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 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.
D002384:Catalysis; D002855:Chromatography, Thin Layer; D003903:Deuterium; D005609:Free Radicals; D006735:Horseradish Peroxidase / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000032:analysis; D008956:Models, Chemical; D010084:Oxidation-Reduction; D010544:Peroxidases / Q000378:metabolism*; D013053:Spectrophotometry; D014747:Vinblastine / Q000031:analogs & derivatives* / Q000378:metabolism
D005609:Free Radicals; C009667:vindoline; C041490:16-O-acetylvindoline; D014747:Vinblastine; D003903:Deuterium; D006861:Hydrogen Peroxide; D006735:Horseradish Peroxidase; D010544:Peroxidases