Porcine pancreatic lipase asymmetric hydrolysis

Kinetic resolutions by means of the selective formation or hydrolysis of an ester group in enzyme-catalyzed reactions proved to be a successful strategy in the enantioseparation of 1,3-oxazine derivatives. Hydrolysis of the racemic laurate ester 275 in the presence of lipase QL resulted in formation of the enantiomerically pure alcohol derivative 276 besides the (23, 3R)-enantiomer of the unreacted ester 275 (Equation 25) <1996TA1241 >. The porcine pancreatic lipase-catalyzed acylation of 3-(tu-hydroxyalkyl)-4-substituted-3,4-dihydro-2/7-l,3-oxazines with vinyl acetate in tetrahydrofuran (THF) took place in an enantioselective fashion, despite the considerable distance of the acylated hydroxy group and the asymmetric center of the molecule <2001PAC167, 2003IJB1958>. 

Enantiomerically pure cyclopropanes are a frequent motif in the structure of natural products. Their synthesis is often demanding and many approaches have been made [50, 51]. Porcine pancreatic lipase (PPL) was used for the stereoselective desymmetrization of a cyclopropane dibutanoate (Fig. 2). The asymmetric hydrolysis of the meso compound yielded the corresponding enantiopure alcohol almost quantitatively. The intermediate obtained was successfully applied in the total synthesis of dictyopterenes A and C, sexual pheromones of brown algae [52], and constanolactones (see below) [53]. 

The 5 -(-)-2-cyclohexy 1-1,3-propanediol monoacetate (24) and the S-( )-2-phenyl-1,3-propanediol monoacetate (25) are key chiral intermediates for the chemoenzymatic synthesis of Monopril (26) (Fig. 10), a new antihypertensive drug which acts as an ACE inhibitor. The asymmetric hydrolysis of 2-cyclohexyl-1,3-propanediol diacetate (27) and 2-phenyl-1,3-propanediol diacetate (28) to the corresponding S-( - )-monoacetate (24) and S-( )-monoacetate (25) by porcine pancreatic lipase (PPL) and Chromobacterium viscosum lipase have been demon-... 

Selected prochiral and meso-substrates have been used with various esterases and lipases (Figure 2) and illustrate the wide variety of substrates that can be used with these enzymes. A complete listing of these types of substrates can be found in other sources [12,105,107,120,121]. It should be noted that the use of organic solvent can have a profound effect as to what product isomer is formed [127]. The use of porcine pancreatic lipase (PPL) to carry out an asymmetric hydrolysis of a meso-diacetate for the production of an intermediate in pheromone synthesis was recently reported [128]. Two specific examples are discussed here that used this approach directed at key chiral pharmaceutical intermediates. 

Scheme 2.53 Asymmetric hydrolysis of cyclic meso-diacetates by porcine pancreatic lipase...

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