Synthesis of heteroanalogues of disaccharides as potential inhibitors of the processing mannosidase Class I enzymes

Abstract

Three disaccharide analogues of α- d-Man-(1→2)- α- d-Man-OMe in which the ring and/or glycosidic oxygen atoms have been replaced by sulfur have been synthesized as potential inhibitors of Class I mannosidase enzymes. Glycosylation of appropriately protected methyl α- d-mannopyranosides, having free alcohol or thiol functional groups at the 2-position, with 2,3,4,6-tetra- O-acetyl-5-thio- α- d-mannopyranosyl trichloroacetimidate was selective for the synthesis of α-linked disaccharides in the case of the 2-alcohols, but yielded an α/ β mixture in the case of the 2-thiol glycosyl acceptors. A disaccharide containing a single sulfur in the linkage was synthesized by nucleophilic substitution of the 2-triflate of a methyl α- d-glucopyranoside derivative by the thiolate anion of 2,3,4,6-tetra- O-acetyl-1-thio- α- d-mannopyranose. Protecting groups were removed by standard methods to give the free heterosubstituted disaccharides.