Metal-catalyzed intramolecular nitrogen atom delivery will be developed as a method for the synthesis of a wide range of 2-amino sugar frameworks, including the disaccharide portion of the chitinase inhibitor allosamidin. Conditions will be optimized for conversion of glycal carbamates to the corresponding metalla acyl nitrenes, initiating nitrogen insertion into the electron-rich glycal alkene, followed by in situ glycosylation with a minimum of glycosyl acceptor. The overall amidoglycosylation process will provide 2-amino sugar building blocks with high stereoselectivity in the new C-2-N connection as well as at the anomeric center. The products will be elaborated to function as either glycosyl donors or acceptors for di- and oligosaccharide synthesis. Iterative application of the metal-catalyzed amidoglycosylation methodology will allow completion of a concise synthetic route to the allosamidin disaccharide. The flexible synthesis plan will enable late-stage attachment of allosamidin head group analogues to the disaccharide, offering chemical probes for the study of chitinase structure, mechanism, and inhibition. A crucial element of the research effort will be the continuing involvement of Barnard College undergraduates in all aspects of the project, enabling students to contribute fundamental knowledge in the field while encouraging them to pursue careers in chemistry and the health-related professions. ? ?
| Bodner, Rena; Marcellino, Bridget K; Severino, Alexandra et al. (2005) Alpha-N-acetylmannosamine (ManNAc) synthesis via rhodium(II)-catalyzed oxidative cyclization of glucal 3-carbamates. J Org Chem 70:3988-96 |
