De Novo Asymmetric Synthesis of Natural and Unnatural Carbohydrate Motifs

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The Chemical Synthesis Program of the Chemistry Division supports the project by Professor George O'Doherty. Professor O'Doherty is a faculty member in the Department of Chemistry and Chemical Biology at Northeastern University. He and his group are working to develop practical synthetic approaches to oligo-cyclitols. Cyclitols are structural mimics of carbohydrates that are resistant to metabolism. In contrast to the other biological polymers (e.g., DNA and proteins), there are no practical methods for the construction of stable analogues of the oligosaccharides. To address this need, the O'Doherty group is developing a novel method of monomer assembly to prepare oligo-cyclitols. The O'Doherty group is uniquely positioned to carry out this research, as this project is based on their previously established method for the synthesis of oligosaccharides. The project provides access to novel structures for biological studies. In addition, the research program offers an excellent opportunity to train undergraduate and graduate students, as well as postdoctoral associates in the state of the art methods for complex molecule synthesis. This program impacts society at numerous levels: making carbohydrate synthesis greener, improving drug discovery, and furthering student training. This research has the potential to revolutionize the way oligosaccharide structures are used in medicinal and biological chemistry studies. While methods for exo-C-glycosides syntheses have been developed, the impracticality of these syntheses has limited their use in medicinal chemistry studies. Dr. O'Doherty's approach to cyclitols (aka, endo-C-glycosides or 5a-carbasugars), mirrors the broadly successful approach to oligosaccharides, both of which rely on the use of enantio- and diastereo-selective catalytic reactions (e.g., transition metal or bimetallic catalyzed allylation). The de novo approaches start with a significantly simplified structure and sequentially increases its stereochemical and functional complexity to a range of structures, which in turn enables medicinal chemistry and chemical biology structure-activity relationship studies. This program impacts society at numerous levels: making carbohydrate synthesis greener, improving drug discovery, and furthering student training.