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 <i>Tabernaemontana corymbosa</i> resulted in the isolation of three new alkaloids, viz., cononuridine (<b>1</b>), an unusual hexacyclic, iboga-derived, monoterpenoid indole characterized by contraction of the tetrahydroazepine C-ring and incorporation of an additional isoxazolidine ring, taberisidine (<b>2</b>), a <i>seco</i>-corynanthean alkaloid, and conofolidine (<b>3</b>), an <i>Aspidosperma</i>-<i>Aspidosperma</i> 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 <b>1</b> and <b>3</b> and the absolute configuration of the novel pyridopyrimidine indole alkaloid vernavosine (<b>4</b>) were confirmed by X-ray diffraction analysis. A reasonable biosynthesis route to cononuridine starting from an iboga precursor is presented