ChemInform Abstract: Aromatic Hydroxylations by Flavins: Evidence on Direct Attack of Phenylalanine by Flavin Radical Species.

Abstract

Abstract In 0.05–12.0 N acidic solutions, the 5-ethyl-3-methyllumiflavosemiquinone 5 (and/or 5H + ) spontaneously arose from the corresponding flavinium cation 4 . Raising the temperature from 20 to 50°C, considerably increased the reaction rates with no significant changes in the yields of 5 ( 5H + ). The spontaneous one-electron reduction of 4 requires a coupling with a one-electron oxidation of another flavin such as 5-ethyl-4 a -hydroxy-3-methyl-4 a ,5-dihydroflavin pseudobase 1 . The latter, being in equilibrium with 4 , can be oxidized to give the transient 5-ethyl-4 a -hydroxy-3-methyllumiflavin radical 2 . This is the protonated form of a flavinoxy radical 3 a,b , a product of a homolysis of the OO bond in a dihydroflavin hydroperoxide. As an alternative to the homolysis mentioned, the one-electron oxidation of 1 provides the principle to develop a new hydroxylating model system that does not require a dihydroflavin hydroperoxide as a starting compound. Using phenylalanine as a test substrate, the anaerobic formation of tyrosine and its o - and m -hydroxyphenylalanine isomers was established. This achievement is a strong experimental support for the hypothesis that flavin radical species like 2 may directly attack an aromatic. Evidence was obtained on some accumulation of an intermediate that is not a hydroxycyclohexadienyl radical. It was shown to react in a secondary, oxidative chain reaction, remarkably increasing the yields of aromatic hydroxylation without any further supply of flavin.