Enzyme resolution, prochiral diester

Figure 2.2 Production of enantiopure compounds using hydrolytic enzymes. In (a) a prochiral diester is hydrolysed to yield predominance (in theory 100%) of one enantiomer. In the next example (b) a raeso-diester is hydrolysed to yield predominance (in theory 100%) of one enantiomer of the monoester. If kj>k2 the (IS, 2i )-enantiomer is formed to the greatest extent. Due to the preference of the enzyme k4>kj and the lower monoester (IR, 2S) will be removed fastest. Hence both steps will lead to an increase of the upper enantiomer at the monoester stage. If the reaction proceeds to completion, however, the result will be another raeio-compound, a diol. In example (c) a racemic secondary ester is resolved by hydrolysis. One monoester is hydrolysed faster than the other and this leads to kinetic resolution.

In the 1980 s there was a great increase in the development and use of enzymatic procedures by synthetic chemists.6 Previously regarded more as scientific curiosities of limited scope than of practical utility, biological-chemical transformations are now used regularly by synthetic chemists. The ability to induce optical activity in molecules where none existed before is the most useful property of these chiral catalysts. Hydrolase enzymes are generally preferred over other kinds of enzymes for transformations of this nature because they are more easily handled and do not require cofactors for activity. In cases where enantiotopic differentiation between ester functions is desired, prochiral meso diesters are more efficient substrates than racemic esters. In the former case it is possible for all starting material to be converted into a single enantiomer, whereas in the latter example only enzymatic resolution is possible. 

Scheme 2.13 shows a few examples of resolutions and desymmetrization using esterases. Entry 1 shows the partial resolution of a chiral ester using a crude enzyme source. The enantioselectivity is only moderate. Entries 2 to 5 are examples of desymmetrization, in which prochiral ester groups are selectively hydrolyzed. Entries 6 and 7 are examples of selective hydrolysis of unsaturated esters that lead to isomeric monoesters. These cases are examples of diastereoselectivity. In Entry 8, the f ,f -enantiomer of a racemic diester is selectively hydrolyzed. In all these cases, the... 

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