A new method will be developed for the synthesis of 2-amino-2-deoxy sugars, a class of compounds that includes many biologically and medicinally important substances. In a highly stereoselective process, glycal azidoformates will undergo intramolecular carbon-carbon double bond aziridination upon conversion to the acyl nitrenes. Both photolytic and metal-catalyzed pathways will be explored to initiate nitrene formation. The resulting highly reactive aziridines are expected to serve as in situ glycosyl donors in the formation of di- and oligosaccharides, with nitrogen incorporated at the C-2 position of the sugar subunits. This unique synthetic sequence will be investigated using a range of glycal azidoformates, prepared from the carbonyl imidazolides via a mild, dialkyltin oxide-promoted reaction with trirnethylsilyl azide. The proposed studies will enlarge the array of synthetic tools available for the chemical preparation of biologically significant 2-aminosaccharides, including the di-N-acetylallosamine portion of the chitinase inhibitor allosamidin, a compound that strongly curtails insect growth and has potential as a species-selective fungicide. In addition, this work will extend fundamental knowledge of azidoformate and acyl nitrene reactivity. Another important outcome of the project will be to involve undergraduate students in all facets of the proposed research, encouraging Barnard College's best and brightest women to pursue careers in the chemical sciences.
| 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 |
