Unlocking C–OH Bond Activation for Radical C-Glycosylation of Native Saccharides

Sheng Wang; Peng Guo; Xing-Zhong Shu

doi:10.1055/a-2572-0983

Synlett, Table of Contents

Synlett 2025; 36(12): 1632-1636
DOI: 10.1055/a-2572-0983

synpacts

Unlocking C–OH Bond Activation for Radical C-Glycosylation of Native Saccharides

Sheng Wang

^aState Key Laboratory of Applied Organic Chemistry (SKLAOC), College of Chemistry and Chemical Engineering, Lanzhou University, 222 South Tianshui Road, Lanzhou, 730000, P. R. of China

,

Peng Guo∗

^aState Key Laboratory of Applied Organic Chemistry (SKLAOC), College of Chemistry and Chemical Engineering, Lanzhou University, 222 South Tianshui Road, Lanzhou, 730000, P. R. of China

^bSchool of Basic Medical Science, Lanzhou University, 222 South Tianshui Road, Lanzhou, 730000, P. R. of China

,

Xing-Zhong Shu ∗

^aState Key Laboratory of Applied Organic Chemistry (SKLAOC), College of Chemistry and Chemical Engineering, Lanzhou University, 222 South Tianshui Road, Lanzhou, 730000, P. R. of China

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Abstract

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Abstract

Due to their enhanced metabolic stability, C-glycosides are valuable structural motifs in bioactive natural products and pharmaceuticals. However, direct C-glycosylation of native saccharides remains a significant challenge due to the inert nature of the C–OH bond and the inherent selectivity issues arising from multiple hydroxy groups. In this Synpacts article, we highlight our recent development of a titanium-catalyzed radical C-glycosylation strategy that enables selective C–OH bond activation without prefunctionalization. By leveraging a Cp*TiCl₃/Zn system, this method generates glycosyl radicals under mild conditions, facilitating stereoselective C-glycosylation with electron-deficient alkenes. The approach exhibits a broad substrate scope that includes monosaccharides, disaccharides, and complex bioactive molecules, offering significant potential utility in glycodrug discovery. Radical stabilization and stereoelectronic effects drive the observed axial selectivity (>20:1). This work establishes a powerful and practical platform for C-glycoside synthesis, addressing long-standing challenges in carbohydrate functionalization and opening new avenues for radical-mediated glycosylation strategies.

Key words

glycosylation - glycosides - titanium catalysis - radical reaction - Giese reaction

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References

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