Synthesis of 1,2- and 1,3-N-Linked Disaccharides of 5-Thio-α-d-mannopyranose as Potential Inhibitors of the Processing Mannosidase Class I and Mannosidase II Enzymes

The syntheses of S/N acetal heteroatom analogues of 1,2- and 1,3-linked mannopyranose disaccharides are described. The compounds are analogues of the Man-α-(1→2)-Man and Man-α-(1→3)-Man disaccharide components of oligosaccharides found in N-glycoproteins that are cleaved by trimming mannosidases during glycoprotein processing. Glycosylamine formation, without the necessity of hydroxyl group protection, proceeded through acid-catalyzed condensation reactions of 5-thio-d-mannose with either methyl 2-amino-2-deoxy- or 3-amino-3-deoxy-α-d-mannopyranoside to give methyl 2-amino-2-deoxy-2-N-(5-thio-α/β-d-mannopyranosyl)-α-d-mannopyranoside (2) or methyl 3-amino-3-deoxy-3-N-(5-thio-α/β-d-mannopyranosyl)-α-d-mannopyranoside (3), respectively. The superiority of mercuric chloride over acetic acid as a catalyst for this reaction is reported. Acetylation of the anomeric mixtures gave the heptaacetates from which the major β‘-isomers could be separated by chromatography and/or crystallization.