Leurosine biotransformations: an unusual ring-fission reaction catalyzed by peroxidase

Chem Res Toxicol. 1988 Jul-Aug;1(4):238-42. doi: 10.1021/tx00004a009.

Abstract

The dimeric Vinca alkaloid leurosine undergoes an unusual fission of the piperidine ring of the Iboga substructure when reacted with horseradish peroxidase and hydrogen peroxide. A preparative-scale oxidation of leurosine provided 15'-hydroxycatharinine, which was identified by infrared and proton and carbon-13 NMR spectroscopies and high-resolution mass spectrometry. A proposed pathway for the formation of 15'-hydroxycatharinine involves radical and iminium intermediates and cleavages of a putative diol. The enzymatic transformation product is 3 orders of magnitude less active than leurosine or vinblastine in vitro, in inhibiting the polymerization of tubulin.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / metabolism
  • Biotransformation
  • Brain / metabolism
  • Cattle
  • Horseradish Peroxidase / metabolism*
  • Molecular Structure
  • Tubulin / drug effects
  • Tubulin / metabolism
  • Vinca Alkaloids / metabolism*
  • Vinca Alkaloids / pharmacology

Substances

  • Antineoplastic Agents, Phytogenic
  • Tubulin
  • Vinca Alkaloids
  • leurosine
  • Horseradish Peroxidase