School of Pharmaceutical Sciences, MOE Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology, Tsinghua University, Beijing 100084, China.
Chinese Institutes for Medical Research, Beijing 100069, China.
Org Lett. 2024 Jan 12;26(1):370-375. doi: 10.1021/acs.orglett.3c04038. Epub 2024 Jan 3.
Carolacton, a naturally occurring MTHFD1 inhibitor, exhibits potent inhibitory activity against various RNA viruses including SARS-CoV-2. Herein, we present a concise total synthesis of carolacton, featuring the Krische allylation, Marshall coupling, NHK coupling, and RCM reaction as key elements. Additionally, we have synthesized three simplified carolacton analogues, one of which, namely, 14-demethyl-carolacton, exhibited notable antiviral activity. The present work paves the way for further exploration of the therapeutic potential of carolacton and its analogues.
卡罗他汀是一种天然存在的 MTHFD1 抑制剂，对包括 SARS-CoV-2 在内的多种 RNA 病毒具有很强的抑制活性。在此，我们呈现了卡罗他汀的简洁全合成，关键步骤包括 Krische 烯丙基化、Marshall 偶联、NHK 偶联和 RCM 反应。此外，我们还合成了三个卡罗他汀类似物，其中一个，即 14-去甲基卡罗他汀，表现出显著的抗病毒活性。本工作为进一步探索卡罗他汀及其类似物的治疗潜力铺平了道路。
