Ancistrosecolines A-F, Unprecedented -Naphthylisoquinoline Alkaloids from the Roots of , with Apoptosis-Inducing Potential against HeLa Cancer Cells.

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.