Radical Cross-Coupling Enables C-Glycoside Synthesis

A new method for synthesizing C-glycosides has been reported by researchers, utilizing a radical cross-coupling reaction between glycohydrazides and various organic electrophiles. This breakthrough, published online in Nature on June 22, 2026, offers a more efficient and versatile route to these important carbohydrate derivatives compared to existing methods. C-glycosides are a class of compounds with significant biological activity and are found in numerous natural products, making their synthesis a key area of research in organic chemistry and medicinal chemistry.

The developed protocol involves the generation of a glyco-radical intermediate from the glycohydrazide precursor, which then undergoes a cross-coupling reaction with an electrophilic coupling partner. This approach circumvents common challenges associated with traditional C-glycoside synthesis, such as the need for harsh reaction conditions or the limited scope of applicable substrates. The study details the optimization of reaction parameters, including the choice of radical initiator, solvent, and temperature, to achieve high yields and stereoselectivity.

Further investigations presented in the Nature publication demonstrate the broad applicability of this methodology. The researchers successfully synthesized a range of C-glycosides incorporating diverse structural motifs, including aryl, alkyl, and heteroaryl groups. This versatility is crucial for accessing complex carbohydrate structures relevant to drug discovery and the development of novel materials. The efficiency of the reaction was validated through the synthesis of known biologically active C-glycosides, confirming the practical utility of the new synthetic strategy. The publication's DOI is 10.1038/s41586-026-10807-x.