Department of Chemistry , University of California , Berkeley , California 94720 , United States.
J Am Chem Soc. 2019 Feb 13;141(6):2233-2237. doi: 10.1021/jacs.8b13388. Epub 2019 Feb 4.
The first synthesis of a pentacyclic ambiguine (ambiguine P) is reported. The synthesis takes advantage of sequential alkylations of an indole core to rapidly construct the pentacyclic framework of the natural product. Key to the success of the synthesis was the use of a Nicholas reaction to alkylate at C2, crafting a fused seven-membered ring that is characteristic of the pentacyclic ambiguines, as well as the use of an amide-directed functionalization at C12 to set a requisite quaternary center. A versatile late-stage intermediate was prepared that may be applicable to the synthesis of the other pentacyclic ambiguines.
首次报道了五环稠合吖庚因（ambiguine P）的全合成。该合成利用吲哚核心的顺序烷基化反应，快速构建天然产物的五环骨架。合成的关键在于使用 Nicholas 反应在 C2 位烷基化，形成一个特征为五环稠合吖庚因的稠合七元环，以及使用酰胺定向官能团化在 C12 位构建必需的季碳原子。制备了一种多功能的晚期中间体，可能适用于其他五环稠合吖庚因的合成。
