CAS Key Laboratory of Synthetic Chemistry of Natural Substances, Center for Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, China.
J Am Chem Soc. 2021 Aug 25;143(33):13016-13021. doi: 10.1021/jacs.1c07511. Epub 2021 Aug 16.
Herein we report the first total synthesis of polychlorinated steroids clionastatins A and B, which was accomplished asymmetrically by means of a convergent, radical fragment coupling approach. Key features of the synthesis include an Ireland-Claisen rearrangement to introduce the C5 stereocenter (which was ultimately transferred to the C10 quaternary stereocenter of the clionastatins via a traceless stereochemical relay), a regioselective acyl radical conjugate addition to join the two fragments, an intramolecular Heck reaction to install the C10 quaternary stereocenter, and a diastereoselective olefin dichlorination to establish the synthetically challenging pseudoequatorial dichlorides. This work also enabled us to determine that the true structures of clionastatins A and B are in fact C14 epimers of the originally proposed structures.
在此，我们报告了聚氯甾体 clionastatins A 和 B 的首次全合成，该合成通过一种会聚的、自由基片段偶联方法进行不对称合成。合成的关键特征包括 Ireland-Claisen 重排以引入 C5 立体中心（该立体中心最终通过无痕迹立体化学接力转移到 clionastatins 的 C10 季碳立体中心）、区域选择性酰基自由基共轭加成连接两个片段、分子内 Heck 反应以安装 C10 季碳立体中心以及立体选择性烯烃二氯化以建立具有挑战性的假赤道二氯化物。这项工作还使我们能够确定 clionastatins A 和 B 的真实结构实际上是最初提出的结构的 C14 差向异构体。
