With this award, the Chemical Synthesis Program of the Division of Chemistry is funding Professor Nessan J. Kerrigan of the Department of Chemistry at Oakland University to explore the development of new methods for the synthesis of gamma-lactones. Gamma-lactones are medicinally relevant compounds, acting as key constituents of many biologically active molecules (e.g., antibiotics and HIV-1 inhibitors) and also with the potential to function as conduits for the synthesis of other biologically interesting molecules. The development of methods to prepare structural motifs commonly found in natural products and biological active synthetics has great importance for both the academic and the industrial sectors, both in pharma and in biotechnology. The broader impacts of this project also involve technical training of students, from the undergraduate to post-doctoral levels, including those from groups historically underrepresented in the sciences.
Three different strategies are being pursued for the development of enantioselective variants of gamma-lactone forming reactions from sulfoxonium salts. Current methods for the synthesis of gamma-lactones are often characterized by multistep approaches, limited substrate scope, and modest diastereoselectivity or enantioselectivity. The Kerrigan research group has developed a method for the diastereoselective synthesis of gamma-lactones bearing an alpha-quaternary stereogenic center, through the reaction of sulfoxonium ylides, aldehydes and ketenes (the ?3-component reaction?). It features an interesting [3,3]-sigmatropic rearrangement as the key step. Under this project, the Kerrigan research team plans to explore the scope of the reaction e.g., including an examination of stabilized ylides, semi-stabilized ylides, and monosubstituted ketenes. Professor Kerrigan's group is investigating enantioenriched aminosulfoxonium salts, chiral Koga amines, and chiral Bronsted acids (chiral hydrogen bond donor catalysts) for asymmetric induction in the gamma-lactone-forming reactions. Successful development of the project has the potential to provide as it proposes efficient and inexpensive access to a number of desirable 5-membered cyclic synthons.
