Synthesis of α- and β-linked tyvelose epitopes of the Trichinella spiralis glycan: 2-Acetamido-2-deoxy-3-O-(3,6-dideoxy-D- arabinohexopyranosyl)-β-D-galactopyranosides

Article abstract of DOI:10.1016/S0008-6215(96)00229-7

The anomeric configuration of tyvelose, 3,6-dideoxy-D-arabino-hexopyranose, in the recently discovered glycan epitopes of the parasite Trichinella spiralis has not been established. Two 2-(trimethylsilyl)ethyl disaccharide glycosides, α- and β-Tyv-(1 → 3)-β-D-GalNAc (4 and 5) have been synthesized to provide model compounds that, together with the methyl 3,6-dideoxy-α-and β-D-arabino-hexopyranosides (2 and 3), aid the determination of the anomeric configuration of tyvelose residues in the parasite glycan, either indirectly by immunochemical inhibition data or directly by the technique of ¹H NMR spectroscopy. Methyl 3,6-dideoxy-β-D-arabinohexopyranoside (3) was synthesized from methyl 2,3-anhydro-4,6-O-benzylidene-β-D- mannopyranoside (9) by a method previously used for the α anomer 2. Benzylation of 2 provided a route to the glycosyl donor, 2,4-di-O-benzyl-3,6-dideoxy-α- D-arabino -hexopyranosyl chloride (30), that reacted with the selectively protected 2-acetamido-2-deoxy-D-galactopyranoside alcohol 18 in the presence of an insoluble silver zeolite catalyst to give the α- and β-linked disaccharides 31 and 32. Glycosylation of the related 2-acetamido-2-deoxy-D-galactopyranoside alcohol 27 by 30 under similar conditions provided disaccharides 33 and 34 containing a tether. Deprotection of the saccharide and derivatization of the tether with 1,2-diaminoethane provided amide derivatives 35 and 36 suitable for the preparation of neoglycoconjugate antigens. Complete ¹H and ¹3C NMR chemical shifts of the deprotected disaccharides and monosaccharides are reported.