Epoxide hydrolases enantiopure epoxides/diols

Enantiopure cis- and trans-linalool oxides are found in several plants and fruits and constitute the main aroma components of oolong and black tea. These compounds were prepared from 2,3-epoxylinalyl acetate (Fig. 11.2-17) 119. The key step consists of a separation of the diastereomeric mixture of the starting epoxide by employing an epoxide hydrolase preparation derived from Rhodococcus sp. NCIMB 11216, which furnished the product diol and remaining epoxide in excellent diastereomeric excess (de >98%). Further follow-up chemistry gave both linalool oxide isomers on a preparative scale in excellent diastereomeric and enantiomeric purities. 

Over the past few years, an impressive array of epoxide hydrolases has been identified from microbial sources. Due to the fact that they can be easily employed as whole-cell preparations or crude cell-free extracts in sufficient amounts by fermentation, they are just being recognized as highly versatile biocatalysts for the preparation of enantiopure epoxides and vicinal diols. The future will certainly bring an increasing number of useful applications of these systems to the asymmetric synthesis of chiral bioactive compounds. As for all enzymes, the enantioselectivity of... 

For the enantioselective preparations of chiral synthons, the most interesting oxidations are the hydroxylations of unactivated saturated carbons or carbon-carbon double bonds in alkene and arene systems, together with the oxidative transformations of various chemical functions. Of special interest is the enzymatic generation of enantiopure epoxides. This can be achieved by epoxidation of double bonds with cytochrome P450 mono-oxygenases, w-hydroxylases, or biotransformation with whole micro-organisms. Alternative approaches include the microbial reduction of a-haloketones, or the use of haloperoxi-dases and halohydrine epoxidases [128]. The enantioselective hydrolysis of several types of epoxides can be achieved with epoxide hydrolases (a relatively new class of enzymes). These enzymes give access to enantiopure epoxides and chiral diols by enantioselective hydrolysis of racemic epoxides or by stereoselective hydrolysis of meso-epoxides [128,129]. 

Fig. 14.4.1.2. Schematic diagram of a two-phase hollow-fiber membrane bioreactor system for hydrolytic epoxide resolution. [After reference 8]. The yeast cells contain an epoxide hydrolase that enantioselectively hydrolyzes racemic epoxide resulting in enantiopure epoxide that partitions to the organic phase. Diol produced partitions to the water phase.

Epoxide hydrolase has emerged as an important enzyme for the asymmetric synthesis of enantiopure epoxides and diols [24]. The hydrolase HXN-200 has been shown to catalyse the enantioselective hydrolysis of meso epoxides to give optically active diols (Scheme 4.14) [25]. A related group of enzymes is the haloalkane dehalogenases that display epoxide hydrolase activity with nucleophiles other than water (Scheme 4.15) [26]. 

Pedragosa-Moreau, S., Archelas, A. and Furstoss, R. (1996) Microbiological transformations. 31. Synthesis of enantiopure epoxides and vicinal diols using fungal epoxide hydrolase mediated hydrolysis. Tetrahedron Lett, 37,3319-3322. 

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