Department of Chemistry and Biochemistry, The University of Texas at Austin, Austin, Texas 78712, United States.
J Am Chem Soc. 2013 Sep 4;135(35):12984-6. doi: 10.1021/ja4070206. Epub 2013 Aug 23.
Actinophyllic acid is a biologically active indole alkaloid with a unique structural framework that incorporates five contiguous stereocenters. A total synthesis of (±)-actinophyllic acid has been completed that proceeds in only 10 steps from readily available, known compounds and with the isolation of nine intermediates. The synthesis features a novel cascade of reactions of N-stabilized carbocations with π-nucleophiles to create the tetracyclic core of actinophyllic acid in a single chemical operation. This pivotal cascade sequence generates substructures of the actinophyllic acid core that are not otherwise accessible, and one key intermediate was modified to furnish several novel compounds having potentially promising anticancer activity, one of which induces cell death in a wide range of cancer cell lines.
阿廷菲林酸是一种具有独特结构骨架的生物活性吲哚生物碱，其中包含五个连续的手性中心。（±）-阿廷菲林酸的全合成已经完成，仅从易得的已知化合物经过 10 步反应即可实现，同时分离出 9 个中间体。该合成方法的特点是新型 N-稳定碳正离子与π-亲核试剂的级联反应，可在单一化学反应中构建阿廷菲林酸的四环核心。这一关键级联序列生成了阿廷菲林酸核心的亚结构，这些亚结构在其他情况下无法获得，其中一个关键中间体被修饰，得到了几种具有潜在抗肿瘤活性的新型化合物，其中一种在多种癌细胞系中诱导细胞死亡。
