Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California-San Diego, La Jolla, California 92093-0204, USA.
Org Lett. 2013 Mar 1;15(5):988-91. doi: 10.1021/ol303374e. Epub 2013 Feb 13.
Cultivation of an obligate marine Streptomyces strain has provided the cytotoxic natural product chlorizidine A. X-ray crystallographic analysis revealed that the metabolite is composed of a chlorinated 2,3-dihydropyrrolizine ring attached to a chlorinated 5H-pyrrolo[2,1-a]isoindol-5-one. The carbon stereocenter in the dihydropyrrolizine is S-configured. Remarkably, the 5H-pyrrolo[2,1-a]isoindol-5-one moiety has no precedence in the field of natural products. The presence of this ring system, which was demonstrated to undergo facile nucleophilic substitution reactions at the activated carbonyl group, is essential to the molecule's cytotoxicity against HCT-116 human colon cancer cells.
一株海洋放线菌的培养为我们提供了具有细胞毒性的天然产物——chlorizidine A。X 射线晶体学分析表明,该代谢产物由一个氯化的 2,3-二氢吡咯里嗪环连接到一个氯化的 5H-吡咯并[2,1-a]异吲哚-5-酮上。二氢吡咯里嗪中的碳立体中心为 S 构型。值得注意的是,5H-吡咯并[2,1-a]异吲哚-5-酮部分在天然产物领域中没有先例。该环系的存在对于该分子对 HCT-116 人结肠癌细胞的细胞毒性至关重要,因为它可以在活化的羰基处进行容易的亲核取代反应。