2. Academic Validation
  3. Total Synthesis and SARS-CoV-2 3CLpro Inhibition Activities of (±)-Tuaimenal A and Its Derivatives

Total Synthesis and SARS-CoV-2 3CLpro Inhibition Activities of (±)-Tuaimenal A and Its Derivatives

  • J Nat Prod. 2025 Jun 27;88(6):1349-1359. doi: 10.1021/acs.jnatprod.5c00251.
Zeyu Tao 1,  Jichen Guan 1,  Guangyan Zhang 1,  Junyi Liu 1,  Xuan Pan 1,  Fangfang Lai 1,  Zhanzhu Liu 1
Affiliations

Affiliation

  • 1 State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100050, P. R. China.
PMID: 40388815 DOI: 10.1021/acs.jnatprod.5c00251
Abstract

The first total synthesis of (±)-tuaimenal A was achieved in six steps starting from sesamol, with an overall yield of 26.4%. The key transformation was a tandem pyridine-catalyzed condensation/6π-electrocyclization sequence, which efficiently constructed the 2H-benzopyran core. Chiral resolution of the racemate was accomplished by using Boc-d-Phe-OH as a chiral auxiliary. Enzymatic inhibition assays revealed that both (+)-tuaimenal A and its enantiomer exhibited comparable inhibitory activity against SARS-CoV-2 3CLpro (the viral main protease). Furthermore, 20 analogues were synthesized, and the preliminary structure-activity relationship (SAR) was discussed.

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