Tyrosinase-catalysed oxidation of the new melanocytotoxic agent N-4-hydroxyphenylglycine: Unusual cleavage of the 4-aminophenol ring to muconic semialdehyde derivatives

Article abstract of DOI:10.1016/S0040-4020(01)80498-1

Oxidation of N-4-hydroxyphenylglycine (1) with tyrosinase in phosphate buffer at pH 6.8 results in two major products, which have been isolated and identified as the novel carboxymethylaminomuconic semialdehyde 3 and the related Schiff base 2. Tyrosinase-catalysed oxidation of 4-aminophenol under similar conditions affords the analogous ring-opened products 6 and 7. Formation of these compounds can be envisaged as proceeding through an unusual cleavage of the 4-aminophenol ring subsequent to its enzymatic conversion to the corresponding o-quinone. Besides disclosing new aspects of the oxidative reactivity of the 4-aminophenol system, the results of this study provide a chemical background to look into the mechanism of the cytotoxic effects of 1 towards human melanoma cells.