Issue 27, 2023

Stereoselective alkyl C-glycosylation of glycosyl esters via anomeric C–O bond homolysis: efficient access to C-glycosyl amino acids and C-glycosyl peptides

Abstract

C-Glycosyl peptides possess excellent metabolic stability and therapeutic properties and thus play critical roles in biological studies as well as drug discoveries. However, the limited accessibility of C-glycosyl amino acids has significantly hindered the broader research of their structural features and mode of action. Herein, for the first time we disclose a novel visible-light-driven radical conjugate addition of 1,4-dihydropyridine (DHP)-derived glycosyl esters with dehydroalanine derivatives, generating C-glycosyl amino acids and C-glycosyl peptides in good yields with excellent stereoselectivities. Redox-active glycosyl esters, as readily accessible and bench-stable radical precursors, could be easily converted to glycosyl radicals via anomeric C(sp3)–O bond homolysis under mild conditions. Importantly, the generality and practicality of this transformation were fully demonstrated in >40 examples including 2-dexosugars, oligosaccharides, oligopeptides, and complex drug molecules. Given its mild reaction conditions, robust sugar scope, and high anomeric control and diastereoselectivity, the method presented herein could find widespread utility in the preparation of C(sp3)-linked sugar-based peptidomimetics.

Graphical abstract: Stereoselective alkyl C-glycosylation of glycosyl esters via anomeric C–O bond homolysis: efficient access to C-glycosyl amino acids and C-glycosyl peptides

Supplementary files

Article information

Article type
Edge Article
Submitted
18 Apr 2023
Accepted
18 Jun 2023
First published
20 Jun 2023
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY-NC license

Chem. Sci., 2023,14, 7569-7580

Stereoselective alkyl C-glycosylation of glycosyl esters via anomeric C–O bond homolysis: efficient access to C-glycosyl amino acids and C-glycosyl peptides

A. Chen, S. Zhao, Y. Han, Z. Zhou, B. Yang, L. Xie, M. A. Walczak and F. Zhu, Chem. Sci., 2023, 14, 7569 DOI: 10.1039/D3SC01995K

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