This project addresses the design and exploitation of peptide architectures and multifunctional catalysts that mediate stereoselective reactions. Catalysts that incorporate functional groups within the well-defined architecture afforded by small peptides will be synthesized. In addition to mechanism-based design, systematic diversity-based approaches will be taken to catalyst discovery and optimization. With an overall focus on enantioselective C-C bond formation reactions, the goals of this project include the discovery of new peptide-based catalysts for enantioselective umpolung catalysis through the generation of formal acyl anion intermediates; the expansion of the cocatalysis concept (involving distinct peptide and amino acid catalytic partners) in the context of the Morita-Baylis-Hillman reaction and its relatives; and the discovery of novel enantioselective reactions of allenes based on a newly discovered amine-catalyzed allenoate-enone coupling. These studies will bring the peptide-based catalysts into the area of axial chirality stereocontrol.
With this award, the Organic and Macromolecular Chemistry Program is supporting the research of Dr. Scott J. Miller of the Department of Chemistry at Boston College. The field of chemical synthesis stands poised to make enormous contributions to the identification of new pharmaceuticals and in the preparation of novel materials. The discovery of highly efficient reactions that generate novel structures will play a critical role in these endeavors. This project is directed at the discovery of new catalysts that will mediate chemical reactions with high activity and efficiency, and in an environmentally benign fashion. Professor Miller and his students utilize many of the same principles that enzymes use in achieving efficient catalysis, but do so with a fraction of the molecular complexity. The work is conducted in an environment that is collaborative at multiple levels of the educational ladder, including the involvement of undergraduate students from primarily undergraduate institutions.
