Synthesis of a thio analogue of n-propyl kojibioside, a potential glucosidase inhibitor

The disaccharide α-d-Glcp-(1-S-2)-β-d-Glcp-(1-OPr) 1, a thio analogue of α-d-Glcp-(1 → 2)-α-d-Glcp-(1-OPr)(n-propyl kojibioside) in which the inter-glycosidic oxygen atom is replaced by sulfur, has been synthesized for evaluation as a potential glucosidase inhibitor. Glycosylation of the 2-thiol glucopyranosyl acceptor 4 with the trichloroacetimidate of 2,3,4,6-tetra-O-benzyl-α-d-glucopyranose 5 gave the α-linked disaccharide 6 stereoselectively. Deprotection was performed by hydrogenolysis in the presence of Pd/C to give 1 as the β-n-propyl glycoside. Glycosylation of the thiol 4 with the trichloroacetimidate of 2,3,4,6-tetra-O-acetyl-α-d-glucopyranose 8 gave a 1:2.3 mixture of the α and β disaccharides (9 and 10); evidence is presented for the occurrence of the orthoester 11, as an intermediate in the formation of the β-disaccharide.