Carbonylation Methodologies and Strategies for Building Complex Chemical Structures

Emory University, Atlanta GA

Investigators

Abstract

With the support of the Chemical Synthesis Program in the Division of Chemistry, Professor Mingji Dai of Emory University is developing new catalytic reactions to make complex and medicinally important molecules using cheap and sustainable carbon monoxide as a one-carbon linchpin. Natural products are indispensable in the development of modern medicinal chemistry. However, the natural scarcity and the complexity of the chemical structures of many promising natural products are major hurdles to their scale-up for full exploration and exploitation as potential pharmaceutical agents. The reactions that Professor Dai and his research group are investigating are helping to address this problem by providing streamlined and sustainable ways to make important natural products and related molecules. The products of these studies are also being shared with collaborators to investigate their biological significance, including anticancer activity. Professor Dai is also providing valuable training to a diverse group of postdoctoral researchers, graduate students, and undergraduate students and preparing these individuals for future careers in the chemical sciences. Professor Dai and his research team are investigating innovative carbonylation reactions with transition metal catalysis to rapidly build structural complexity. These new methodologies are then being applied in synthetic sequences targeted toward challenging natural and non-natural products with desirable characteristics for medicinal studies. In one branch of the research program, enabling palladium-catalyzed carbonylative transformations are being developed and utilized to synthesize complex and polycyclic anticancer natural products from plants used in herbal medicine. In a related but distinct part of the project, efforts will be focused on replacing the aforementioned palladium with nickel catalysis to both develop more economical and sustainable processes as well as to enable different carbonylative lactonizations to synthesize various lactones and their derivatives. In the third portion of the program, new transition metal-catalyzed carbonylative macrolactonization reactions are being explored to synthesize complex macrolides and their derivatives. The program promises to develop new modalities toward natural product synthesis and elaboration with broad potential impact in synthesis, chemical biology and medicinal chemistry. 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.