Epoxides biotransformation

For a review on epoxide hydrolases and related enzymes in the context of organic synthesis, see Faber, K. Biotransformations in Organic Chemistry, Springer New York 2004. 

The metabolism of foreign compounds (xenobiotics) often takes place in two consecutive reactions, classically referred to as phases one and two. Phase I is a functionalization of the lipophilic compound that can be used to attach a conjugate in Phase II. The conjugated product is usually sufficiently water-soluble to be excretable into the urine. The most important biotransformations of Phase I are aromatic and aliphatic hydroxylations catalyzed by cytochromes P450. Other Phase I enzymes are for example epoxide hydrolases or carboxylesterases. Typical Phase II enzymes are UDP-glucuronosyltrans-ferases, sulfotransferases, N-acetyltransferases and methyltransferases e.g. thiopurin S-methyltransferase. 

The numerous biotransformations catalyzed by cytochrome P450 enzymes include aromatic and aliphatic hydroxylations, epoxidations of olefinic and aromatic structures, oxidations and oxidative dealkylations of heteroatoms and as well as some reductive reactions. Cytochromes P450 of higher animals may be classified into two broad categories depending on whether their substrates are primarily endogenous or xenobiotic substances. Thus, CYP enzymes of families 1-3 catalyze... 

Residues of PCBs in animal tissues include not only the original congeners themselves, but also hydroxy metabolites that bind to cellular proteins, for example, transthyretin (TTR Klasson-Wehler et al. 1992 Brouwer et al. 1990 Fans et al. 1993). Small residues are also found of methyl-sulfonyl metabolites of certain PCBs (Bakke et al. 1982, 1983). These appear to originate from the formation of glutathione conjugates of primary epoxide metabolites, thus providing further evidence of the existence of epoxide intermediates. Further biotransformation, including methylation, yields methyl-sulfonyl products that are relatively nonpolar and persistent. 

Whereas the metabolism of aromatic hydrocarbons takes place by dioxygenation, their biotransformation by yeasts and fungi is normally initiated by monooxygenation to the epoxide followed by hydrolysis to the trani-dihydrodiols. Phenols may subsequently be formed either by elimination or by nonenzymatic rearrangement of the epoxide ... 

Virtually all organisms possess biotransformation or detoxification enzymes that convert lipophilic xenobiotics to water-soluble and excretable metabolites (Yu et al. 1995). In the metabolic process, PAHs are altered by Phase I metabolism into various products such as epoxides, phenols,... 

G. Bellucci, C. Chiappe, A. Cordoni, F. Marioni, The Rabbit Liver Microsomal Biotransformation of 1,1-Dialkylethylenes Enantioface Selection of Epoxidation and Enantioselectivity of Epoxide Hydrolysis , Chirality 1994, 6, 207 - 212. 

In connection with our own work on the enzyme-catalysed hydrolysis of cyclohexene epoxide with various fungi we made the unexpected observation that the microorganism Corynesporia casssiicola DSM 62475 was able to interconvert the (1R,2R) and (1S,2S) enantiomers of the product, trans cyclohexan-1,2-dioI 25. As the reaction proceeded the (1R,2R) enantiomer was converted to the (1S,2S) enantiomer [20]. If the racemic trans diol 25 was incubated with the growing fungus over 5 days, optically pure (> 99 % e. e.) (1 S,2S) diol 25 could be isolated in 85% yield. Similarly biotransformation of cis (meso) cycIohexan-1,2-diol 26 yielded the (1S,2S) diol 25 in 41 % (unoptimized) yield (Scheme 11). 

Perez, H.L. and Osterman-Golkar, S. Biotransformation of the double bond in allyl glycidyl ether to epoxide ring. Evidence from hemoglobin adducts in mice, Chem. Biol. Interact., 125(l) 17-28, 2000. 

Hissink E, Van Ommen B, Bogaards JJ, et al. 1996. Hepatic epoxide concentrations during biotransformation of 1,2 and 1,4,-dichlorobenzene. Biological Reactive Intermediates V. New York Plenum Press. 

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