Epoxide Hydrolases and Their Synthetic Applications

Chiral epoxides and 1,2-diols, which are central building blocks for the asymmetric synthesis of bioactive compounds, can be obtained by using enzymes--i.e. epoxide hydrolases--which catalyse the enantioselective hydrolysis of epoxides. These biocatalysis have recently been found to be more widely distributed in fungi and bacteria than previously expected. Sufficient sources from bacteria, such as Rhodococcus and Nocardia spp., or fungi, as for instance Aspergillus and Beauveria spp., have now been identified. The reaction proceeds via an SN2-specific opening of the epoxide, leading to the formation of the corresponding trans-configured 1,2-diol. For the resolution of racemic monosubstituted and 2,2- or 2,3-disubstituted substrates, various fungi and bacteria have been shown to possess excellent enantioselectivities. Additionally, different methods, which lead to the formation of the optically pure product diol in a chemical yield far beyond the 50% mark (which is intrinsic to classic kinetic resolutions), are discussed. In addition, the use of non-natural nucleophiles such as azides or amines provides access to enantiomerically enriched vicinal azido- and amino-alcohols. The synthetic potential of these enzymes for asymmetric synthesis is illustrated with recent examples, describing the preparation of some biologically active molecules.