Department of Biofunctional Molecular Chemistry, Graduate School of Pharmaceutical Sciences , Chiba University , 1-8-1 Inohana , Chuo-ku , Chiba 260-8675 , Japan.
J Org Chem. 2018 Dec 21;83(24):15312-15322. doi: 10.1021/acs.joc.8b02554. Epub 2018 Dec 4.
The first asymmetric total synthesis of ophiorrhisine A (1), a new cyclic tetrapeptide isolated from Ophiorrhiza nutans, was accomplished via an intramolecular aromatic nucleophilic substitution reaction (IMSAr) of a linear tripeptide to construct a 14-membered paracyclophane ring, resulting in confirmation of its structure and absolute configuration. The structure-activity relationship study of 1 and its derivatives demonstrated that some derivatives possessed cytotoxicity toward human cancer cell lines A549, HT29, and HCT116.
首次完成了来源于 Ophiorrhiza nutans 的新型环状四肽 ophiorrhisine A（1）的不对称全合成，通过线性三肽的分子内芳香亲核取代反应（IMSAr）构建了 14 元的对环芳烃环，从而确定了其结构和绝对构型。1 及其衍生物的构效关系研究表明，一些衍生物对人癌细胞系 A549、HT29 和 HCT116 具有细胞毒性。
