Prochiral diester, desymmetrization

Desymmetrization of Prochiral Diesters. PLE has been used only relatively infrequently for the resolution of racemic esters, while a-chymotrypsin has played... 

Esterases, proteases, and some lipases are used in stereoselective hydrolysis of esters bearing a chiral or a prochiral acyl moiety. The substrates are racemic esters and prochiral or meso-diesters. Pig liver esterase (PLE) is the most useful enzyme for this type of reaction, especially for the desymmetrization of prochiral or meso substrates. 

The first asymmetric synthesis of (—)-Y-jasmolactone, a fruit fiavor constituent, vas achieved via the enantioselective lactonization (desymmetrization) of a prochiral hydroxy diester promoted by porcine pancreas lipase (PPL) (Figure 6.23) [71]. 

Reaction in organic solvent can sometimes provide superior selectivity to that observed in aqueous solution. For example, Keeling et al recently produced enantioenriched a-trifluoromethyl-a-tosyloxymethyl epoxide, a key intermediate in the synthetic route to a series of nonsteroidal glucocorticoid receptor agonist drug candidates, through the enan-tioselective acylation of a prochiral triol using the hpase from Burkholderia cepacia in vinyl butyrate and TBME (Scheme 1.59). In contrast, attempts to access the opposite enantiomer by desymmetrization of the 1,3-diester by lipase-catalysed hydrolysis resulted in rapid hydrolysis to triol under a variety of conditions. 

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... 

As shown in Scheme 2.27, the prochiral center may be moved from the site of the reaction into the (3-position. Thus, chiral recognition by PLE [214-218] and a-chymotrypsin [219-222] is retained during the desymmetrization of prochiral 3-substituted glutaric diesters. Whole cells of Acinetobacter lowfii and Arthrobac-ter spp. have also been used as a source for esterase activity [223] and, once again, depending on the substitutional pattern on carbon-3, the desymmetrization can lead to both enantiomeric products. 

Resolution of Racemic Esters. Although PLE-catalyzed resolution of racemic esters have been performed less often as compared to the desymmetrization of prochiral and me,so-diesters, it can be a valuable technique. 

Scheme 2.54 Desymmetrization of prochiral 1,3-propanediol diesters by porcine pancreatic...

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