A Photoinduced, Nickel‐Catalyzed Reaction for the Stereoselective Assembly of C‐ Linked Glycosides and Glycopeptides

作者：Yi Wei, Quanquan Wang, Ming Joo Koh · 发表于：Angewandte Chemie International Edition · 年份：2022 · DOI：10.1002/anie.202214247 · 被引用次数：52 · 研究领域：Carbohydrate Chemistry and Synthesis、Chemical Synthesis and Analysis、Sulfur-Based Synthesis Techniques

Abstract C ‐Alkyl glycosides and glycoproteins exist in natural products and are prized for their role as carbohydrate mimics in drug design. However, a practical strategy that merges glycosyl donors with readily accessible reagents, derived from abundant carboxylic acid and amine feedstocks, is yet to be conceived. Herein, we show that a nickel catalyst promotes C−C coupling between glycosyl halides and aliphatic acids or primary amines (converted into redox‐active electrophiles in one step), in the presence of Hantzsch ester and LiI (or Et 3 N) under blue LED illumination to deliver C ‐alkyl glycosides with high diastereoselectivity. Mechanistic studies support the photoinduced formation of alkyl radicals that react with a glycosyl nickel species generated in situ to facilitate cross‐coupling. Through this manifold, innate CO 2 H and NH 2 motifs embedded within amino acids and oligopeptides are selectively capped and functionalized to afford glycopeptide conjugates through late‐stage glycosylation.