Resolution, classical using enzymic hydrolysis

Classic resolntion has been performed by formation of diastereomeiic salts which could be separated. In a series of synthetic steps and when resolution is one step, it is of utmost importance that the correct chirality is introduced at an early stage. When a racemate is subject to enzyme catalysis, one enantiomer reacts faster than the other and this leads to kinetic resolution (Figure 2.2c). Results of hydrolysis using lipase B from Candida antarctica (CALB) and a range of C-3 secondary butanoates are shown in Table 2.1. 

Enzymic resolution is also generally useful. At first sight it is of restricted applicability, since most of the classical methods are based on the selectivity of a proteinase for catalysing the hydrolysis of the l enantiomer of an A-acyl derivative of a DL-amino acid (Equation (6.7)) or of a DL-amino acid ester. The normal substrates for these enzymes are derivatives of particular coded amino acids. 

In a classical study the lipase-catalysed enantioselective hydrolysis of racemic p-nitrophenyl-2-methyldecanoate was chosen as the test reaction [15] (Fig. 8). The p-nitrophenyl ester was employed in the kinetic resolution instead of the methyl or ethyl ester, in order to make screening possible [76] (see below). The lipase from the bacterium Pseudomonas aeruginosa PAOl [77] was used as the enzyme [ 15]. The wild-type enzyme shows an enantioselectivity (ee) of only 2 % in favour of the (S)-configured 2-methyldecanoic acid, which means that the enzyme had essentially no preference for either of the enantiomeric forms. 

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