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

Abstract

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 (IC 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.

Biosynthetically Inspired Transformation of Iboga to Monomeric Post-iboga Alkaloids

“…21 However, the chippiine-and dippinine-type post-iboga alkaloids 22 have never succumbed to synthesis despite their structure exposure to the synthetic community for over 30 years. 23 Furthermore, a recent outburst of isolation reports of post-iboga alkaloids 11,12,14,17,[24][25][26][27][28][29] rekindled interest in this family of natural products and has been challenging the synthetic community.…”

Direct Conversion of 3-(2-Nitroethyl)-1H-Indoles into 2-(1H-Indol-2-yl)Acetonitriles

“…However, both allowed for only trace amounts of 6ba (entries 6,7). In contrast, thionyl chloride gave moderate to fair yields with most amine additives tested (entries [8][9][10][11]. Encouraged by these results, we further explored an in situ phosphorylation of nitronate species with POCl 3 .…”

“…Derivatives of 1H-indole-2-acetic acid are common, naturally occurring indoline alkaloids with important bioactivities [1][2][3][4][5][6][7][8][9][10]. These compounds were used as key intermediates in total syntheses of several natural products and nonnatural pharmaceutical agents [11][12][13][14][15][16][17].…”

Anticancer activity of bisindole alkaloids derived from natural sources and synthetic bisindole hybrids

“…[58] Vobasinyl-iboga-type bisindole alkaloids taburnaemines A and C-I, isolated from the twigs and leaves of T. corymbosa, exhibited potential in vitro antiproliferative activity against A549, MDA-MB-231, MCF-7, KB, and P-glycoprotein-overexpressing multidrugresistant KB cancer cell lines with IC 50 values of 2.6-9.8 μM (SRB assay). [59] Among them, the representative taburnaemine I (26; IC 50 :…”