Leveraging Cyclopropanols in Natural Product Synthesis

Wayne State University, Detroit MI

Investigators

Abstract

With the support of the Chemical Synthesis program of the Division of Chemistry, Professor Jin Cha of Wayne State University is developing efficient routes to important molecules which are utilized in organic or medicinal chemistry. Starting with readily available three-membered ring compounds, the research plan builds complex molecules in a modular approach to construct naturally occurring molecules endowed with desirable properties. The proposed work builds on a key modification in the initial three-membered ring formation to pave the way for new chemical syntheses. These studies will have potential for broader societal benefits, as convergent, environmentally benign and sustainable syntheses offer enabling tools in pharmaceutical, chemical, agricultural industry, and materials science. This project will provide excellent training for coworkers, from undergraduate research participants to post-doctoral fellows, including those from groups historically underrepresented in STEM (science, technology, engineering and mathematics) fields. With the support of the Chemical Synthesis program of the Division of Chemistry, Professor Cha of Wayne State University is studying an efficient synthesis of natural products with particular emphasis on efficiency and selectivity. Coupling (union) of two polyfunctional fragments lends itself to practical syntheses of complex molecules. The proposed study will focus on the development and application of cross-coupling reactions of cyclopropanols or the related titanacyclopropanes to develop concise synthetic routes. The Cha group will continue to utilize cyclopropanols as a unique family of nonracemic and attractively functionalized homologous enol equivalents in the C–C bond formation. Transition metal-catalyzed cross-coupling reactions of two segments include C-acylation, SN2’ alkylation, alkenylation, and alkynylation of cyclopropanols. The preparative power of the key synthetic methods are to be highlighted in projected concise total syntheses of an array of structurally novel and biologically important natural products. Among these targets are included gephyrotoxin, alkaloid 261C, scholarisine A, artemisinin, and mitomycin C. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.