Hydrolase chemoselectivity

An unusual case of intramolecular competition (chemoselectivity, see Chapt. 1 in [la]) between ester and oxirane occurs in the detoxification of (oxiran-2-yl)methyl 2-ethyl-2,5-dimethylhexanoate (10.49), one of the most abundant isomers of an epoxy resin. The compound is chemically very stable, i.e., resistant to aqueous hydrolysis, but is rapidly hydrolyzed in cytosolic and microsomal preparations by epoxide hydrolase and carboxylesterase, which attack the epoxide and ester groups, respectively [129], The rate of overall enzymatic hydrolysis was species dependent, decreasing in the order mouse > rat > human, but was relatively fast in all tissues examined (lung and skin as portals of entry, and liver as a further barrier). In mouse and rat lung microsomes, ester hydrolysis was 3-4 times faster than epoxide hydration, whereas the opposite was true in human lung microsomes. 

Hydrolase-catalyzed enantioselective N-acylation is an important tool for the preparation of enantiopure a- and P-aminoacids. It has been observed that the reactions of many amino acid esters with ester acyl donors catalyzed by CALB is sometimes complicated by interesterification reactions. CALA has, however, emerged as a very chemoselective catalyst in favor of N-acylation of P-aminoesters. Some reviews on CALA and other hydrolases as catalysts for N-acylations of aminoesters are available [109, 126, 127]. 

Enzyme-catalysed hydrolysis and esterification reactions are the most commonly exploited biotransformations. There are two main reasons for this state of affairs. Firstly, the reactions are very easy to perform, and no special apparatus is required. Secondly, there is a wide range of hydrolase enzymes available from commercial suppliers. Furthermore, the stereoselectivities and chemoselectivities of the enzymes are well known, and the likely stereochemical outcomes of such enzyme-catalysed reactions on previously unused substrates are now becoming predictable. 

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