A team of chemists has reported a new method for constructing C‑glycosidic bonds—linkages that join sugars to carbon atoms rather than oxygen—by employing radical cross‑coupling of glycohydrazides. The approach, detailed in a paper published online June 22, 2026 in Nature, offers a modular and scalable route to C‑glycosides, a class of compounds prized for their stability and therapeutic potential.
The researchers designed glycohydrazide precursors that, when activated by a nickel catalyst and a photoredox system, generate carbon‑centered radicals. These radicals undergo cross‑coupling with a wide range of aryl and alkyl halides, furnishing C‑glycosides in yields up to 90 percent. The method tolerates diverse functional groups, including esters, nitriles, and heterocycles, and can be applied to complex carbohydrate scaffolds without protecting‑group manipulations.
“C‑glycosides are highly sought after in drug discovery because they resist enzymatic cleavage,” the authors noted. “Our strategy provides a general platform for accessing these motifs directly from readily available sugars.”
The study also demonstrated the utility of the protocol in late‑stage functionalization of biologically active molecules, converting natural product derivatives into C‑glycosylated analogues that retained or enhanced activity in preliminary assays.
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If the technique proves robust across larger‑scale operations, it could streamline the synthesis of carbohydrate‑based pharmaceuticals, which often rely on labor‑intensive protecting‑group strategies. By leveraging radical chemistry, the method sidesteps the need for pre‑activated sugar donors, potentially reducing cost and environmental impact. However, the reliance on nickel catalysis and photoredox conditions may pose challenges for industrial adoption, particularly regarding catalyst recovery and reaction scalability. Further validation in pilot‑plant settings will be essential to gauge commercial viability.
Sources
Nature, “C‑glycoside synthesis via radical cross‑coupling of glycohydrazides,” published online 22 June 2026, https://www.nature.com/articles/s41586-026-10807-x
Source: Nature – Original article
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Story synopsis gathered from: Nature — source
