Synthetic Studies on Sialoglycoconjugates 71: Synthesis of Sulfo- and Sialyl-Lewis × Epitope Analogs Containing the 1-Deoxy-N-acetylgulcosamine in Place of N-Acetylglucosamine Residue

Abstract

Sulfo and sialy Le^x epitope analogs containing the 1-deoxy-N-acetylglucosamine in place of GlcNAc residue have been synthesized. Glycosylation of 2-acetamido-1,5-anhydro-3,6-di-O-benzyl-2-deoxy-D-glucitol (10) with 2,4,6-tri-O-benzoyl-3-O-levulinyl-α-D-galactopyranosyl trichloroacetimidate (6) prepared from 2-(trimethylsilyl)ethyl β-D-galactopyranoside (1) in five steps, or with the α-sialyl-(2→3)-galactose donor, afforded the dessired β-glycosides 12 and 15, respectively. Glycosylation of the acceptor 14 derived from 12 in two steps, or 16 derived from 15 by reductive removal of the benzyl group followed by selective O-benzoylation, with methyl 2,3,4-tri-O-benzyl-1-thio-β-fucopyranoside (17), using dimethyl(methylthio)sulfonium triflate, gave the trisaccharide 18 and tetrasaccharide 23. Compound 18 was converted via reductive removel of the benzyl groups, O-acetylation, selective removel of the levulinyl group, treatment with sulfur trioxidepyridine complex, and O-deacylation, into the title sulfo Le^x analog 22. Compound 23 was transformed by reductive removal of the benzyl groups, O-acetylation, O-deacylation and subsequent hydrolysis of the methyl ester, into the sLe^x epitope analog 25.