Leurosine biotransformations: an unusual ring-fission reaction catalyzed by peroxidase.
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.
Goswami
A
A
Division of Medicinal Chemistry and Natural Products, College of Pharmacy, University of Iowa, Iowa City 52242.
Macdonald
T L
TL
Hubbard
C
C
Duffel
M W
MW
Rosazza
J P
JP
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000378:metabolism; D001711:Biotransformation; D001921:Brain / Q000378:metabolism; D002417:Cattle; D006735:Horseradish Peroxidase / Q000378:metabolism*; D015394:Molecular Structure; D014404:Tubulin / Q000187:drug effects / Q000378:metabolism; D014748:Vinca Alkaloids / Q000378:metabolism* / Q000494:pharmacology
D000972:Antineoplastic Agents, Phytogenic; D014404:Tubulin; D014748:Vinca Alkaloids; C002067:leurosine; D006735:Horseradish Peroxidase