A new, efficient glycosylation method for oligosaccharide synthesis under neutral conditions: preparation and use of new DISAL donors.

Abstract

Efficient, stereoselective glycosylation methods are required for the synthesis of complex oligosaccharides as tools in glycobiology. All glycosylation methods, which have found wide acceptance, rely on Lewis acid activation of glycosyl donors prior to glycosylation. Here, we present a new and efficient method for glycosylation under neutral or mildly basic conditions. Glycosides of methyl 2-hydroxy-3,5-dinitrobenzoate (DISAL) and its para regioisomer, methyl 4-hydroxy-3,5-dinitrobenzoate, were prepared by nucleophilic aromatic substitution. In a first demonstration of their potential as glycosyl donors, stereospecific glycosylation of methanol was achieved. In the glycosylation of more hindered alcohols, the beta-donor proved more reactive, and alpha-glucosides were predominantly formed. Glycosylation of protected monosaccharides, with free 6-OH or 3-OH, proceeded smoothly in 1-methyl-2-pyrrolidinone (NMP) at 40-60 degrees C in the absence of Lewis acids and bases in good to excellent yields. Glycosylation of 3-OH gave the alpha-linked disaccharide only.