Carmofur, a 5-fluorouracil derivative, was initially developed as an antineoplastic agent to treat colorectal cancer. Through drug repurposing efforts, it has been identified as a potent covalent inhibitor of the main protease of SARS-CoV-2 (Mpro), making it a promising therapeutic agent against COVID-19. However, previous synthetic procedures suffer from low yields, or long reaction times. In this study, benchtop 19F nuclear magnetic resonance spectroscopy (NMR) enables the real-time quantitative monitoring and characterization of the synthesis of carmofur by providing kinetic insight. Furthermore, its proton lock capabilities no longer require the use of deuterated solvents, and has enabled convenient, and rapidly scalable synthesis of our compound. Here, we present the application of benchtop 19F NMR as an efficient method for optimizing the synthesis of carmofur and its future application in the synthesis of related 5-FU analogs.
Protein dimerization often occurs in many biological systems as to provide structural and functional advantages. A tris(5‐iodoacetamido‐1,10‐phenanthroline)Ruthenium(II) complex was shown to promote the covalent dimerization of a P450 BM3 heme domain mutant containing a surface‐exposed nonnative single cysteine residue. The formation of homodimeric species was confirmed by protein gel electrophoresis, mass spectrometry and UV–Vis spectroscopy. The dimeric species could be separated from the monomer and aggregates by size‐exclusion chromatography. Docking simulation reveals a plausible structure with two proteins covalently conjugated to the inorganic compound.
Carmofur, a 5-fluorouracil derivative, was initially developed as an antineoplastic agent to treat colorectal cancer. Through drug repurposing efforts, it has been identified as a potent covalent inhibitor of the main protease of SARS-CoV-2 (Mpro), making it a promising therapeutic agent against COVID-19. However, previous synthetic procedures suffer from low yields, or long reaction times. In this study, benchtop 19F nuclear magnetic resonance spectroscopy (NMR) enables the real-time quantitative monitoring and characterization of the synthesis of carmofur by providing kinetic insight. Furthermore, its proton lock capabilities no longer require the use of deuterated solvents, and has enabled convenient, and rapidly scalable synthesis of our compound. Here, we present the application of benchtop 19F NMR as an efficient method for optimizing the synthesis of carmofur and its future application in the synthesis of related 5-FU analogs.
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