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

• Published in: Angewandte Chemie 2023-05, Vol.135 (22), p.n/a
• Main Authors: Zhang, Yunqin, Wang, Leilei, Zhou, Qingli, Li, Zuoshan, Li, Dan, Yin, Caixia, Wang, Xiufang, Xiao, Guozhi
• Format: Article
• Language: English
• Subjects: Anti-Inflammatory Activity; Assembly; Bacteroides; Benzoates; Benzoic acid; Chemistry; Glycosylation; Inflammatory bowel diseases; Intestine; Lipopolysaccharides; Oligosaccharide Synthesis; Oligosaccharides; Orthogonal One-Pot Glycosylation; Protecting groups; Stereoselectivity; Strategy; Synthesis
• ISSN: 0044-8249; 1521-3757
• DOI: 10.1002/ange.202301351

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. A tridecasaccharide from Bacteroides vulgatus mpk lipopolysaccharides has been synthesized for the first time by a strategy involving orthogonal one‐pot glycosylation reactions based on glycosyl ortho‐(1‐phenylvinyl)benzoates, which precluded issues such as aglycone transfer and the unpleasant odor of thioglycoside‐based orthogonal one‐pot glycosylation.