Benchtop 19F nuclear magnetic resonance spectroscopy enabled kinetic studies and optimization of the synthesis of carmofur

12 October 2022, Version 1
This content is a preprint and has not undergone peer review at the time of posting.

Abstract

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.

Keywords

Carmofur
19F NMR Spectroscopy
Reaction Monitoring
Benchtop NMR Spectroscopy

Supplementary materials

Title
Description
Actions
Title
Supplementary Material for Benchtop 19F nuclear magnetic resonance spectroscopy enabled kinetic studies and optimization of the synthesis of carmofur
Description
Supplementary Material for Benchtop 19F nuclear magnetic resonance spectroscopy enabled kinetic studies and optimization of the synthesis of carmofur Includes characterization data, general optimization and scaleup procedures, etc.
Actions

Comments

Comments are not moderated before they are posted, but they can be removed by the site moderators if they are found to be in contravention of our Commenting Policy [opens in a new tab] - please read this policy before you post. Comments should be used for scholarly discussion of the content in question. You can find more information about how to use the commenting feature here [opens in a new tab] .
This site is protected by reCAPTCHA and the Google Privacy Policy [opens in a new tab] and Terms of Service [opens in a new tab] apply.