Department of Chemistry, University of Chicago, Chicago, Illinois 60607, USA.
J Org Chem. 2013 Sep 6;78(17):8645-54. doi: 10.1021/jo401262v. Epub 2013 Aug 27.
We have developed a synthetic strategy that mimics the diversity-generating power of monoterpenoid indole alkaloid biosynthesis. Our general approach goes beyond diversification of a single natural product-like substructure and enables production of a highly diverse collection of small molecules. The reaction sequence begins with rapid and highly modular assembly of the tetracyclic indoloquinolizidine core, which can be chemoselectively processed into several additional skeletally diverse structural frameworks. The general utility of this approach was demonstrated by parallel synthesis of two representative chemical libraries containing 847 compounds with favorable physicochemical properties to enable its subsequent broad pharmacological evaluation.
我们开发了一种模拟单萜吲哚生物碱生物合成多样性生成能力的合成策略。我们的一般方法不仅可以对单个类似天然产物的亚结构进行多样化，还可以生产出高度多样化的小分子集合。反应序列首先快速且高度模块化地构建四环吲哚喹啉啶核心，然后可以选择性地对其进行化学处理，形成几种骨架多样化的结构框架。该方法的通用性通过平行合成两个包含 847 种具有有利物理化学性质的化合物的代表性化学文库得到了证明，这使得能够对其进行广泛的药理学评估。
