Investigating Functional Peptides for Asymmetric Hypervalent Iodine Catalysis

Clemson University, Clemson SC

Investigators

Abstract

The Chemical Synthesis Program of the Chemistry Division supports the project by Professor Daniel Whitehead at Clemson University. His group is developing new catalysts that are capable of promoting selective chemical oxidation reactions. Oxidation reactions are essential synthetic tools because they increase the overall functionality of a molecule. Yet in spite of this importance, oxidation reactions that recognize different mirror images of molecules remain elusive. This is a problem because natural systems recognize specific mirror images of a molecule. Hence, the majority of new molecules forwarded as pharmaceuticals must be comprised of only one mirror image. Reactions that cannot operate in this context have limited utility. In this project, Professor Whitehead and his students are conducting oxidation reactions with activated iodine species. To do so in a manner that recognized the mirror images of a molecule, the activated iodine species are being urrounded by a peptide ligand that controls the three-dimensional environment around the reagent. Peptide ligands can be readily made with tremendous control of shape and functionality. Hence, their use provides an outstanding opportunity for discovery. In the effort being pursued, this synthetic work is combined with spectroscopy, X-Ray crystallography, and mechanistic studies in order to gain a better understanding of the factors that control selectivity in oxidation reactions. The project is contributing to the growing number of new methods for the synthesis of organic molecules with practical relevance to both the pharmaceutical and fine chemical industry. This project is well suited for the education of both undergraduate and graduate-level scientists. Professor Whitehead's group is well positioned to provide the highest level of education and training for students underrepresented in science by recruiting these individuals to participate in laboratory research related to the project. Outreach activities involving K-6 Montessori students and grade-school aged homeschoolers are also being pursued as part of the funded project. Enantioselective catalytic transformations mediated by hypervalent iodine reagents are relatively rare, despite several key advances in the last 10 years. These organocatalysts offer access to a wide variety of oxidative transformations of organic substrates while avoiding the use of expensive and toxic heavy-metal based catalysts. This project is building upon significant preliminary data in order to develop a new class of peptide-based chiral hypervalent iodine catalysts in order to address two key goals: 1) to understand the structural drivers governing the observed enantioselectivity of initial "hit" peptide catalysts for the asymmetric alpha-oxytosylation of ketones and oxidative lactonization of keto-acids; and 2) to investigate novel iodo-arene containing amino acids in peptide scaffolds, optimize newly discovered catalysts, and expand the substrate/transformation scope of this new class of catalysts. The work is training both graduate and undergraduate students in synthetic organic chemistry, spectroscopy, crystallography, and organic reaction mechanisms. Outreach efforts focus on facilitating science experiments with area Montessori and home-school students.