Project Summary Rare and unnatural carbohydrates play an essential role in the potency and selectivity of hundreds of bioactive natural products and pharmaceutical compounds. These scaffolds often feature unusual relative/absolute stereochemistry, pyranose/furanose ring branching, heteroatom substitutions, and varying degrees of deoxygenation. Despite the biological significance of rare and unnatural sugars, synthetic challenges limit access to these important molecules. Due to their functional group density and stereochemical complexity, current syntheses of rare and unnatural sugars require multistep chemical synthesis, and commonly rely on protecting group manipulations to achieve selective reaction outcomes. New, selective methods are needed for the expedient synthesis of pyranose and furanose sugars. This proposal describes the development of selective radical reactions to transform unprotected and minimally protected carbohydrates into diversely functionalized monosaccharides and glycans. We specifically target epimerization reactions and radical rearrangements to achieve broad synthetic access to rare isomeric and deoxygenated sugars, respectively. Using state-of-the-art synthetic, mechanistic and theoretical tools, our approach involves the identification of new catalytic strategies to control bond breaking, bond forming, and radical reorganization steps within the context of complex glycan molecular frameworks. The successful development of this proposed research is anticipated to transform carbohydrate synthesis, dramatically reducing the time and resources necessary to access these complex pharmacophores. Fundamental mechanistic findings revealed en route to this goal are further anticipated to contribute significantly to our understanding of carbohydrate reactivity patterns and to lay the groundwork for catalytic approaches to selective radical functionalization reactions, more broadly.