Enzyme‐Catalysed Synthesis of Secondary and Tertiary Amides

The synthesis of the amide bond between an amine and a carboxylic acid is one of the most significant reactions in industrial pharmaceutical synthesis. Despite the apparent simplicity of synthetic methods for amide bond formation, many of these are disadvantaged by their requirement for toxic or hazardous reagents for the activation of the acid component, or poor atom economy resulting from the need for stoichiometric amounts of coupling reagents. In this context, biocatalysis has emerged as an alternative catalytic method for amide bond formation, presenting the advantages of both environmentally benign reagents and conditions and also atom economy. In this review we detail developments in the enzyme‐catalysed preparation of secondary and tertiary amides for the synthesis of pharmaceutical‐type molecules and review the applications of hydrolases, such as lipases and penicillin acylases, to these reactions. We also summarise the activity of ATP‐dependent enzymes for amide bond formation and assess their potential for the preparative synthesis of amides from carboxylic acids and amines in aqueous media.