Development of new radical chemistry-based strategies for the construction of densely functionalized organic molecules

生物活性天然产物往往具有独特的化学结构和密集的功能，是一种有用的药用资源。作者一直致力于合成自由基化学，这将彻底改变提供获得这类有吸引力的分子的途径的策略。在本研究中，我们成功地设计了与sp3碳-氢(Sp3c-H)转化相关的新的自由基反应(叔胺的光化学Sp3c-H氨甲酰化反应)和铁(II)催化的N-苯磺酰氧基氨基甲酸酯的氨卤化反应，并完成了基于自由基化学的生物活性天然产物的全合成，包括红藻氨酸、铂和琼脂菌素A。此外，我们还开发了一种新的不对称合成方法，该方法利用远程立体诱导，可以方便地构建含有四元立体中心的碳环构筑块。通过上述全合成方法制备的铂菌素的生物学评价，使作者能够评价其对耐多药结核分枝杆菌的显著抑制活性，为抗结核药物的开发增添了新的维度。

Bioactive natural products often possess unique chemical structures with dense functionalities, serving as a useful medicinal resource. The authors have been engaged in synthetic radical chemistry that would revolutionize strategies for providing access to this class of attractive molecules. In the present study, we succeeded in devising new radical reactions associated with sp3carbon-hydrogen (sp3C-H) transformation (photochemical sp3C-H carbamoylation of tertiary amines) and iron(II)-catalyzed aminohalogenation reactions of N-tosyloxycarbamates, and accomplished radical chemistry-based total syntheses of bioactive natural products including kainic acid, platencin, and agelastatin A. Furthermore, we developed a novel means for asymmetric synthesis, which employsremote stereoinduction that allows facile construction of carbocyclic building blocks bearing quaternary stereocenters. The biological evaluation of platencin prepared by the above-mentioned total synthesishas allowed the authors to assess its significant inhibitory activity against multi-drug-resistant Mycobacterium tuberculosis, adding a new dimension to the development of antitubercular agents.