NBS ‐Mediated Mitsunobu Glycosylation: Facile Assembly of N ‐Glycosides from Unprotected Sugars and Application to Polysaccharide Analysis

Abstract

Comprehensive Summary Chemical N ‐glycosylation is a crucial step in the synthesis of complex N ‐glycosides, particularly nucleosides. However, traditional carbohydrate chemistry often relies heavily on protecting groups, which can lead to cumbersome, time‐consuming substrate preparation. Herein, we present a protecting‐group‐free glycosylation strategy that utilizes unprotected sugars as glycosyl donors through an N ‐bromosuccinimide (NBS)‐mediated Mitsunobu reaction. This protocol features elimination of protection‐deprotection manipulations, a broad substrate scope (compatible with a variety of unprotected monosaccharides, including ribose, arabinose, mannose, fructose, rhamnose, lyxose, xylose, galactose, glucose, and fucose), and excellent 1,2 ‐trans ‐stereoselectivity. Importantly, this method has been successfully used for monosaccharide composition analysis of polysaccharides in traditional Chinese medicine (TCM).