Total Synthesis and SARS-CoV-2 3CLpro Inhibition Activities of (±)-Tuaimenal A and Its Derivatives
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 2<i>H</i>-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.
Authors
- Fangfang Lai (ORCID: https://orcid.org/0000-0003-1696-6208)
- Guangyan Zhang (ORCID: https://orcid.org/0000-0003-1513-0003)
- Xuan Pan (ORCID: https://orcid.org/0000-0002-8308-8495)
- Zhanzhu Liu (ORCID: https://orcid.org/0000-0002-2181-5626)
- Zeyu Tao (ORCID: https://orcid.org/0009-0005-5053-9201)
- Junyi Liu (ORCID: https://orcid.org/0000-0001-5702-3519)
- Jichen Guan
Institutions
- Academy of Medical Sciences (GB)
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- Peking Union Medical College Hospital (CN)
- Shanghai Institute of Materia Medica (CN)
Publication Details
- Journal
- Journal of Natural Products
- Published
- 2025-05-19
- DOI
- https://doi.org/10.1021/acs.jnatprod.5c00251
- Primary Topic
- Ginger and Zingiberaceae research
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Chinese Academy of Medical Sciences