Department of Chemistry, Southern University of Science and Technology, Shenzhen Grubbs Institute, Shenzhen, Guangdong, China.
Angew Chem Int Ed Engl. 2018 Mar 19;57(13):3386-3390. doi: 10.1002/anie.201800167. Epub 2018 Feb 15.
A nearly-30-year-old unanswered synthetic puzzle, astellatol, has been solved in an enantiospecific manner. The highly congested pentacyclic skeleton of this rare sesterterpenoid, which possesses a unique bicyclo[4.1.1]octane motif, ten stereocenters, a cyclobutane that contains two quaternary centers, an exo-methylene group, and a sterically encumbered isopropyl trans-hydrindane motif, makes astellatol arguably one of the most challenging targets for sesterterpenoid synthesis. An intramolecular Pauson-Khand reaction was exploited to construct the right-hand side scaffold of this sesterterpenoid. An unprecedented reductive radical 1,6-addition, mediated by SmI , forged the cyclobutane motif. Last, a strategic oxidation/reduction step provided not only the decisive solution for the remarkably challenging late-stage transformations, but also a highly valuable unravelling of the notorious issue of trans-hydrindane synthesis. Importantly, the synthesis of astellatol showcases a rapid, scalable strategy to access diverse complex isopropyl trans-hydrindane sesterterpenoids.
一种近 30 年未解的人工合成难题化合物——astellatol，现已以对映选择性的方式被破解。这种罕见的倍半萜类化合物具有独特的双环[4.1.1]辛烷骨架，十个手性中心，一个包含两个季碳原子的环丁烷，一个烯丙基，一个空间位阻较大的异丙基反氢茚烷骨架，使得 astellatol 成为倍半萜合成中最具挑战性的目标之一。该研究利用分子内 Pauson-Khand 反应构建了这种倍半萜的右手侧骨架。前所未有的 SmI 介导的还原自由基 1,6-加成形成了环丁烷骨架。最后，一个策略性的氧化/还原步骤不仅为极具挑战性的后期转化提供了决定性的解决方案，还为臭名昭著的反氢茚烷合成问题提供了一个极具价值的解决方法。重要的是，astellatol 的合成展示了一种快速、可扩展的策略，可以获得多种复杂的异丙基反氢茚烷倍半萜。
