SYNTHESIS OF HETEROANALOGUES OF DISACCHARIDES AS POTENTIAL INHIBITORSOF THE PROCESSING MANNOSIDASE CLASS-I ENZYMES

Three disaccharide analogues of alpha-D -Man-(l-->2)-alpha-D-Man-OMe i n which the ring and/or glycosidic oxygen atoms have been replaced by sulfur have been synthesized as potential inhibitors of Class I mannos idase enzymes. Glycosylation of appropriately protected methyl alpha-D -mannopyranosides, having free alcohol or thiol functional groups at t he 2-position, with 3,4,6-tetra-O-acetyl-5-thio-alpha-D-mannopyranosyl trichloroacetitmidate was selective for the synthesis of cr-linked di saccharides in the case of the 2-alcohols, but yielded an alpha/beta m ixture in the case of the 2-thiol glycosyl accepters. A disaccharide c ontaining a single sulfur in the linkage was synthesized by nucleophil ic substitution of the 2-triflate of a methyl alpha-D-glucopyranoside derivative by the thiolate anion of 3,4,6-tetra-O-acetyl-1-thio-alpha- D-mannopyranose. Protecting groups were removed by standard methods to give the free heterosubstituted disaccharides. (C) 1998 Elsevier Scie nce Ltd. All rights reserved.