Скачать или смотреть Benchtop 19F Nuclear Magnetic Resonance Spectroscopy Enabled Kinetic Studies of Carmofur

The ASDRP Summer 2022 Semester Research Symposium and Expo showcases some of the original scientific findings of 625+ high school students, who conducted research across 80+ projects in a wide array of STEM fields. Students come from throughout Bay Area, across the U.S., and internationally! The Symposium features students presenting the research they completed throughout the summer during their participation in ASDRP.

Xina Wang, Amber Lu, Kavya Pandrangi, Lexi Xu, Breanna Lu, Theodore Khow, and Erika Yu present their project "Benchtop 19F Nuclear Magnetic Resonance Spectroscopy Enabled Kinetic Studies and Reaction Optimization of the Synthesis of Carmofur and Related 5-fluorouracil Analogs" at the Summer 2022 Virtual Blitz Talks Symposium and Expo.

Abstract:
Carmofur, a prodrug derivative of 5-fluorouracil (5-FU), was initially developed as an antineoplastic agent used in the treatment of colorectal and other cancers by acid ceramide-induced apoptosis. Recent drug repurposing efforts have identified carmofur as a covalent inhibitor of the SARS-CoV-2 main protease. This SARS-CoV-2 main protease (Mpro) plays an essential role in the processing of the polyproteins that are translated from the viral RNA, therefore making it an attractive drug target for the treatment of COVID-19. Here, we present the in silico evaluation and synthesis of carmofur and a library of related 5-fluorouracil analogs with aliphatic, amino acid, and aromatic fragments against mutations in Mpro. Furthermore, carmofur’s 5-FU head serves as a spectroscopic handle for benchtop 19F nuclear magnetic resonance spectroscopy (NMR). Recent advances in benchtop NMR has facilitated real-time monitoring, characterization, and quantification of chemical entities without the use of financially prohibitive deuterated solvents, and provides the opportunity to rapidly and quantitatively optimize reaction conditions that conventional reaction tracking methods cannot produce. Here, we implement benchtop 19F NMR as a practical analytical tool to track the reaction kinetics of 5-FU with various isocyanates, and optimize reaction conditions to synthesize carmofur and its analogs on-scale for future in vivo biological testing.

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