Department of Chemistry, Yale University, 225 Prospect Street, New Haven, Connecticut 06520-8107, United States.
Graduate School of Pharmaceutical Sciences, Chiba University, Chiba 260-8675, Japan.
J Am Chem Soc. 2023 Mar 1;145(8):4394-4399. doi: 10.1021/jacs.2c13584. Epub 2023 Feb 15.
Herein we report the first total synthesis of the indole diterpenoid natural product shearilicine by an 11-step sequence via a generalizable precursor to the highly oxidized subclass of indole diterpenoids. A native chiral auxiliary strategy was employed to access the target molecule in an enantiospecific fashion. The formation of the key carbazole substructure was achieved through a mild intramolecular Heck cyclization, wherein a computational study revealed noncovalent substrate-ligand and ligand-ligand interactions that promoted migratory insertion.
在此，我们通过 11 步序列首次全合成了吲哚二萜天然产物 shearilicine，该序列通过一个通用的前体合成了高度氧化的吲哚二萜类化合物亚类。采用天然手性辅基策略以对映选择性方式获得目标分子。关键咔唑亚结构的形成是通过温和的分子内 Heck 环化实现的，其中计算研究揭示了促进迁移插入的非共价底物-配体和配体-配体相互作用。
