimidates 19 and 23 which, on coupling with (2S,3R,4E)-2-azido-3-O-benzoyl-4-octadecene-1,3-diol (24), gave the β-glycosides 25 and 29, respectively. Finally, 25 and 29 were transformed, via selective reduction of the azide group, condensation with octadecanoic acid, O-deacylation, and hydrolysis of the methyl ester group, into 28 and 32, respectively. © 1990.