Porcine pancreatic lipase, resolution esters

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>. 

The kinetic results for the lipase-catalysed enantioselective hydrolysis of the esters (236)-(240) can be interpreted in terms of frontier orbital localization.213 The porcine pancreatic lipase (PPL)-mediated optical resolution of 18 racemic esters can be explained by a mechanistic model involving a W-shaped active conformation of the substrate lying in a diastereo-discriminating plane.214... 

Other possibilities to prepare chiral cyanohydrins are the enzyme catalysed kinetic resolution of racemic cyanohydrins or cyanohydrin esters [107 and references therein], the stereospecific enzymatic esterification with vinyl acetate [108-111] (Scheme 2) and transesterification reactions with long chain alcohols [107,112]. Many reports describe the use of fipases in this area. Although the action of whole microorganisms in cyanohydrin resolution has been described [110-116],better results can be obtained by the use of isolated enzymes. Lipases from Pseudomonas sp. [107,117-119], Bacillus coagulans [110, 111], Candida cylindracea [112,119,120] as well as lipase AY [120], Lipase PS [120] and the mammalian porcine pancreatic lipase [112, 120] are known to catalyse such resolution reactions. 

In kinetic resolutions (Scheme 3.2-3.5) it is often the case that one of the products is required, while the other is not and must be discarded or recycled (e.g. racemised). Such operations can be wasteful or expensive. On the other hand, the biotransformation of wcso-compounds or prochiral compounds allows for the possibility of preparing an optically pure compound in quantitative yield. In Scheme 3.7, two examples of the use of meso-compounds are described. The diester (11) is made up of a complex dicarboxylic acid unit derivatised as the dimethyl ester. Pig liver esterase catalyses the hydrolysis of one of the ester groups to give the acid (12) (95% e.e.) in 96% yield. This compound is an excellent precursor of the natural product neplanocin. Note that the acid (12) is not a substrate for pie, and thus the reaction stops at the half-way stage. The compound (13), like (11), possesses a plane of symmetry. Hydrolysis catalysed by porcine pancreatic lipase (ppl) affords the alcohol (14) (>98% e.e.) in quantitative yield. The latter compound has been used to make fluorocarbocyclic adenosine (C -adenosine), a stable analogue of the naturally occurring nucleoside adenosine. 

Scheme 2.55 Resolution of epoxy esters by porcine pancreatic lipase...

---