Institute of Organic Chemistry, University of Würzburg, Am Hubland, D-97074 Würzburg, Germany.
Department of Pharmacognosy, Faculty of Pharmacy, Ain-Shams University, Organization of African Unity Street 1, 11566 Cairo, Egypt.
J Nat Prod. 2020 Apr 24;83(4):1139-1151. doi: 10.1021/acs.jnatprod.9b01168. Epub 2020 Mar 3.
Ancistrosecolines A-F (-) are the first -type naphthylisoquinoline alkaloids discovered in Nature. In all these novel compounds, the tetrahydroisoquinoline ring is cleaved, with loss of C-1. They were isolated from the root bark of (Ancistrocladaceae), along with 1--8--demethylancistrobrevine H (), which is the first naturally occurring naphthylisoquinoline lacking the otherwise generally present methyl group at C-1. The stereostructures of the new alkaloids were established by HRESIMS, 1D and 2D NMR, oxidative degradation, and experimental and quantum-chemical ECD investigations. Ancistrosecolines A-F (-) and 1--8--demethylancistrobrevine H () are typical Ancistrocladaceae-type metabolites, i.e., oxygenated at C-6 and -configured at C-3, belonging to the subclasses of 7,1'- and 7,8'-coupled alkaloids. The biaryl linkages of - are rotationally hindered due to bulky -substituents next to the axes. Owing to the constitutionally unsymmetric substitution patterns on each side of the axis, this C-C single bond represents an element of chirality in 1--8--demethylancistrobrevine H () and in ancistrosecolines A-D (-). In ancistrosecolines E () and F (), however, the likewise rotationally hindered biaryl axes do not constitute chiral elements, due to a symmetric substitution pattern, with its identical two methoxy functions at C-6 and C-8 in the phenyl subunit. And these two methoxy groups are, for the first time, not constitutionally heterotopic, but diastereotopic to each other. Ancistrosecoline D () exhibits strong cytotoxicity against HeLa cervical cancer cells. As visualized by Hoechst nuclei staining and by real-time imaging experiments, induced massive nuclei fragmentation in HeLa cells, leading to apoptotic cell death.
阿氏钩藤碱 A-F（-）是自然界中首次发现的第一类萘基异喹啉生物碱。在所有这些新型化合物中，四氢异喹啉环被裂解，失去 C-1。它们是从（钩藤科）的根皮中分离出来的，同时还分离出 1--8--去甲阿氏钩藤碱 H（），这是第一个天然存在的缺乏通常在 C-1 处存在的甲基的萘基异喹啉。新生物碱的立体结构通过高分辨率质谱、1D 和 2D NMR、氧化降解以及实验和量子化学 ECD 研究来确定。阿氏钩藤碱 A-F（-）和 1--8--去甲阿氏钩藤碱 H（）是典型的钩藤科代谢物，即在 C-6 处氧化且 C-3 构型为，属于 7,1'-和 7,8'-偶联生物碱的亚类。由于 - 位的大取代基紧邻轴，因此 - 是旋转受阻的。由于轴两侧的取代模式在结构上不对称，因此 C-C 单键在 1--8--去甲阿氏钩藤碱 H（）和阿氏钩藤碱 A-D（-）中代表手性元素。然而，在阿氏钩藤碱 E（）和 F（）中，由于取代模式对称，其苯亚基上的两个甲氧基功能相同，因此同样旋转受阻的双芳基轴不构成手性元素。而且，这两个甲氧基基团第一次不是在结构上异位，而是具有彼此的立体异位。阿氏钩藤碱 D（）对 HeLa 宫颈癌细胞具有很强的细胞毒性。通过 Hoechst 细胞核染色和实时成像实验观察到，阿氏钩藤碱 D 诱导 HeLa 细胞大量核碎裂，导致细胞凋亡。
