中国科学院昆明植物研究所Pema-Tenzin Puno团队报道了(−)‐Isoscopariusin A，一种天然存在的免疫抑制性甲二萜的结构解析和可扩展的化学合成。 相关研究成果发表在2021年2月23日出版的《德国应用化学》。

从帚状香茶菜的地上部分分离得到(−)‐Isoscopariusin A。化学合成和光谱分析证实了它是一种具有6/6/4三环碳骨架和7个连续立体中心的不对称的二萜化合物。以市售的（+）月桂内酯为原料，经过12个步骤得到了克级合成。利用钴催化的氢原子转移烯烃异构化反应制备三取代烯烃，该烯烃与相应酰胺原位生成的取代烯酮亚胺离子进行立体选择性[2+2]环加成反应。

环丁酮产品通过表面选择性同系物进一步细化为完全取代的环丁烷核，并分别通过镍催化的交叉电泳偶联和碳二亚胺介导的酯化反应来安装两个侧链。(−)‐Isoscopariusin A对T细胞增殖有选择性抑制作用。

附：英文原文

Title: (−)‐Isoscopariusin A, a Naturally Occurring Immunosuppressive Meroditerpenoid: Structure Elucidation and Scalable Chemical Synthesis

Author: Bing-Chao Yan, Min Zhou, Jian Li, Xiao-Nian Li, Shi-Jun He, Jian-Ping Zuo, Han-Dong Sun, Ang Li, Pema-Tenzin Puno

Issue&Volume: 2021-02-23

Abstract: ()‐Isoscopariusin A  was isolated from the aerial parts of  Isodon scoparius  . Chemical synthesis and spectroscopic analysis established its structure as an unsymmetrical meroditerpenoid bearing a sterically congested 6/6/4 tricyclic carbon skeleton with seven continuous stereocenters. A gram‐scale synthesis was achieved in 12 steps from commercially available (+)‐sclareolide. A cobalt catalyzed, hydrogen atom transfer‐based olefin isomerization was used to prepare a trisubstituted alkene, which underwent stereoselective [2 + 2] cycloaddition with a substituted keteniminium ion generated in situ from the corresponding amide. The cyclobutanone product was further elaborated into the fully substituted cyclobutane core through face‐selective homologation, and the two side chains were installed by using nickel‐catalyzed cross‐electrophile coupling and carbodiimide‐mediated esterification, respectively. ()‐Isoscopariusin A displayed  selective inhibition of T‐cell proliferation.

DOI: 10.1002/anie.202100288

Source: https://onlinelibrary.wiley.com/doi/10.1002/anie.202100288