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

• 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
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm50001a016

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.