Graduate School of Pharmaceutical Sciences, Meiji Pharmaceutical University , 2-522-1 Noshio, Kiyose, Tokyo 204-8588, Japan.
Department of Chemistry, Colorado State University , Fort Collins, Colorado 80523, United States.
J Org Chem. 2016 May 20;81(10):4039-47. doi: 10.1021/acs.joc.6b00327. Epub 2016 May 3.
A stereoselective total synthesis of (-)-Renieramycin T (1t) from a key tetrahydroisoquinoline intermediate previously utilized in our formal total synthesis of Ecteinascidin 743 is described. The synthesis features a concise approach for construction of the pentacyclic framework using a Pictet-Spengler cyclization of bromo-substituted carbinolamine 17, which obviates the regioselectivity problem of the Pictet-Spengler cyclization. The results of cytotoxicity studies are also presented.
本文描述了从先前用于埃替拉宁 743 全合成的关键四氢异喹啉中间体出发,对(-)-雷尼霉素 T(1t)进行立体选择性全合成的方法。该合成方法采用溴取代的仲醇胺 17 的Pictet-Spengler 环化反应,构建五环骨架,简洁高效,同时避免了Pictet-Spengler 环化的区域选择性问题。本文还介绍了细胞毒性研究的结果。