New, efficient glycosylation method for oligosaccharide synthesis under neutral conditions: Preparation and use of new DISAL donors

Efficient, stereoselective glycosylation methods are required for the synth esis of complex oligosaccharides as tools in glycobiology. All glycosylatio n methods, which have found wide acceptance, rely on Lewis acid activation of glycosyl donors prior to glycosylation. Here, we present a new and effic ient method for glycosylation under neutral or mildly basic conditions. Gly cosides of methyl 2-hydroxy-3,5-dinitrobenzoate (DISAL) and its para. regio isomer, methyl 4-hydroxy-3,5-dinitrobenzoate, were prepared by nucleophilic aromatic substitution. In a first demonstration of their potential as glyc osyl donors, stereospecific glycosylation of methanol was achieved. In the glycosylation of more hindered alcohols, the beta -donor proved more reacti ve, and alpha -glucosides were predominantly formed. Glycosylation of prote cted monosaccharides, with free 6-OH or 3-OH, proceeded smoothly in 1-methy l-2-pyrrolidinone (NMP) at 40-60 degreesC in the absence of Lewis acids and bases in good to excellent yields. Glycosylation of 3-OH gave the alpha -l inked disaccharide only.