Direct radical functionalization of native sugars

Journal article

Naturally occurring (native) sugars and carbohydrates contain numerous hydroxyl groups of similar reactivity1, 2. Chemists, therefore, rely typically on laborious, multi-step protecting-group strategies3 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.

Authors: Jiang, Y; Wei, Y; Zhou, Q; Sun, G; Fu, X

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Nature Research
• Journal: Nature
• Volume: 631
• Issue: 8020
• Pages: 319-327
• Publication date: 2024-06-19
• Acceptance date: 2024-05-09
• DOI: 10.1038/s41586-024-07548-0
• EISSN: 1476-4687
• ISSN: 0028-0836
• Language: English