Point-to-Axial Chirality Transfer: Enabling Stereochemica Determinations and Enantioselective Reactions

Michigan State University, East Lansing MI

Investigators

Abstract

In this project, funded by the Chemical Structure, Dynamics & Mechanisms-B Program of the Chemistry Division, Professor Babak Borhan of the Chemistry Department at Michigan State University (MSU) is developing new methodologies to rapidly identify the chirality of organic molecules. Many molecules have ‘chiral centers’, the identity of which is critical to their physical characteristics and biological function. Two molecules that are mirror images of each other are referred to as enantiomers. Enantiomers can have dramatically different biological activities; for example, (+)-carvone is terpenoid natural product that is the essence of caraway, whereas its mirror image, (-)-carvone is the essence of spearmint. These completely different flavors arise from diastereomeric interactions with the chiral proteins associated with the sensing of taste. This, and many other important examples, show the need for accurate and reliable methods to identify chiralities of molecules. This is the central theme of the funded proposal. Professor Borhan's group has also been the leader at MSU for the past 24 years in organizing and leading Project SEED, an 8– 10-week summer program funded in part through the American Chemical Society and various organizations at MSU, to support research of high school students from financially disadvantaged families. This effort will continue during the next funding period. The project entails designing and synthesizing supramolecular assemblies to function as sensors for detecting molecular structural asymmetry. The principal objectives of this research are to develop straightforward, rapid, efficient, and unambiguous methods for determining the absolute stereochemistry of chiral organic molecules. Many of these molecules serve as intermediates in the synthesis of bioactive compounds or are newly discovered pharmacologically active metabolites. Circular dichroism (CD) will serve as the primary tool for observing the interactions between the chiral compounds and receptors in host-guest interactions. The project focuses on various functional groups, including chiral epoxides, alcohols, silanols, boranes, alkenes, allenes, alkynes, and alkyl arenes. Moreover, the introduction of 'molecular clips' as a novel host system will be explored and analyzed. Additionally, the MSU team plans to exploit the intrinsic helicity of these supramolecular complexes, induced by their interactions with bound asymmetric guest molecules, for applications in asymmetric catalysis, for example, in asymmetric transfer hydrogenation and in asymmetric excited state proton transfer. 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.