Synthesis of α- and β-linked tyvelose epitopes of the Trichinella spiralis glycan: 2-acetamido-2-deoxy-3-O-(3,6-dideoxy-d-arabino-hexopyranosyl)-β-d-galactopyranosides

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-arabino-hexopyranoside (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.