Novel dual-enzyme system for synthesis of 2-alkyl and 2-arylbenzoxazoles via aerobic oxidation

Abstract

This study reports a strategy involving biocatalysis to form 2-alkylbenzoxazoles and 2-arylbenzoxazoles specifically via the urease–artificial Vitreoscilla hemoglobin metalloenzyme (ArVHbM)-catalyzed cascade reaction of urea, catechols, and aldehydes. In this system, ArVHbM and urease not only function as catalysts for the crucial initial reactions they also ensure the controllable in situ generation of ammonia to avoid its accumulation and thus prevent its possible toxic effects. The enzymatic method has a wide substrate scope (26 examples) and a green process (water as solvent and air as oxidant) and is superior to known chemical oxidant methods involving the NaIO₄–NH₄OAc system. In addition, we evaluate the value of porphyrin ligand substitution as a strategy to tune and enhance the catalytic properties of hemoproteins in non-natural reactions.