C-glycoside synthesis via radical cross-coupling of glycohydrazides

Carbohydrates are among the most abundant and structurally diverse biomolecules in nature, playing central roles in energy storage, molecular recognition, and cell signaling. Within this domain, C-glycosides 1-3 , in which the oxygen atom of the glycosidic bond in O-glycosides is replaced by carbon, have emerged as valuable motifs in medicinal chemistry due to their resistance to enzymatic hydrolysis 2,4 . Of particular importance are C-aryl glycosides, exemplified by the SGLT2 inhibitors dapagliflozin, canagliflozin, and empagliflozin, which are frontline therapies for type 2 diabetes 5-7 . However, scalable syntheses of C-aryl glycosides have traditionally relied on protected sugar derivatives, lengthy sequences, or conventional cross-couplings that often suffer from poor selectivity, limited scope, and extensive protecting-group manipulation 6 . Herein, we report a practical approach to C-aryl glycosides using glycosyl sulfonyl hydrazides as redox-neutral radical precursors for cross-coupling. Prepared directly from unprotected native sugars, these reagents generate glycosyl radicals under mild conditions and enable efficient access to diverse C-aryl glycosides, including all approved SGLT2 inhibitors, natural products such as salmochelins and neopetrosins, and medicinally relevant probes. …