Naphthylisoindolinone alkaloids: the first ring-contracted naphthylisoquinolines, from the tropical liana Ancistrocladus abbreviatus, with cytotoxic activity.

Abstract

The West African liana Ancistrocladus abbreviatus is a rich source of structurally most diverse naphthylisoquinoline alkaloids. From its roots, a series of four novel representatives, named ancistrobrevolines A-D (14-17) have now been isolated, displaying an unprecedented heterocyclic ring system, where the usual isoquinoline entity is replaced by a ring-contracted isoindolinone part. Their constitutions were elucidated by 1D and 2D NMR and HR-ESI-MS. The absolute configurations at the chiral axis and at the stereogenic center were assigned by using experimental and computational electronic circular dichroism (ECD) investigations and a ruthenium-mediated oxidative degradation, respectively. For the biosynthetic origin of the isoindolinones from 'normal' naphthyltetrahydroisoquinolines, a hypothetic pathway is presented. It involves oxidative decarboxylation steps leading to a ring contraction by a benzilic acid rearrangement. Ancistrobrevolines A (14) and B (15) were found to display moderate cytotoxic effects (up to 72%) against MCF-7 breast and A549 lung cancer cells and to reduce the formation of spheroids (mammospheres) in the breast cancer cell line.