A Hexacyclic, Iboga-Derived Monoterpenoid Indole with a Contracted Tetrahydroazepine C‑Ring and Incorporation of an Isoxazolidine Moiety, a <i>Seco</i>-Corynanthean, an <i>Aspidosperma-Aspidosperma</i> Bisindole with Anticancer Properties, and the Absolute Configuration of the Pyridopyrimidine Indole Alkaloid, Vernavosine

Examination of the EtOH extract of the Malayan Tabernaemontana corymbosa resulted in the isolation of three new alkaloids, viz., cononuridine (1), an unusual hexacyclic, iboga-derived, monoterpenoid indole characterized by contraction of the tetrahydroazepine C-ring and incorporation of an additional isoxazolidine ring, taberisidine (2), a seco-corynanthean alkaloid, and conofolidine (3), an Aspidosperma-Aspidosperma bisindole that showed pronounced in vitro growth inhibitory activity against an array of human cancer cell lines, including KB, vincristine-resistant KB, PC-3, LNCaP, MCF7, MDA-MB-231, HT-29, and HCT 116 cells. The structures and absolute configurations of 1 and 3 and the absolute configuration of the novel pyridopyrimidine indole alkaloid vernavosine (4) were confirmed by X-ray diffraction analysis. A reasonable biosynthesis route to cononuridine starting from an iboga precursor is presented.对马来亚狗牙花（Tabernaemontana corymbosa）的乙醇提取物进行研究，成功分离得到三种新生物碱：科诺乌里定（1）——一种罕见的六环依波加（iboga）衍生单萜吲哚类化合物，其结构特征为四氢氮䓬C环发生收缩并引入额外的异恶唑烷环；塔贝里西定（2），属于开环柯楠型（seco-corynanthean）生物碱；以及科诺福立定（3）——一种双阿枯米辛（Aspidosperma）型双吲哚生物碱，该化合物对一系列人类癌细胞系展现出显著的体外生长抑制活性，包括KB细胞、长春新碱耐药KB细胞、PC-3细胞、LNCaP细胞、MCF7细胞、MDA-MB-231细胞、HT-29细胞及HCT 116细胞。化合物1与3的结构及绝对构型，还有新型吡咯并嘧啶吲哚生物碱弗纳沃辛（4）的绝对构型，均通过X射线衍射分析（X-ray diffraction analysis）得以确证。本文还报道了以依波加类前体为起始原料合成科诺乌里定的合理生物合成途径。