Epoxide hydrolases as asymmetric catalysts

Epoxide hydrolase enzymes represent a relatively simple and efficient route towards the synthesis of optically enriched epoxides and diols with little or no other functionality, The relative merits and limitations of EHs from the various sources have been discussed. Mammalian liver microsomal epoxide hydrolase (mEH) has been shown to display exceptionally high enantioselectivity towards a wide range of substrates. However, its limited availability has prevented chemists from viewing it as a potential asymmetric catalyst for the production of chiral epoxides and diols, in the same manner, for example, that lipases/esterases have been used in organic synthesis. Large-scale production of the enzyme ought to be possible via expression of the protein in a host bacteria (e.g. E, call), followed by conventional fermentation of the genetically-engineered organism. Epoxide hydrolases from microbial sources, which do not suffer from the drawback of limited availability, have been used to good effect for the production of a range of chiral epoxides and diols. In general, these enzymes do not exhibit such a broad substrate range as mEH, although, as:studies continue, more EH enzymes will be discovered which will extend the range of substrates which may be hydrolysed with acceptable enantioselectivity. The recent paper by Weijers, describing a yeast species (Rhodotorula glutinis) which displayed epoxide hydrolase activity with an exceptional substrate range in addition to superb enantioselectivity in most cases,represents an important achievement in this field. The use of epoxide hydrolase enzymes for the production of enantiopure epoxides will always suffer from the drawback that such reactions are kinetic resolutions, and as such can result in a maximum 50% yield of the required epoxide. If, however, the target of the transformations is the transformed diol, a number of approaches have been adopted in order to optimise yields. The production of enantiopure reagents from meso-compounds or racemates (deracemisation) in high yield is a common goal of synthetic chemists. One area where mEH has exhibited much greater enantioselectivity than its microbial counterparts is in the asymmetric hydrolysis of meso-epoxides to. chiral diols. Generally, meso-epoxides have proved to be relatively poor substrates for microbial EHs. Some of the enzymes described catalyse the hydrolysis of both enantiomers of an epoxide to a single enantiomer of diol (deracemisation). In most cases this activity has been discovered fortuitously, although Faber's group have screened a number of organisms for this type of ability. However, Archer et al. have described the synthesis of an enantiomerically pure diol in high yield and ee from the corresponding racemic epoxide, via sequential enzymic and acid catalysed reactions in a single pot.