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

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. A joined up approach: Unusual stability of picoloyl protected TMS glycosides for 1,1′‐glycosylation has been observed. This property was used for the synthesis of nonsymmetrical 1,1′‐disaccharides with diverse configurations and sugar components (see scheme).