Epoxide hydrolases vicinal diol

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... 

The epoxide hydrolases (EHs ECS.3.2.3) hydrate simple epoxides to vicinal diols, and they hydrate arene oxides to trans-dihydrodiols (also see Table 8.1). 

S. Wu, A. Li, Y.S. Chin, Z. Li, Enantioselective hydrolysis of racemic and mesu-epoxides with recombinant Escherichia coli expressing epoxide hydrolase from Sphingomonas sp. FlXN-200 preparation of epoxides and vicinal diols in high ee and high concentration, ACS Catal. 3... 

Epoxide hydrolases (EH) are promising biocatalysts for the preparation of chiral epoxides and vicinal diols and can be effectively used in the resolution of racemic epoxides. There are number of reviews published on the synthetic application of epoxide hydrolase and preparation of chiral epoxides [52-57] and additional information can be found elsewhere in this book. 

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. 

Botes, A.L., Letter, J., Labuschagne, M. and Mitra, R.K. (2005) Methods for the preparation of optically active epoxides and vicinal diols from styrene epoxides using enantiose-lective epoxide hydrolases derived from yeasts. WO Patent 100569 A2 (CSIR, October 27, 2005). 

Chiral epoxides and their corresponding vicinal diols are very important intermediates in asymmetric synthesis [163]. Chiral nonracemic epoxides can be obtained through asymmetric epoxidation using either chemical catalysts [164] or enzymes [165-167]. Biocatalytic epoxidations require sophisticated techniques and have thus far found limited application. An alternative approach is the asymmetric hydrolysis of racemic or meso-epoxides using transition-metal catalysts [168] or biocatalysts [169-174]. Epoxide hydrolases (EHs) (EC 3.3.2.3) catalyze the conversion of epoxides to their corresponding vicinal diols. EHs are cofactor-independent enzymes that are almost ubiquitous in nature. They are usually employed as whole cells or crude... 

The activities of both haloalkanol dehalogenase (halohydrin hydrogen lyase) that catalyzes the formation of epoxides from alkanes with vicinal hydroxyl and halogen groups, and epoxide hydrolase that brings about hydrolysis of epoxyalkanes to diols are involved in a number of degradations that involve their sequential operation. 

Cholesterol epoxide hydrolase, which is expressed in the endoplasmic reticulum and catalyzes the trans-addition of H20 to cholesterol 5,6a-ox-ide and cholesterol 5,6/3-oxide, as well as to a number of other steroid 5,6-oxides. The products are the corresponding vicinal diols [54][55],... 

The cytosolic enzyme leukotriene A4 hydrolase (EC 3.3.2.6), which ster-eoselectively converts leukotriene A4 (LTA4) to leukotriene B4 [56], This enzyme catalyzes the hydrolytic cleavage of the 5,6-epoxide ring in LTA4, but, in contrast to what happens with other EHs, the product is not a vicinal diol but a 5,12-diol. As a zinc metalloenzyme, LTA4 hydrolase does not appear to be related to any other epoxide hydrolase. 

Keywords Epoxide, Vicinal diol. Epoxide hydrolase. Biocatalysis, Enantio-convergent. 

Fig. 10. Summary of the enzymatic metabolism of arachidonic acid by cytochrome AaSO. The epoxides presumably all have the as configuration although this has only been shown for the w6 oxide. The epoxides are hydrolysed by epoxide hydrolase into the vicinal diols. Arachidonic acid and the vicinal diols may be further metabolised by wl- and w2-hydroxylation.

The mechanism of epoxide hydrolase-catalyzed hydrolysis has been elucidated from microsomal epoxide hydrolase (MEH) and bacterial enzymes to involve the trans-antiperiplanar addition of water to epoxides and arene oxides to give vicinal diol products. In general, the reaction occurs with inversion of configuration at the oxirane carbon atom to which the addition takes place and involves neither cofactors nor metal ions [565]. Two types of mechanism are known (Scheme 2.87). 

Fig. 13.5 Linoleic acid (Z.,4), eicosapentaenoic acid ( pDP ). Epoxide hydrolases ( Hs) hydrolyze these ep-( R4), and docosahexaenoic acid ( DHA) are all me- oxides to the corresponding vicinal diols, dihydroxyocta-tabolized by CYP epoxygenases to form epoxyocta- decamonoenoic acids (DiHOMEs), dihydroxyeicosatet-decamonoenoic acids (EpOMEs), epoxyeicosatetrae- raenoic acids (DiHETEs), and dihydroxydocosapentae-noic acids (EpETEs), and epoxydocosapentaenoic acids noic acids (DtffD/M), respectively...

Chang, D., Wang, Z., Heringa, M.R, Wirthner, R., Witholt, B. and Li, Z. (2003) Highly enantioselective hydrolysis of alicyclic meso-epoxides with a bacterial epoxide hydrolase from Sphingomonas sp. HXN-200 simple synthesis of alicyclic vicinal frans-diols. Chem. Commun., 960-961. 

Ordinary alkenes are also subject to attack by MFOs to form epoxides. These epoxides, since they are not arene oxides, most commonly undergo hydrolysis catalyzed by epoxide hydrolase to give vicinal diols (Figure 7.10). 

Figure 7.10 Ordinary alkenes also undergo epoxidation mediated by MFO.These have little incentive to rearrange and so they generally serve as substrates for epoxide hydrolase to form vicinal diols. In this example the allylic group of the hypnotic agent secobarbital is epoxidized, but the epoxide is not observed among the isolated metabolites. Instead it is the diol that is found as a major metabolite.

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