One-Pot biocatalytic oxidation/Michael addition: a green strategy for the synthesis of bioactive compounds

Biocatalysis is gaining notable attention in organic synthesis leading to the employment of environmentally benign reaction conditions, thus affording new molecular structures with high selectivity. Among the most recently studied biocatalysts, laccases pose a challenge for fine chemistry purposes. They are multi-copper oxidases involved in the biosynthesis of a large variety of bioactive natural products through the formation of organic radicals as primary products [1]. These enzymes are normally used in laboratory for oxidative coupling reactions, bypassing the use of toxic oxidising agents [1]. More recently, laccases have been employed in single step mild-oxidation/ conjugate addition [2] or in cascade reactions to provide organic compounds of pharmaceutical interest [3]. Here, the development of a green procedure for the synthesis of hybrid compounds containing the phenolic and benzoXazole biaoctive scaffolds is reported. A multi-level factorial mathematical model (Boxen-Benken-Design) was employed for the simultaneous study of multiple factors with a reduced number of experiments. The optimized process suggested by the model was applied for the synthesis of hybrids with different structural features. Regardless of the type of phenolic compound used, quercetin, daidzein, or phenylacetic acid, the products were obtained with high yield (60-85%) highlighting the robustness of the methodology developed.