重庆大学张敏团队报道了裂殖甘氨酸生物碱的不对称全合成。相关研究成果于2021年11月19日发表于国际一流学术期刊《美国化学会杂志》。

描述了四种裂殖甘氨酸生物碱的简明、集体和不对称全合成，其特征是具有“盘盖”状的六环核心支架，具有多达六个连续立体中心，包括两个四元立体中心。

该文提出了一种环丙醇在吲哚环C2上脱芳环化的新方法，以建立含酮基裂殖核的ABCF环系统。另一个关键的骨架构建反应，Heck/羰基内酰胺化级联反应，确保了六环裂唑烷核的快速组装和烯烃基团的同时安装。通过对这两个反应的战略性利用和功能化裂殖酸核心的后期多样化，以色胺为原料分11-12步完成了（+）-裂殖酸、（+）-3-oxo-14α、15α-环氧裂殖酸和（+）-α-裂殖酸的首次不对称全合成以及（+）-链霉素的全合成。

附：英文原文

Title: Asymmetric Total Syntheses of Schizozygane Alkaloids

Author: Wenqiang Zhou, Tao Zhou, Mengxing Tian, Yan Jiang, Jiaojiao Yang, Shuai Lei, Qi Wang, Chongzhou Zhang, Hanyue Qiu, Ling He, Zhen Wang, Jun Deng, Min Zhang

Issue&Volume: November 19, 2021

Abstract: The concise, collective, and asymmetric total syntheses of four schizozygane alkaloids, which feature a “Pan lid”-like hexacyclic core scaffold bearing up to six continuous stereocenters, including two quaternary ones, are described. A new method of dearomative cyclization of cyclopropanol onto the indole ring at C2 was developed to build the ABCF ring system of the schizozygane core with a ketone group. Another key skeleton-building reaction, the Heck/carbonylative lactamization cascade, ensured the rapid assembly of the hexacyclic schizozygane core and concurrent installation of an alkene group. By strategic use of these two reactions and through late-stage diversifications of the functionalized schizozygane core, the first and asymmetric total syntheses of (+)-schizozygine, (+)-3-oxo-14α,15α-epoxyschizozygine, and (+)-α-schizozygol and the total synthesis of (+)-strempeliopine have been accomplished in 11–12 steps from tryptamines.

DOI: 10.1021/jacs.1c10279

Source: https://pubs.acs.org/doi/10.1021/jacs.1c10279