Complexity-building Approaches in Photoassisted Synthesis of Heterocycles

点击翻译按钮获取中文摘要

With this award, the Chemical Synthesis Program of the NSF Division of Chemistry is supporting the research of Professor Andrei Kutateladze, Department of Chemistry and Biochemistry at the University of Denver. The research is focused on developing new methods for synthesis of complex organic molecules containing multiple ring substructures. This will be done using photons of light as an environmentally abundant and safe reagent and the approach achieves structural complexity with a minimal number of experimental steps. Besides the fundamental importance of learning about interactions of light and matter in the context of synthetic chemistry, the targeted complex polyheterocycles (i.e. molecules which contain nitrogen, sulfur, or oxygen atoms as a part of a ring) are intentionally designed to resemble alkaloids (a class of naturally occurring organic bases) and other biologically active natural products that may potentially possess useful therapeutic properties. Importantly, this award supports research experiences for undergraduate and graduate students, especially those from historically underrepresented groups in science, provided them with useful skill sets in modern organic chemistry and photochemistry; excellent preparation for career paths in either academia or industry.This research expands the toolbox for excited state intramolecular proton transfer (ESIPT)-based synthetic photochemistry with several new photo-assisted synthetic reaction cascades. The photo-induced reaction cascades allow the experimentalist to achieve large step-normalized complexity increases and rapidly assemble novel fused polyheterocyclic molecular architectures. Additional growth of complexity is realized through post-photochemical transformations, such as multi-step carbocationic cascades and rearrangements. Investigations of reaction mechanisms and stereochemistry of these ESIPT-triggered cascades help achieve control of stereochemical and regiochemical outcomes. This experimental work is augmented by computation, especially to facilitate solution structure elucidation of the complex polyheterocyclic products by NMR. The new integrated DU8+ method for fast and accurate calculation of NMR parameters includes PCM models and solvent-specific parameterization schemes. This computational tool is are critical for success of this project, but also has broader implications for structure elucidation of complex synthetic and natural product target molecules. Additionally, this research provides hands-on laboratory training for graduate and undergraduate students, and research associates, especially those from historically underrepresented groups in science.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.