中国科学院长春应用化学研究所韩福社课题组提出了，催化不对称全合成(+)-Chamaecydin和(+)-Isochamaecydin及其立体异构体。相关论文于2025年1月9日发表于国际顶尖学术期刊《德国应用化学》杂志上。

研究者采用模块化方法首次催化不对称全合成了，天然存在的C30萜烯醌及其非天然立体异构体，其特征是存在前所未有的含螺[4.4]壬烷的6-6-6-5-5-3六环骨架。以手性磷酰胺催化2,2-二取代环己烷-1,3-二酮的对映选择性还原为基础，研究者建立了一条合成富集对映体的6-6双环片段的简捷路线。6-6环片段和5元环片段，通过金属-卤素交换/分子间加成反应完成并环统一。

随后，他们又通过Michael/aldol级联构建了中心6-5双环体系。这些战略转化的成功建立使得通过收敛方式，高效快速地构建螺环6-6-6-5-5五碳环核心成为可能。最后，通过适当安排反应顺序，包括异丙基加入、氧化态调整，和羰基导向的区域和立体选择性环丙化，在后期实现了天然存在的(+)-chamaecydin和(+)-Isochamaecydin，及其相应的1',5-'立体异构体的全合成。

附：英文原文

Title: Catalytic Asymmetric Total Synthesis of (+)-Chamaecydin and (+)-Isochamaecydin and their Stereoisomers

Author: Fu-She Han, Yuan-He Zhang, Le-Hua Deng, Dong-Xing Tan

Issue&Volume: 2025-01-09

Abstract: A modular approach was developed for the first catalytic asymmetric total syntheses of naturally occurring C30 terpene quinone methides and their non-natural stereoisomers, which feature the presence of an unprecedented spiro[4.4]nonane-containing 6-6-6-5-5-3 hexacyclic skeleton. Resting on a chiral phosphinamide-catalyzed enantioselective reduction of 2,2-disubstituted cyclohexane-1,3-dione, a concise route for the synthesis of enantioenriched 6-6 bicyclic fragment was developed. The 6-6 ring fragment and the five-membered ring fragment were unified via a metal-halogen exchange/intermolecular addition reaction. Subsequently, the central 6-5 bicyclic ring system was constructed through a Michael/aldol cascade. The successful establishment of these strategic transformations allowed for an efficient and rapid construction of spiroannulated 6-6-6-5-5 pentacarbocyclic core via a convergent manner. Finally, the total syntheses of naturally occurring (+)-chamaecydin and (+)-isochamaecydin and their corresponding 1’,5’-stereoisomers have been achieved divergently by appropriately orchestrating the reaction sequence including isopropyl incorporation, oxidation state adjustment, and carbonyl group-directed regio- and stereoselective cyclopropanation at a late stage.

DOI: 10.1002/anie.202423944

Source: https://onlinelibrary.wiley.com/doi/10.1002/anie.202423944