EAPSI:Development of Novel Catalysts for the Chemical Synthesis of Bioactive Molecules

Horwitz Matthew, Carrboro NC

Investigators

Abstract

The medicinal drugs that millions of people take every day contain bioactive molecules that are generally derived from natural products. The efficient construction of natural products and drug-like molecules necessitates high yielding and selective chemical reactions. Such reactions are enabled by the design and experimental development of new catalysts. This project will explore a family of catalysts developed in the host lab in systems that are familiar to the American collaborators. Under the guidance of Professor Xiaoming Feng at Sichuan University in Chengdu, China, the EAPSI fellow will utilize the new catalysts to study new types of reactivity and to apply these new methods in the synthesis of important targets. This investigation is expected to facilitate new reaction development that may open the door to new natural products and new medicines. This project aims to apply novel organocatalyts and transition metal-catalysts in new dynamic reaction manifolds. The primary activity that this project involves is running new kinds of chemical reactions. Using chiral guanidine systems as organocatalysts and N,N?-dioxide complexes as transition metal catalysts, this project will explore addition reactions into a- and b-keto esters. The resulting a- and b-hydroxy esters have been shown to have useful biological activity that merits their synthesis. Model nucleophiles are likely to include azlactone and pyrazolones, which are proposed for the efficient construction of three contiguous stereocenters. Using these substrates to study the Dynamic Kinetic Resolution (DKR) phenomenon, new building blocks for biologically important molecules will be generated. This NSF EAPSI award is funded in collaboration with the Chinese Ministry of Science and Technology.