Stereoretentive and Regioselective Late-Stage C-H Glycosylation
Shuai Chen1, Bo Yang1,2, Yaoyong Zeng3
1Frontiers Science Center for Transformative Molecules, Center for Chemical Glycobiology, State Key Laboratory of Synergistic Chem-Bio Synthesis, Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs, School of Chemistry and Chemical Engineering, Zhangjiang Institute for Advanced Study, Shanghai Jiao Tong University, Shanghai 200240, P. R. China.
Journal of the American Chemical Society
|June 18, 2026
Summary
This study introduces a novel late-stage C-H glycosylation platform for drug discovery. It enables precise synthesis of diverse C-glycosylated drug analogs, enhancing antitumor efficacy and neuroprotection in vivo.
Area of Science:
- Medicinal Chemistry
- Organic Synthesis
- Drug Discovery
Background:
- Glycosylation modulates drug properties, but late-stage C-H glycosylation is challenging.
- Existing methods lack site- and stereoselectivity, limiting general use.
Purpose of the Study:
- Develop a general platform for late-stage C-H glycosylation.
- Enable precise synthesis of diverse C-glycosylated drug analogs.
- Explore the therapeutic potential of C-glycosylated compounds.
Main Methods:
- Integrated aromatic C-H thianthrenation with palladium-catalyzed glycosyl cross-coupling.
- Utilized complementary C-H and C-B thianthrenation pathways.
- Performed in vivo studies in Caenorhabditis elegans.
Main Results:
- Achieved site- and stereoselective synthesis of α- and β-C-glycosylated drug derivatives.
- Demonstrated direct coupling with unprotected sugars.
- Showcased modulated antitumor efficacy and neuroprotection.
- Identified glycosyl stannanes with antitumor and Huntington's disease therapeutic potential.
Conclusions:
- The developed platform offers a general and precise strategy for drug glycodiversification.
- Accelerates sugar-based drug discovery and expands late-stage functionalization tools.
- Highlights the therapeutic potential of C-glycosylated small molecules.
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