One-Electron Oxidation of Vindoline and 16-O-Acetylvindoline Catalyzed by Peroxidase

The mechanism of oxidation of the alkaloids vindoline (1) and 16-O-acetylvindoline (1a) was examined by use of the reversible redox cycle of horseradish peroxidase (HRP). Oxidation of 1 by HRP resulted in the formation of the enamine dimer 5. The highly reactive radical cation species 2 is an implie...

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Bibliographic Details
Published in:Journal of medicinal chemistry 1985-05, Vol.28 (5), p.629-633
Main Authors: Sariaslani, F. Sima, Duffel, M. W, Rosazza, J. P
Format: Article
Language:English
Subjects:
acetylvindoline
Armoracia lapathifolia
Biological and medical sciences
Catalysis
Chromatography, Thin Layer
Deuterium
Free Radicals
General pharmacology
Horseradish Peroxidase - metabolism
Hydrogen Peroxide - analysis
Medical sciences
Models, Chemical
oxidation
Oxidation-Reduction
peroxidase
Peroxidases - metabolism
Pharmacokinetics. Pharmacogenetics. Drug-receptor interactions
Pharmacology. Drug treatments
Spectrophotometry
Vinblastine - analogs & derivatives
Vinblastine - metabolism
vindoline
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Summary:The mechanism of oxidation of the alkaloids vindoline (1) and 16-O-acetylvindoline (1a) was examined by use of the reversible redox cycle of horseradish peroxidase (HRP). Oxidation of 1 by HRP resulted in the formation of the enamine dimer 5. The highly reactive radical cation species 2 is an implied intermediate in the oxidation process. During the reaction, HRP-I was reduced to HRP-II by abstraction of an electron from vindoline. The vindoline radical thus formed eliminates a second electron and a proton to produce a highly reactive iminium derivative which undergoes intramolecular etherification and dimerization. Oxidation of 16-O-acetylvindoline (1a) by HRP-I results in the production of an iminium derivative 3a concomitant with the formation of HRP-II. The iminium 3a was isolated and characterized and was converted into monodeuterated 1a by reduction with NaBD4. The stoichiometry (HRP-II)/(substrate) was determined to be 4.77 +/- 0.17 for vindoline and 2.27 +/- 0.20 for 16-O-acetylvindoline. The enamine dimer also reduced HRP-I to form HRP-II, but the stoichiometry of this reaction was variable.
ISSN:0022-2623
1520-4804
DOI:10.1021/jm50001a016