Ibogan, Aspidosperman, Vincamine, and Bisindole Alkaloids from a Malayan Tabernaemontana corymbosa: Iboga Alkaloids with C-20α Substitution

J Nat Prod. 2016 May 27;79(5):1388-99. doi: 10.1021/acs.jnatprod.6b00129. Epub 2016 Apr 14.

Abstract

Ten new indole alkaloids (1-10) comprising five ibogan, two aspidosperman, one vincamine, and two bisindole alkaloids, in addition to 32 known alkaloids, were isolated from the stem-bark extract of a Malayan Tabernaemontana corymbosa. The structures of these alkaloids were determined based on analysis of the NMR and MS data and, in five instances (1, 3, 5, 6, 8), confirmed by X-ray diffraction analysis. Two of the iboga alkaloids, conodusines B (2) and C (3), and the iboga-containing bisindole tabernamidine B (10) are notable for the presence of an α-substituted acetyl group at C-20 of the iboga carbon skeleton. The iboga alkaloid (+)-conodusine E (5) had MS and NMR data that were identical to those of (-)-ervatamine I, recently isolated from Ervatamia hainanensis. Establishment of the absolute configuration of (+)-conodusine E (5) was based on analysis of the ECD data, correlation with (-)-heyneanine, and X-ray analysis, which showed that (+)-5 belongs to the same enantiomeric series as exemplified by (-)-coronaridine. The configuration at C-20' of the previously reported Tabernaemontana bisindole alkaloid 19'-oxotabernamine (renamed tabernamidine B) required revision based on the present results. Several of the bisindoles showed pronounced in vitro growth inhibitory activity against drug-sensitive and vincristine-resistant KB cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Phytogenic / chemistry
  • Crystallography, X-Ray
  • Drug Screening Assays, Antitumor
  • Humans
  • Ibogaine / analogs & derivatives
  • Indole Alkaloids / chemistry*
  • Indole Alkaloids / isolation & purification*
  • KB Cells
  • Molecular Conformation
  • Molecular Structure
  • Plant Bark / chemistry
  • Plant Leaves / chemistry
  • Stereoisomerism
  • Structure-Activity Relationship
  • Tabernaemontana / chemistry
  • Vincamine / chemistry
  • Vincamine / isolation & purification
  • Vincamine / pharmacology
  • Vincristine / pharmacology

Substances

  • Antineoplastic Agents, Phytogenic
  • Indole Alkaloids
  • Ibogaine
  • coronardine
  • Vincristine
  • Vincamine