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

点击翻译按钮获取中文摘要

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.