In this CAREER project funded by the Chemical Synthesis Program of the Chemistry Division, Professor Mingji Dai of the Department of Chemistry at Purdue University is developing new palladium-catalyzed carbonylation methodologies and strategies for the syntheses of bioactive natural products. The goal of this research is to use cheap and abundant carbon monoxide as the starting material to made more advanced and complicated molecular structures with the aid of a small amount of palladium catalyst. These newly developed methodologies and strategies streamline the syntheses of important natural products, which are either organic insecticides or promising lead compounds for drug discovery. This work is expected to advance the science of preparing complicated molecular structures. The project centers on the use of palladium catalysis and extends known methods to complex natural product syntheses. In addition to training postdoctoral researchers, graduate students, and undergraduate students, the educational plan includes outreach to educate Indiana high school science teachers and students about catalysis and natural products, as well as their impact of our everyday lives.
Alkyl-palladium species react readily with carbon monoxide to generate reactive acyl-palladium species. In this project, novel reaction modes are developed to trap these in situ generated acyl-palladium species to construct complex and important structures that are otherwise difficult to access. Specifically, Professor Dai is developing (i) palladium-catalyzed tandem alkoxycarbonylative macrolactonization to synthesize tetrahydropyran/tetrahydrofuran-containing bridged macrolides with anticancer activity, (ii) palladium-catalyzed carbonylative Heck macrolactonization to synthesize fused macrolides with insecticidal activity, and (iii) palladium-catalyzed C-C bond cleavage carbonylative lactonizations to synthesize oxaspirolactones with potent activity against drug resistant bacteria. The synthetic applications have the potential impact to combat human diseases and improve agricultural food production. The research is well suited to the education and training of a diverse group of students and scholars.
