Model reactions for the quinone-containing copper amine oxidases. Anaerobic reaction pathways and catalytic aerobic deamination of activated amines in buffered aqueous acetonitrile

Article abstract of DOI:10.1021/ja00116a014

The quinone form 2 of the N-pivaloyl derivative of 6-hydroxydopamine, developed as a model for the quinone form of the peptidyl 2,4,5-trihydroxyphenylalanine (TOPA) cofactor of the copper amine oxidases, is an effective catalyst for aerobic oxidative deamination of activated amines (e.g., benzylamine and cinnamylamine) in buffered aqueous acetonitrile. The reaction efficiency increases at higher pH and exceeds six turnovers for benzylamine at pH 10, where an apparent α-C deuterium kinetic isotope effect of 10 is observed. The yield is limited by the eventual conversion of 2 to the corresponding benzoxazoles (confirming nucleophilic attack of amine at the most electrophilic C-5 carbonyl) and other forms which are incapable of oxidative recycling. Copper(II) inhibits the reaction, in contrast to the free TOPA amino acid, which deaminates benzylamine only when Cu(II) is present. Under anaerobic "single turnover" conditions, the products of catalyst reduction are (alkylamino)resorcinols formed via redox cycling reactions of the initial reduced cofactor (either benzenetriol or aminoresorcinol) in the presence of excess amine. Unactivated amines exhibit low deaminative turnover and at high concentrations effect side-chain cleavage of the quinone catalyst induced by C-1 Michael addition of amine to the intermediate N-alkyl quinone imines.