Modular Synthesis of a Tridecasaccharide Motif of Bacteroides vulgatus Lipopolysaccharides against Inflammatory Bowel Diseases through an Orthogonal One-Pot Glycosylation Strategy.

Abstract

Lipopolysaccharides from Bacteroides vulgatus represent interesting targets for the treatment of inflammatory bowel diseases. However, efficient access to long, branched and complex lipopolysaccharides remains challenging. Herein, we report the modular synthesis of a tridecasaccharide from Bacteroides vulgates through an orthogonal one-pot glycosylation strategy based on glycosyl ortho-(1-phenylvinyl)benzoates, which avoids the issues of thioglycoside-based one-pot synthesis. Our approach also features: 1) 5,7-O-di-tert-butylsilylene-directed glycosylation for stereoselective construction of the α-Kdo linkage; 2) hydrogen-bond-mediated aglycone delivery for the stereoselective formation of β-mannosidic bonds; 3) remote anchimeric assistance for stereoselective assembly of the α-fucosyl linkage; 4) several orthogonal one-pot synthetic steps and strategic use of orthogonal protecting groups to streamline oligosaccharide assembly; 5) convergent [1+6+6] one-pot synthesis of the target.