Synthesis of rare sugar isomers through site-selective epimerization

Glycans have diverse physiological functions, ranging from energy storage and structural integrity to cell signalling and the regulation of intracellular processes¹. Although biomass-derived carbohydrates (such as D-glucose, D-xylose and D-galactose) are extracted on commercial scales, and serve as renewable chemical feedstocks and building blocks^2,3, there are hundreds of distinct monosaccharides that typically cannot be isolated from their natural sources and must instead be prepared through multistep chemical or enzymatic syntheses^4,5. These 'rare' sugars feature prominently in bioactive natural products and pharmaceuticals, including antiviral, antibacterial, anticancer and cardiac drugs^6,7. Here we report the preparation of rare sugar isomers directly from biomass carbohydrates through site-selective epimerization reactions. Mechanistic studies establish that these reactions proceed under kinetic control, through sequential steps of hydrogen-atom abstraction and hydrogen-atom donation mediated by two distinct catalysts. This synthetic strategy provides concise and potentially extensive access to this valuable class of natural compounds.