DISAL glycosyl donors for efficient glycosylations under acidic conditions: Application to solid-phase oligosaccharide synthesis

Abstract

The use of DISAL (methyl dinitrosalicylate) glycosyl donors in efficient Lewis acid-promoted glycosylations is reported. N-Acetyl-D-glucosamine monosaccharide acceptors are successfully glycosylated at O-6 or O-4 using benzyl- and benzoyl-protected DISAL donors in CH₂Cl₂ or nitromethane in the presence of LiClO₄. The resultant disaccharides are isolated in yields ranging from 35 to 93%. Other Lewis acids such as FeCl₃, TMSOTf, or BF₃·Et₂O also prove efficient for glycosylation of the secondary alcohol cyclohexanol. However, for the synthesis of disaccharides, the mild activation by LiClO₄ gives higher yields. This approach is extended to efficient solid-phase glycosylation of a D-glucosamine derivative anchored by the 2-amino group through a Backbone Amide Linker (BAL) to a polystyrene support.