Taburnaemines A-I, Cytotoxic Vobasinyl-Iboga-Type Bisindole Alkaloids from Tabernaemontana corymbosa

Nineteen vobasinyl-ibogan-type bisindole Alkaloids, including nine new compounds, taburnaemines A-I (1-9), were isolated from the twigs and leaves of Tabernaemontana corymbosa. The structures and absolute configurations of the new Alkaloids were determined by a combination of MS, NMR, and ECD analyses. Alkaloids 1-5 contain a rare 1,3-oxazinane moiety in the vobasinyl unit, while 6 has an uncommon 1,3-oxazolidine moiety in the iboga unit. The absolute configurations of alkaloid 1 and the known alkaloid tabernaecorymbosine A (10) were confirmed by single-crystal X-ray diffraction analysis. All of the bisindole Alkaloids, except 2 and 16'-decarbomethoxytabernaecorymbosine A (14), showed antiproliferative activity (IC₅₀ 2.6-9.8 μM) against several human Cancer cell lines, including A-549, MDA-MB-231, MCF-7, KB, and P-glycoprotein-overexpressing multidrug-resistant KB cells. The preliminary structure-activity relationship correlations are also discussed.