Catalytic Methods for Stereoselective 1,2-Cis Glycosylation

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PROJECT SUMMARY The field of glycoscience has burgeoned in the last several decades, leading to the identification of many oligosaccharides and glycoconjugates which could serve critical roles in a wide range of biological processes. This rapid growth of knowledge about the function of carbohydrates has attracted increasing attention from biological, pharmacological, and medicinal researchers. Meeting their research demands require access to significant quantities of well- defined bioactive carbohydrates. This has prompted resurgence in synthetic interest, with a particular focus on new approaches to the glycosidic bond. Even with the abundance of elegant reports for stereoselective construction glycosidic linkages, catalytic stereoselective synthesis of α- and β-oligosaccharides and glycoconjugates remains challenging and can only be achieved in the context of a limited set of conditions. One of glycosidic bonds that has historically proven challenging is β-mannosidic bond. This proposal seeks to address this unmet need through the development of a series of predictable and stereoselective α- and β-1,2-cis glycosylation reactions via the merger of photoredox catalysis with nickel catalysis. In each Specific Aim, a different type of directing groups and ligands attached to nickel catalyst will be employed, and a fundamentally different strategy will be investigated to control anomeric selectivity. As such, the proposed methods will provide a variety of new strategies for the construction of challenging α- and β-1,2-cis glycosidic bonds. The proposed stereoselective glycosylation reactions via dual catalysis are significant because these type of glycosidic bonds are widely prevalent in bioactive oligosaccharides and glycoconjugates. The proposed reactions are predictable and stereoselective and conducted under mild and operationally simple conditions without requiring advanced training. Importantly, the new methods have the potential for transforming into automated synthesis.