Syntheses stereoselectives de 1-thioglycosides

Abstract

2,3,4,6-Tetra- O-acetyl-β- d-mannopyranosyl chloride ( 2) was obtained in 70% yield by the action of lithium chloride on 2,3,4,6-tetra- O-acetyl-α- d-mannopyranosyl bromide ( 1) in hexamethylphosphoric triamide. p-Nitrobenzenethiol reacted with 1 and 2 as well as with 2,3,4,6-tetra- O-acetyl-α- d-glucopyranosyl bromide ( 9) or its β- d-chloro analog ( 10), giving exclusively and in good yield the corresponding p-nitrophenyl 1-thioglycosides of inverted anomeric configuration. The 1,2- cis- d-manno and - gluco p-nitrophenylglycosides were likewise prepared. α- d-Glucopyranosyl 1-thio-α- d-glucopyranoside was similarly obtained by the action of the sodium salt of 1-thio-α- d-glucopyranose on the β-chloride 10 in hexamethylphosphoric triamide, or by treatment of 10 with sodium sulfide, with subsequent deacetylation. Analogous procedures allowed the preparation of β- d-mannopyranosyl 1-thio-β- d-mann opyranoside, the corresponding α,β anomer and α- d-glucopyranosyl 1-thio-α- d-mannopyranoside, starting from bromide 1, 1-thio-α- d-mannopyranose ( 8),and chloride 10, respectively. When acetone was used as solvent, the reaction between 1 and 8 led instead to the α,α anomer. The thio disaccharides that are interglycosidic 4-thio analogs of methyl 4- O-(β- d-galactopyranosyl)-α- d-galactopyranoside, methyl α-cellobioside, and methyl α-maltoside, respectively, were obtained by way of the peracetates of methyl 4-thio-α- d-galactopyranoside and -glucopyranoside by reaction of the corresponding thiolates with tetra- O-acetyl-α- d-galactopyranosyl bromide, bromide 9, or chloride 10, respectively, in hexamethylphosphoric triamide. These 1-thioglycosides, and (1→1)- and (1→4)-thiodisaccharides, were characterized by 1H- and 1 3C-n.m.r. spectroscopy. Correlations were established between the polarity of the sulfur atom and certain proton and carbon chemical-shifts in the 1-thioglycosides in comparison with the O-glycosyl analogs; these correlations permitted in particular the unambigous attribution of anomeric configuration.