Institute of Organic Chemistry, University of Würzburg, Am Hubland, D-97074 Würzburg, Germany.
Org Biomol Chem. 2018 Feb 28;16(9):1581-1590. doi: 10.1039/c7ob03092d.
Two unique pentacyclic N,C-coupled naphthylisoquinolines, the ancistrocyclinones A (5) and B (6), were discovered in the Chinese liana Ancistrocladus tectorius. Furthermore, six known, likewise N,C-coupled alkaloids, viz., ancistrocladinium A (7a) and its mono- and bisphenolic analogs 8a and 9a were isolated, along with their atropo-diastereomers 7b, 8b, and 9b. The stereostructures of 5 and 6 were determined by HRESIMS, 1D and 2D NMR, oxidative degradation, and ECD calculations. The pentacyclic ancistrocyclinones A (5) and B (6) are structurally similar to berberine alkaloids - yet arising from a most different biosynthetic pathway: they are apparently formed by N,C-coupling of their polyketide-derived molecular halves, followed by oxidative cyclo-condensation. Biomimetic conversion of the co-occurring 4'-O-demethylancistrocladinium A (8a) to ancistrocyclinone A (5) via a quinoid intermediate supported the postulated pathway. Ancistrocyclinone A (5) was found to significantly inhibit the viability of drug-sensitive human leukemia (CCRF-CEM) and multidrug-resistant tumor cells (CEM/ADR5000) with comparable efficacies.
两种独特的五环 N,C-偶联萘基异喹啉，即Ancistrocyclinones A（5）和 B（6），在中国藤本植物Ancistrocladus tectorius 中被发现。此外，还分离出了另外六种同样为 N,C-偶联生物碱，即 Ancistrocladinium A（7a）及其单酚和双酚类似物 8a 和 9a，以及它们的对映体 7b、8b 和 9b。通过高分辨质谱（HRESIMS）、1D 和 2D NMR、氧化降解和 ECD 计算确定了 5 和 6 的立体结构。五环 Ancistrocyclinones A（5）和 B（6）在结构上与小檗碱类生物碱相似——但它们来自于非常不同的生物合成途径：它们显然是由其聚酮衍生的分子半部分的 N,C-偶联形成的，然后进行氧化环缩合。同时存在的 4'-O-去甲Ancistrocladinium A（8a）通过醌型中间体仿生转化为 Ancistrocyclinone A（5），支持了所提出的途径。Ancistrocyclinone A（5）被发现对药物敏感的人白血病（CCRF-CEM）和多药耐药肿瘤细胞（CEM/ADR5000）的活力具有显著的抑制作用，且具有相当的疗效。
