Recent Developments in Heterogeneous Biocatalysis

The enantiomerically pure 3-arylglutaric ester are precursors for the synthesis of (—)-paroxetine [10], a selective serotonin reuptake inhibitor used in the treatment of depression, obsessive compulsive disorder, and panic, and (i )-Baclofen [11], a GABAb receptor agonist, which is used cHnically in the treatment of spasticity (Chart 5.1). 

The 3-arylglutaric esters 3 required as substrates were obtained by condensation of 2 equiv. of ethyl acetylacetate with respective benzaldehydes, followed by hydrolysis and decarboxylation of the resulting product under basic conditions. After esterification, ester 3 was obtained in 75% overall yield (R = Cl, = Me) [10]. 

For most applications, enzymes are purified after isolation from various types of organisms and microorganisms. Unfortunately, for process application, they are then usually quite unstable and highly sensitive to reaction conditions, which results in their short operational hfetimes. Moreover, while used in chemical transformations performed in water, most enzymes operate under homogeneous catalysis conditions and, as a rule, cannot be recovered in the active form from reaction mixtures for reuse. A common approach to overcome these limitations is based on immobilization of enzymes on solid supports. As a result of such an operation, heterogeneous biocatalysts, both for the aqueous and nonaqueous procedures, are obtained. 

Enzymes are immobilized by a variety of methods. Two general types of immobilization procedures are used. The first-type procedures are based on weak interactions between the support and the enzyme and are classified as physical methods. The second-type procedures rest upon the formation of covalent bonds between the enzyme and the support and are classified as chemical methods. 

The most important physical methods are physical and ionic adsorption on a water-insoluble matrix, inclusion and gel entrapment, and microencapsulation with a liquid or a solid membrane. The most important chemical methods include covalent attachment to a water-insoluble matrix, cross-hnking with the use of a multifunctional, low-molecular weight reagent, and co-cross-linking with other neutral substances, for example proteins. 

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