Total Synthesis of Carolacton and Demethylcarolactons with Potent Antiviral Activity
Haoyu Zhang1, Bingsong Li1, Hongzhi Yang1
1School of Pharmaceutical Sciences, MOE Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology, Tsinghua University, Beijing 100084, China.
Abstract:
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.
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