Synthesis and conformational analysis of disaccharide analogues containing disulfide and selenosulfide functionalities in the interglycosidic linkages

Abstract

The synthesis of novel disaccharides containing disulfide (methyl-4-S-(β-D-galactopyranosyl-1'-thio)-4-thio-α-D-glucopyranoside (1)) and selenosulfide (methyl-4-Se-(β-D-galactopyranosyl-1'-thio)-4-seleno-α-D-glucopyranoside (2)) functionalities in the interglycosidic linkages is described. The synthetic strategy relied on the reaction of a β-glycosylthiosulfonate with a carbohydrate thiol or selenol nucleophile. The resulting protected β-dihetero-linked disaccharides were deprotected to give the target compounds. The conformational preferences of these dihetero analogues were inferred from NOESY experiments and line-broadening effects in variable-temperature NMR spectra, and are rationalized in terms of molecular orbital theory. Low-energy conformations of these compounds can populate regions of conformational space not usually occupied by β-linked disaccharides, and offer the possibility for presentation of novel ligand topographies.Key words: disaccharides, disulfides, selenosulfides, interglycosidic linkages, conformations, MO explanation.