Epoxide Hydrolases and their Application in Organic Synthesis

Abstract

The scope of this chapter is to provide a comprehensive overview of the most interesting applications of epoxide hydrolases (EHs) for the formation of enantiopure epoxides and/or diols, which are valuable chiral building blocks and key intermediates for the synthesis of various natural products or pharmacologically active compounds. Indeed, EHs have proved to be outstanding biocatalysts due to the fact that they are robust enzymes, which do not need any cofactors for catalysis, they usually exhibit a relatively large substrate spectrum, and they often possess excellent stereo-, regio-, and chemoselectivities. In addition, the development of molecular biology tools such as site-directed mutagenesis and laboratory evolution (error-prone PCR, DNA shuffling, and iterative saturation mutagenesis) further offers the possibility to modify existing EHs, leading to the improvement of one or more enzyme characteristics such as specific activity, substrate specificity, or enantioselectivity to cite a few. Finally, besides the classical kinetic resolution of a racemate with its intrinsic limitation of a 50% maximum theoretical yield in both enantiomerically pure residual epoxide and formed diol, EHs can also be used in the stereoselective desymmetrization of meso-epoxides or in the enantioconvergent hydrolysis of racemic epoxides, both processes theoretically providing enantiopure diol products in 100% yield.