Direct radical functionalization of native sugars

• 成果类型: Article
• 署名作者: Jiang, Yi; Wei, Yi; Zhou, Qian-Yi; Sun, Guo-Quan; Fu, Xia-Ping; Levin, Nikita; Zhang, Yijun; Liu, Wen-Qiang; Song, Ningxi; Mohammed, Shabaz; Davis, Benjamin G.; Koh, Ming Joo
• 署名单位: National University of Singapore; Rosalind Franklin Institute; University of Oxford; Southern University of Science & Technology; University of Oxford; University of Oxford
• 刊物名称: Nature
• ISSN/ISSBN: 0028-5903
• DOI: 10.1038/s41586-024-07548-0
• 发表日期: 2024-07-11
• 关键词: glycosylation; activation; arylation

摘要

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. A radical-based method for functionalizing native sugars shows a way to remove typical protecting-group manipulations.