Carbonylation Methodologies and Strategies for Building Complex Chemical Structures

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With the support of the Chemical Synthesis Program in the Division of Chemistry, Professor Mingji Dai of Purdue University is developing new ways to make complex and medicinally important molecules using carbon monoxide as a one-carbon linchpin and a palladium catalyst to form new bonds. Complex natural products and natural product-like molecules are indispensable in drug discovery. However, their structural complexity necessitates the development of new catalytic synthetic methods for their synthesis. The reactions that Professor Dai and his research group are investigating are helping to address this problem by providing streamlined methods to access these important targets. The products of these studies are also being shared with collaborators to investigate their biological significance. Simultaneously, this work is being used for the education and training of a diverse group of students and scholars.Professor Dai and his research team are investigating how to generate and intercept acyl-palladium species to design new reactions that rapidly increase structural complexity. This new synthetic methodology is then being applied in synthetic sequences that target challenging natural and non-natural products with potentially desirable characteristics for medicinal studies. In one branch of the research program, transformations involving palladium-catalyzed tandem carbon-carbon bond cleavage and carbonylative lactonization are being studied to synthesize fused bicyclic lactones including complex Stemona alkaloids isolated from plants used in herbal medicine. In a related but distinct part of the project, palladium-catalyzed carbonylative macrolactonization is being explored to synthesize complex macrolides and their derivatives. In the third portion of the program, palladium-catalyzed tandem, carbonylative cyclization is being explored to synthesize natural products that feature electrophilic moieties with the potential for covalent protein modification. Professor Dai is also providing valuable training to postdoctoral researchers, graduate students, and undergraduate students and preparing these individuals for future careers in the chemical sciences.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.