Synthesis of Thiodisaccharide Sulfoxides and Sulfones – Determination of the Configuration of the Sulfur Stereocentre

Abstract

The oxidation of per-O-acetyl (1,3)- and (1,4)-linked thiodisaccharides containing glucose, gulose and galactose residues, with an excess of m-chloroperbenzoic acid afforded the corresponding sulfoxides or sulfones. The latter were formed when the oxidation reaction was conducted for longer times. The sulfoxides were obtained as diastereomeric mixtures due to the chirality of the sulfur atom. Both diastereoisomers of the (1,3)-thiodisaccharides S-oxides were isolated by column chromatography, while the S-(1,4)-linked analogues could not be separated. The absolute configuration of the sulfur stereocenter of sulfoxides was assigned using NMR spectroscopy and taking into account the preferred conformations of the molecules and the shielding/deshielding of proton signals caused by anisotropy of the S=O bond and related effects. Most of the thiodisaccharide S-oxides were successfully O-deacetylated with MeOH-Et3N-H2O, whereas the sulfone underwent elimination reactions. Therefore, the oxidation was performed on the free thiodisaccharides, and the corresponding sulfones were obtained in very good yields.