Direct radical functionalization of native sugars

作者：Yi Jiang, Yi Wei, Qianyi Zhou, Guo‐Quan Sun, Xia‐Ping Fu, Nikita Levin, Yijun Zhang, Wenqiang Liu, NingXi Song, Shabaz Mohammed, Benjamin G. Davis, Ming Joo Koh · 发表于：Nature · 年份：2024 · DOI：10.1038/s41586-024-07548-0 · 被引用次数：125 · 研究领域：Carbohydrate Chemistry and Synthesis、Chemical Synthesis and Analysis、Glycosylation and Glycoproteins Research

Abstract Naturally occurring (native) sugars and carbohydrates contain numerous hydroxyl groups of similar reactivity 1,2 . Chemists, therefore, rely typically on laborious, multi-step protecting-group strategies 3 to convert these renewable feedstocks into reagents (glycosyl donors) to make glycans. The direct transformation of native sugars to complex saccharides remains a notable challenge. Here we describe a photoinduced approach to achieve site- and stereoselective chemical glycosylation from widely available native sugar building blocks, which through homolytic (one-electron) chemistry bypasses unnecessary hydroxyl group masking and manipulation. This process is reminiscent of nature in its regiocontrolled generation of a transient glycosyl donor, followed by radical-based cross-coupling with electrophiles on activation with light. Through selective anomeric functionalization of mono- and oligosaccharides, this protecting-group-free ‘cap and glycosylate’ approach offers straightforward access to a wide array of metabolically robust glycosyl compounds. Owing to its biocompatibility, the method was extended to the direct post-translational glycosylation of proteins.