SYNTHETIC STUDIES ON SIALOGLYCOCONJUGATES .73. SYNTHESIS OF KDN-ALPHA-(2-]6)-LACTOTETRAOSYLCERAMIDE AND KDN-ALPHA-(2-]6)-NEOLACTOTETRAOSYLCERAMIDE

Analogs of sialyl-alpha(2 --> 6)-lactotetraosylceramide and sialyl-alpha(2 --> 6)-neolactotetraosylceramide, in which the N-acetylneuraminic acid residue is replaced by a 3-deoxy-D-glycero-D-galacto-2-nonulopyranosylonic acid (KDN) unit, have been synthesized. Methyl O-(methyl 4,5,7,8,9-penta-O-acetyl-3-deoxy-D-glycero-alpha-D- galacto-2-nonulopyranosylonate)-(2 --> 6)-2,4-di-O-benzoyl-3-O-benzyl-1-thio-beta-D-galactopyranoside (6) was prepared from the phenyl beta-thioglycoside derivative 1 of KDN and 2-(trimethylsilyl)ethyl 3-O-benzyl-beta-D-galactopyranoside (2) in four steps. 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 (7) or 2-(trimeth)lsilyl)ethyl O-(2-acetamido-3,6-di- O-benzyl-2-deoxy-beta-D-glucopyranosyl)-(1 --> 3')-per-O-benzyl-beta-D-lactoside (8), with 6 gave the pentasaccharides 9 and 13 in good yields. Compounds 9 and 13 were converted into the corresponding alpha-trichloroacetimidates 12 and 16 which on glycosylation with (2S,3R,4E)-2-azido-3-O-benzoyl-4-octadecene 1,3-diol (17), gave the beta-glycosides 18 and 21, respectively. Finally, 18 and 21 were transformed, via selective reduction of the azido group, condensation with octadecanoic acid, O-deacylation, and saponification of the methyl ester group, into the target compounds 20 and 23, respectively.