In this EAGER project funded by the Chemical Synthesis Program of the Chemistry Division, Professor Lin Pu of the Department of Chemistry at University of Virginia will explore the development of peptide nucleic acids (PNAs)-based novel double helical catalysts for asymmetric catalysis. In comparison with the catalysts currently developed for asymmetric catalysis, the proposed PNA-based double helical catalysts could have several advantages. For example, the PNA-based duplexes could amplify the chiral information of the incorporated catalytic site to generate the macromolecular double helical structure which could provide rigid, stable, and well-defined helical cavities for efficient chiral induction. In addition, unlike the use of DNAs, using the synthetic PNAs makes both helical configurations readily available for the asymmetric synthesis of both enantiomers of a chiral molecule. These macromolecular catalysts can also be easily recovered by filtration (heterogeneous) or membrane filtration (homogeneous). The proposed work on PNAs will utilize the technology developed in chemical biology for the discovery of new chiral catalysts for asymmetric synthesis.
Successful development of the project will have an impact on any area of activity in which the synthesis of molecules is needed, such as the pharmaceutical, chemical, agricultural industry, and the biological and chemical research activities. Graduate students and undergraduate students of diverse backgrounds will be recruited to conduct the research described in this project. Thus, this project will provide extensive education and training for these researchers in areas such as organic synthesis, catalysis, chiral chemistry and chemical biology. They will learn many laboratory skills that are useful for their future employment. After the training through this project, the students can become new innovators and professional researchers to further benefit the society.
This project aims at developing new catalysts for asymmetric synthesis. We have incorporated chiral amino acid units into PNA oligomers. The duplexes of these PNA oligomers were prepared and their use in asymmetric reactions has been investigated. Highly enantioselective reactions of aldehydes with 1,3-enynes and other alkynes have also been developed by using the 1,1’-binaphthyl-based chiral catalyst systems. This method allows the synthesis of structurally diverse functional propargylic alcohols with high enantiomeric purity. Using the optically active propargylic alcohol-based trienynes, we have discovered a novel domino Pauson-Khand/[4+2] cyclization process to make molecules containing four fused rings with a quaternary chiral carbon core in one step. High chemoselectivity and stereoselectivity have been achieved in this process. Previously, molecules of such structures are difficult to prepare. Our new strategy could allow efficient construction of multicyclic organic molecules of biological and pharmaceutical significances. We have also discovered a diastereoselective [4+1] cycloaddition of alkenyl propargyl acetate with CO to generate highly functionalized cyclopentenones that are useful in organic synthesis. These results have been published in major chemistry journals. Under the direction of the PI, this project has trained a number of graduate and undergraduate students. Several of the graduate students have graduated and are working in either chemical industry or university. Among the undergraduate students, some have become graduate students in chemistry departments of major universities; some are going to medical school; and a few of them are female students. Thus, this project has educated people who will make diverse contributions to the society.
