（±）-Tuaimenal A及其衍生物的总合成及其对sars - cov - 23clpro的抑制活性

IF 3.3 2区生物学 Q2 CHEMISTRY, MEDICINAL

Journal of Natural Products Pub Date : 2025-05-19 DOI:10.1021/acs.jnatprod.5c00251

Zeyu Tao, Jichen Guan, Guangyan Zhang, Junyi Liu, Xuan Pan, Fangfang Lai, Zhanzhu Liu

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引用次数: 0

摘要

以芝麻为原料，经6步合成了（±）-乙酰氨基酚A，总收率为26.4%。关键转化是串联吡啶催化的缩合/6π电环化序列，有效地构建了2h -苯并吡喃核。用boc -d- ph - oh作为手性助剂，完成了外消旋体的手性拆分。酶促抑制实验显示(+)-tuaimenal A及其对映体对sars - cov - 23clpro（病毒主要蛋白酶）具有相当的抑制活性。合成了20个类似物，并初步探讨了它们的构效关系。

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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 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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来源期刊

Journal of Natural Products 生物-药学

CiteScore

9.10

自引率

5.90%

发文量

294

审稿时长

2.3 months

期刊介绍： The Journal of Natural Products invites and publishes papers that make substantial and scholarly contributions to the area of natural products research. Contributions may relate to the chemistry and/or biochemistry of naturally occurring compounds or the biology of living systems from which they are obtained. Specifically, there may be articles that describe secondary metabolites of microorganisms, including antibiotics and mycotoxins; physiologically active compounds from terrestrial and marine plants and animals; biochemical studies, including biosynthesis and microbiological transformations; fermentation and plant tissue culture; the isolation, structure elucidation, and chemical synthesis of novel compounds from nature; and the pharmacology of compounds of natural origin. When new compounds are reported, manuscripts describing their biological activity are much preferred. Specifically, there may be articles that describe secondary metabolites of microorganisms, including antibiotics and mycotoxins; physiologically active compounds from terrestrial and marine plants and animals; biochemical studies, including biosynthesis and microbiological transformations; fermentation and plant tissue culture; the isolation, structure elucidation, and chemical synthesis of novel compounds from nature; and the pharmacology of compounds of natural origin.