Citation: Xianrong Zeng, Hui-Ying Shi, Huiqian Huang, Zhaobin Wang. Photo-induced stereoselective 2-deoxyglycoside synthesis from glycals with carboxylic acids and alcohols[J]. Chinese Chemical Letters, ;2026, 37(5): 111615. doi: 10.1016/j.cclet.2025.111615 shu

Photo-induced stereoselective 2-deoxyglycoside synthesis from glycals with carboxylic acids and alcohols

Xianrong Zeng ^{a, b, 1} ,
Hui-Ying Shi ^{c, 1} ,
Huiqian Huang ^{d, *,} ,
Zhaobin Wang ^{b, e, *,}

a.
Department of Chemistry, Zhejiang University, Hangzhou 310058, China
b.
Key Laboratory of Precise Synthesis of Functional Molecules of Zhejiang Province, Department of Chemistry, School of Science and Research Center for Industries of the Future, Westlake University, Hangzhou 310030, China
c.
NHC and CAMS Key Laboratory of Medical Neurobiology, MOE Frontier Science Center for Brain Science and Brain-machine Integration, School of Brain Science and Brain Medicine, Zhejiang University, Hangzhou 310058, China
d.
Basic and Translational Research Center, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China
e.
Institute of Natural Sciences, Westlake Institute for Advanced Study, Hangzhou 310024, China

hhq0301@zju.edu.cn

wangzhaobin@westlake.edu.cn

Received Date: 16 April 2025
Revised Date: 27 June 2025
Accepted Date: 19 July 2025
Available Online: 21 July 2025

Figures(8)

Synthesizing 2-deoxyglycosides, prevalent motifs in bioactive molecules, presents significant challenges in stereocontrol and functional group tolerance. We report a metal-free, photo-induced O-glycosylation of glycals using acridinium salts under visible light. This method effectively couples diverse glycals with both carboxylic acids and alcohols, providing facile access to α-2-deoxyglycosides under mild conditions with broad substrate scope and functional group compatibility. The protocol exhibits high α-stereoselectivity with carboxylic acids and moderate α-selectivity with alcohols, enabling late-stage functionalization of complex molecules, including amino acids, peptides, and drugs. Mechanistic experiments implicate the possible involvement of radical intermediates, potentially operating via a chain reaction. Notably, 2-deoxyglycosylation of NSAIDs using this method enhanced their neuroprotective properties in vitro. This photo-induced strategy offers a practical and versatile platform for accessing complex 2-deoxyglycans relevant to medicinal chemistry and chemical biology.
- 2-Deoxyglycoside,
- O-Glycosylation,
- Carboxylic acids,
- Alcohols,
- Glycals
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