Artificial Enzymes for Diels‐Alder Reactions

The Diels‐Alder (DA) reaction is a cycloaddition of a conjugated diene and an alkene (dienophile) leading to the formation of a cyclohexene derivative through a concerted mechanism. As DA reactions generally proceed with a high degree of regio‐ and stereoselectivity, they are widely used in synthetic organic chemistry. Considering eco‐conscious public and governmental movements, efforts are now directed towards the development of synthetic processes that meet environmental concerns. Artificial enzymes, which can be developed to catalyze abiotic reactions, appear to be important synthetic tools in the synthetic biology field. This review describes the different strategies used to develop protein‐based artificial enzymes for DA reactions, including for in cellulo approaches. It is crucial for chemists nowadays to develop processes that respect the environment, and synthetic biology is an emerging field to meet such concerns. Diels‐Alder cycloaddition is a key reaction in synthesis, and efforts have been devoted to developing artificial enzymes to catalyze this reaction. This review summarizes the strategies employed to produce protein‐based artificial Diels‐Alderases.