Laccase-induced cross-coupling of 4-aminobenzoic acid with para-dihydroxylated compounds 2,5-dihydroxy-N-(2-hydroxyethyl)-benzamide and 2,5-dihydroxybenzoic acid methyl ester

A fungal laccase from Trametes villosa (EC 1.10.3.2 p-phenoloxidase) was used to mediate the oxidation and cross-coupling of two para-dihydroxylated benzoic acid derivatives with 4-aminobenzoic acid. The incubation of 2,5-dihydroxy-N-(2-hydroxyethyl)-benzamide and 4-aminobenzoic acid with laccase under oxygen conditions resulted in the formation of 2-(4'-carboxy-anilino)-N-(2-hydroxyethyl)-3,6-dioxo-1,4-cyclohexadien-1-carboxamide as the main product (yield > 85%). When 2,5-dihydroxybenzoic acid methyl ester was a co-substrate of 4-aminobenzoic acid, 2-(4'-carboxy-anilino)-N-(2-hydroxyethyl)-3,6-dioxo-1,4-cyclohexadien-1-carboxy methyl ester was produced (yield > 75%). Both products were N-C coupling dimers consisting of para-quinone and benzoic acid moieties. The formation of quinone structures in the presence of T villosa laccase may be useful in pharmaceutical synthesis. Because of high product yields and low amount of by-products laccase of T villosa seems to be a suitable enzyme among laccases acting at pH 5 for the synthesis of heterologous dimers. (c) 2005 Elsevier B.V. All rights reserved.