Thuggacin A (1) is a 17-membered-ring-polyketide antibiotic compound with excellent antituberculosis activity. The total synthesis of thuggacin A has not yet been reported so far. Herein, we disclose our efforts toward the convergent total synthesis of thuggacin A. The key synthetic features include our own one-pot cascade thiazole formation, Evans syn-aldol, Mukaiyama asymmetric aldol reaction, organosilicon-promoted selective alkyne reduction, Shiina macrolactonization, and a nucleophilic ring-opening of epoxide with alkyne to assemble the main framework of thuggacin A. The enantioselective synthesis of trimethylsilyl ethoxymethyl (SEM) derived thuggacin A analogue 2 was achieved in 18 longest linear steps with 2.0% overall yield, and the bioassay of 2 exhibited moderate antituberculosis activity with minimum inhibitory concentration (MIC) of 320 μg/mL.

中文翻译：

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Thuggacin A 的全合成努力


Thuggacin A （1） 是一种 17 元环聚酮类抗生素化合物，具有优异的抗结核活性。到目前为止，尚未报道 thuggacin A 的全合成。在此，我们披露了我们为 thuggacin A 的趋同全合成所做的努力。主要合成特征包括我们自己的一锅级联噻唑形成、Evans syn-aldol、Mukaiyama 不对称羟醛反应、有机硅促进的选择性炔烃还原、椎骨大内酯化以及环氧化物与炔烃的亲核开环以组装 thuggacin A 的主要框架。三甲基硅烷基乙氧基甲基 （SEM） 衍生的 thuggacin A 类似物 2 的对映选择性合成在 18 个最长的线性步骤中实现，总产率为 2.0%，2 的生物测定表现出中等抗结核活性，最低抑菌浓度 （MIC） 为 320 μg/mL。