Six new bisindole alkaloids of the iboga-vobasine type, vobatensines A-F (1-6), in addition to four known bisindoles (8-11), were isolated from a stem bark extract of a Malayan Tabernaemontana corymbosa. The structures of these alkaloids were determined based on analysis of the spectroscopic data and in the case of vobatensines A (1), B (2), and 16'-decarbomethoxyvoacamine (8) also confirmed by partial syntheses. Nine of these alkaloids (1-5, 8-11) showed pronounced in vitro growth inhibitory activity against human KB, PC-3, LNCaP, HCT 116, HT-29, MCF7, MDA-MB-231, and A549 cancer cells.

Seven new indole alkaloids (1-7) comprising four vobasine, two tacaman, and one corynanthe-tryptamine bisindole alkaloid were isolated from the stem-bark extract of a Malayan Tabernaemontana. Two of the new vobasine alkaloids (1, 3), as well as 16-epivobasine (15) and 16-epivobasenal (17), showed appreciable cytotoxicity toward KB cells (IC50 ca. 5 μg/mL). The structure of the known Tabernaemontana alkaloid tronoharine (8) was revised based on newly acquired NMR data, as well as X-ray diffraction analysis.

Examination of the EtOH extract of the leaves of the Malayan Tabernaemontana corymbosa resulted in the isolation of four new (1−4) and two known bisindole alkaloids (5, 6) of the Aspidosperma−Aspidosperma type. The structures of these alkaloids were determined based on analysis of the spectroscopic data (NMR and HRESIMS). Xray diffraction analyses of the related bisindole alkaloids conophylline (5) and conophyllinine (6) established the absolute configurations. Treatment of the bisindole alkaloid conophylline (5) with benzeneselenic anhydride gave, in addition to the known bisindole polyervinine (7) previously isolated from another Malayan Tabernaemontana, another bisindole product, 8, an isolable tautomer of 7. X-ray diffraction analyses yielded the absolute configurations of both bisindoles and in addition showed that polyervinine (7) exists primarily as the neutral dione structure. The bisindoles (1−8) and the related conophylline-type bisindoles (9−13) 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, A549, HT-29, and HCT 116 cells, with IC 50 values for the active compounds in the 0.01−5 μM range.T he genus Tabernaemontana (Apocynaceae) comprises a large number of species (more than 100) that are distributed over the tropical and subtropical regions of the world, including Africa, Asia, parts of the Americas, the Pacific Islands, and Australia. 1 About 13 species are known to occur in Malaysia (Peninsular Malaysia and Malaysian Borneo), with T. corymbosa being the most varied, as well as the most widely distributed. 1,2 Plants of this genus have been shown to be rich sources of biologically active alkaloids, especially indole alkaloids. 3−9 In continuation of the investigation of the Malayan Tabernaemontana, 10,11 we report herein the isolation, structure, and biological activity of new Aspidosperma− Aspidosperma bisindole alkaloids from T. corymbosa (sample occurring near Taiping, Perak). ■ RESULTS AND DISCUSSIONCompound 1 (conolodinine A) was isolated as a light yellowish oil, with [α] 25 D −180 (c 0.25, CHCl 3 ). The UV spectrum showed absorption maxima at 209, 220, 249, and 324 nm, while the IR spectrum showed bands due to OH/NH at 3376 cm −1 and carbonyl functions at 1716, 1674, and 1609 cm −1 . The HRESIMS data ([M + H] + m/z 793.3448) established the molecular formula as C 44 H 48 N 4 O 10 . The 1 H NMR data (Table 1

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