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

IF 1.1 4区 化学 Q3 CHEMISTRY, MULTIDISCIPLINARY
Xina Wang, Julia Vu, Charissa Luk, Edward Njoo
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引用次数: 1

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.
台式19F核磁共振波谱使动力学研究和优化合成卡莫弗
Carmofur是一种5-氟尿嘧啶衍生物,最初是作为治疗结直肠癌的抗肿瘤药物开发的。通过药物重新利用的努力,它已被确定为SARS-CoV-2主要蛋白酶(Mpro)的有效共价抑制剂,使其成为一种有前景的治疗COVID-19的药物。然而,以前的合成方法存在产率低或反应时间长的问题。在本研究中,台式19F核磁共振波谱(NMR)通过提供动力学洞察,实现了对carmofur合成的实时定量监测和表征。此外,它的质子锁功能不再需要使用氘化溶剂,并且使我们的化合物合成方便,快速扩展。在此,我们介绍了台式19F NMR作为优化carmofur合成的有效方法及其在相关5-FU类似物合成中的应用前景。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Canadian Journal of Chemistry
Canadian Journal of Chemistry 化学-化学综合
CiteScore
1.90
自引率
9.10%
发文量
99
审稿时长
1 months
期刊介绍: Published since 1929, the Canadian Journal of Chemistry reports current research findings in all branches of chemistry. It includes the traditional areas of analytical, inorganic, organic, and physical-theoretical chemistry and newer interdisciplinary areas such as materials science, spectroscopy, chemical physics, and biological, medicinal and environmental chemistry. Articles describing original research are welcomed.
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