Synthesis of disaccharides, containing sulfur in the ring of the reducing monosaccharide unit, through a nonglycosylating chemical strategy

The synthesis of disaccharides containing sulfur in the reducing ring throu gh a nonglycosylating chemical strategy is described. Lactose, maltose and cellobiose were transformed in several steps into the appropriately protect ed 4-O-glycosyl-2,3-O-isopropyliden-nldehydo-D-glucose dimethyl acetals (6, 11: 18 and 27) and 4-O-glycosyl-2,3-O-isopropyliden-aldehydo-L-idose dimet hyl acetals (42a and 42b), Compounds 6, 1L 18 and 27 were converted into th e corresponding 4-O-glycosyl-5,6-dideoxy-5,6-epithio-2,3-O-isopropylidene-a lde- hydo-L-idose dimethyl acetals 33e-h via the 5,6-cyclic sulfates 31a-d, by reaction with potassium thioacetate or potassium thiocyanate and treatm ent with NaOMe/MeOH. Nucleophilic ring opening of the episulfide ring of 33 e-h, with sodium acetate followed by acidic hydrolysis, Zemplen de-O-acety lation and acetylation gave the thio disaccharides 4-O-(2',3',4',6'-tetra-O -acetyl-beta-D-galactopyranosyl-, -alpha-D-glucopyranosyl- and -beta-D-gluc opyranosyl)-1,2,3,6-tetra-O-acetyl-5-thio- alpha,beta-L-idopyranoses (38-40 ), 1,2,3-Tri-O-acetyl-4-O-[2',3',4',6'-tetra-O- acetyl-beta-D-galactopyrano syl] -6-deoxy-5thio-alpha,beta-L-idopyranose (37) was obtained by treatment of 4-O-(2',6'-di-O-acety-3',4'- O-isopropylidene-beta-D-galactopyranosyl)- 2,3-O-isopropylidene-6-S- cyano-5-O-sulfonate-6-thio-amehydo-D- glucose dim ethyl acetal potassium salt (32a) with lithium aluminium hydride followed b y acidic hydrolysis and acetylation, The analogous thio maltose and cellobi ose (47c and 47d) were synthesised following a similar strategy (5,6-cyclic sulfate -->episulfide -->thiosugar) from compounds 42a and 42b.