Unusually Stable Picoloyl-Protected Trimethylsilyl Glycosides for Nonsymmetrical 1,1-Glycosylation and Synthesis of 1,1-Disaccharides with Diverse Configurations

Abstract

Nonsymmetrical 1,1-disaccharides and related derivatives constitute structural components in various glycolipids and natural products. Some of these compounds have been shown to exhibit appealing biological properties. We report a direct yet stereoselective 1,1-glycosylation strategy for the synthesis of nonsymmetrical 1,1-disaccharides with diverse configurations and sugar components. The strategy is based on the joined forces of a new class of configurationally stable glycoside acceptors and stereodirecting thioglycoside donors. The new glycoside acceptors feature a picoloyl (Pico) protecting group at the remote C4/C3 position that confers unusual stability on TMS glycosides under acidic conditions.