CAREER: Efficient Synthesis of Biologically Relevant Cyclic and Polycyclic Terpenoid Compounds Using Alkyne Cyclizations

Board Of Regents, Nshe, Obo University Of Nevada, Reno, Reno NV

Investigators

Abstract

With this CAREER Award, the Synthesis Program supports the research of Professor Wesley A. Chalifoux of the University of Nevada, Reno. Professor Chalifoux develops new chemical tools for the efficient synthesis of biologically active compounds. New methodology developed in this research focuses on the application of ynones for the efficient construction of complex cyclic compounds. Ynones are substances in which a carbon-carbon triple bond (an alkyne) is connected to a carbon oxygen double bond (a carbonyl group). This connection enhances chemical reactivity in bimolecular addition reactions. New strategies which are developed in this research have applications in the area of pharmaceutical synthesis and the field of medicine through the generation of biologically-relevant compound libraries. As the educational component of this project, Professor Chalifoux develops an outreach program that focuses on the mentoring of middle and high school students from low-income, first-generation college families as well as groups that are underrepresented in science. The project builds connections with middle and high schools located in the Reno, Nevada area. Visiting high school students work closely with graduate and undergraduate chemistry students in science-related activities associated with research projects within the Chalifoux group. In this project, cyclization and cycloaddition reactions of alkynes and alkynones are explored. This research develops an operationally simple synthetic methodology that converts readily available alkyne, diyne and diene starting materials into complex cyclic and polycyclic target molecules. Simple conjugated alkynes and more complex conjugated and cross-conjugated polyynes are explored as substrates for Diels-Alder cycloaddition reactions. These are further elaborated in multicomponent/tandem cyclization reactions that are designed to generate multiple new carbon-carbon bonds and rings in a single reaction step, with regio- and stereochemical control. This research has broad applications in the area of pharmaceutical synthesis and the field of medicine through the rapid generation of biologically relevant compound libraries. In addition to activities at the middle and high schools, the CAREER Award supports summer research activities at the University of Nevada. This improves recruitment of underrepresented students into Science, Technology, Engineering and Mathematical (STEM) careers and increases retention of students in the sciences.