Key Laboratory of Drug Targeting and Drug Delivery Systems of the Ministry of Education, West China School of Pharmacy and State Key Laboratory of Biotherapy, Sichuan University, Chengdu, 610041, P.R. China.
Angew Chem Int Ed Engl. 2017 Mar 20;56(13):3703-3707. doi: 10.1002/anie.201700831. Epub 2017 Feb 23.
The asymmetric total syntheses of a group of structurally complex Kopsia alkaloids, (-)-kopsine, (-)-isokopsine, (+)-methyl chanofruticosinate, (-)-fruticosine, and (-)-kopsanone, has been achieved. The key strategies for the construction of the molecular complexity in the targets included an asymmetric Tsuji-Trost rearrangement to set the first quaternary carbon center at C20, an intramolecular cyclopropanation by diazo decomposition to install the second and third quaternary carbon centers at C2 and C7, respectively, and a SmI -promoted acyloin condensation to assemble the isokopsine core. A radical decarboxylation of an isokopsine-type intermediate results in a thermodynamic partial rearrangement to give N-decarbomethoxyisokopsine and N-decarbomethoxykopsine, two key intermediates for the syntheses of Kopsia alkaloids with different subtype core structures.
一组结构复杂的黄皮树生物碱（-）-kopisine、（-）-异黄皮树碱、（+）-甲基蝉佛斯定酸盐、（-）-佛斯定碱和（-）-黄皮酮的不对称全合成已经实现。在目标分子复杂性构建的关键策略中，包括不对称的 Tsuji-Trost 重排以在 C20 处设置第一个季碳原子中心、通过重氮分解的分子内环丙烷化分别在 C2 和 C7 处安装第二个和第三个季碳原子中心、以及 SmI-促进的缩醛缩合以组装异黄皮树碱核心。异黄皮树碱型中间体的自由基脱羧导致热力学部分重排，生成 N-脱甲氧基异黄皮树碱和 N-脱甲氧基黄皮树碱，这是合成具有不同亚类型核心结构的黄皮树生物碱的两个关键中间体。
