Photoelectrocyclizations to Anti-Inflammatory Natural Products

With the support of the Division of Chemistry, Professor Jon Rainier of the University of Utah is studying reactions that use light to form polycyclic substrates from relatively simple starting materials. That the types of molecules being synthesized using these reactions are useful in fields ranging from pharmaceuticals and medicine to agriculture, chemicals, and materials makes these studies relevant and timely. In addition to leading to the rapid buildup of complexity, these studies are expected to provide fundamental information about the impact of substitution and three-dimensional structural motifs on reactions that use light as a reagent. In addition to the reaction chemistry, this project will contribute to the development and training a diverse group of graduate and undergraduate students, including community college students, as researchers to become members of the future scientific workforce. In terms of outreach, the Utah team is developing a literature/book club that is helping individuals from a variety of backgrounds to discuss current issues with the ultimate goal of developing a more inclusive and diverse workforce. The overarching goal of this project is to utilize light to convert relatively simple starting materials into complex, optically active products that share core architectures with bioactive natural products like those that exist in the ansalactam and ergoline families. At a fundamental level, the proposed studies are uncovering photochemical phenomena that are only observed in more complex systems. For example, we are examining the effect of substitution on excited states and how this relates to the outcomes from electrocyclization reactions, the influence of ground state conformations on the regioselectivity of excited state reactions as seen in [2+2] photocycloaddition reactions, and the use and optimization of auxiliaries and chiral catalysts in diastereo- and enantioselective cycloaddition and electrocyclization reactions. Finally, the reactions under study are photo-initiated cycloaddition and electrocyclization reactions of readily available starting materials, that, by design, are atom-economical and minimize byproduct formation. 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.