Stereoselective reactions enzyme-catalyzed hydration

Optically inactive starting materials can give optically active products only if they are treated with an optically active reagent or if the reaction is catalyzed by an optically active substance. The best examples are found in biochemical processes. Most biochemical reactions are catalyzed by enzymes. Enzymes are chiral and enantiomerically homogeneous they provide an asymmetric environment in which chemical reaction can take place. Ordinarily, enzyme-catalyzed reactions occur with such a high level of stereoselectivity that one enantiomer of a substance is formed exclusively even when the substrate is achiral. The enzyme ftimarase, for example, catalyzes hydration of the double bond of fumaric acid to malic acid in apples and other fruits. Only the S enantiomer of malic acid is formed in this reaction. 

In contrast to the metabolism of BA and BaP, the 5,6-dihydrodiols formed in the metabolism of DMBA by liver microsomes from untreated, phenobarbital-treated, and 3-methylcholanthrene-treated rats are found to have 5R,6R/5S,6S enantiomer ratios of 11 89, 6 94, and 5 95, respectively (7.49 and Table II). The enantiomeric contents of the dihydrodiols were determined by a CSP-HPLC method (7.43). The 5,6-epoxide formed in the metabolism of DMBA by liver microsomes from 3MC-treated rats was found to contain predominantly (>97%) the 5R,6S-enantiomer which is converted by microsomal epoxide hydrolase-catalyzed hydration predominantly (>95%) at the R-center (C-5 position, see Figure 3) to yield the 5S,6S-dihydrodiol (49). In the metabolism of 12-methyl-BA, the 5S,6S-dihydrodiol was also found to be the major enantiomer formed (50) and this stereoselective reaction is similar to the reactions catalyzed by rat liver microsomes prepared with different enzyme inducers (unpublished results). Labeling studies using molecular oxygen-18 indicate that 5R,68-epoxide is the precursor of the 5S,6S-dihydrodiol formed in the metabolism of 12-methyl-BA (51). 

Enzyme and Nonenzyme Catalysts By nature, enzymes themselves are chiral and they catalyze a variety of chemical reactions with stereoselectivity. These reactions include oxidation, reduction, and hydration. Examples of enzymes are oxidases, dehydrogenases, lipases, and proteases. Metoprolol, an adrenoceptor-blocking drug, is produced using an enzyme-catalyzed method. 

Generally speaking, these distinctions have not been observed by biochemists. Stereoselective has been little used, and stereospecific has been used to cover almost all aspects of the impact of stereochemical influences on reactions in living tissues or enzyme systems. Consider, for instance, the enzymatic hydration of fumarate by the enzyme, fumarase. Since there is a relationship between the structure of the substrate and product, the process could be described as stereospecific. Yet the definition of stereospecific requires that it be shown that the isomer of fumaric acid gives rise to a product which is stereochemically different from L-malate. Since the enzyme, however, does not catalyze any reaction with the (Z)-isomer (maleic acid) it is not clear whether stereospecific actually applies. 

---