Roger Adams Laboratory, Department of Chemistry, University of Illinois, Urbana, Illinois 61801, United States.
Cancer Center at Illinois, University of Illinois, Urbana, Illinois 61801, United States.
J Am Chem Soc. 2021 Feb 3;143(4):2138-2155. doi: 10.1021/jacs.0c12569. Epub 2021 Jan 19.
The isomalabaricanes comprise a large family of marine triterpenoids with fascinating structures that have been shown to be selective and potent apoptosis inducers in certain cancer cell lines. In this article, we describe the successful total syntheses of the isomalabaricanes stelletin A, stelletin E, and rhabdastrellic acid A, as well as the development of a general strategy to access other natural products within this unique family. High-throughput experimentation and computational chemistry methods were used in this endeavor. A preliminary structure-activity relationship study of stelletin A revealed the core motif of the isomalabaricanes to be critical for their cytotoxic activity.
异马巴烷类化合物是一大类具有迷人结构的海洋三萜类化合物，已被证明在某些癌细胞系中具有选择性和强效的凋亡诱导作用。在本文中，我们描述了异马巴烷类化合物stelletin A、stelletin E 和 rhabdastrellic acid A 的全合成的成功，以及开发一种通用策略来获得该独特家族中其他天然产物的方法。在这项努力中使用了高通量实验和计算化学方法。对 stelletin A 的初步结构-活性关系研究表明，异马巴烷类化合物的核心结构对于其细胞毒性活性至关重要。
