Kinetic Resolution of Profens by EnantioselectiveEsterification Catalyzed by Candida antarctica and Candida rugosa Lipases

Abstract

Profens (2-arylpropionic acids) are known as one of the major nonsteroidal antiinflammatory drugs (NSAIDs) used in the treatment of inflammation associated with tissue injury. The inflammatory activity of profens is mainly due to their (S)-enantiomer, whereas they are commercially available not only as pure enantiomers, but as racemates as well. There are several methods widely used in order to obtain enantiomerically pure compounds, however, the kinetic resolution with the application of lipases as biocatalysts may have an added advantage in the production of optically pure active pharmaceutical ingredients, such as milder reaction conditions, reduced energy requirements, and production costs. The aim of this study was to compare the results described in the literature in the case of the influence of reaction medium, alcohol moiety, and reaction temperature on the catalytic activity of lipases from Candida antarctica and Candida rugosa.

Enantioseparation of flurbiprofen enantiomers using chiral ionic liquids by liquid‐liquid extraction

“…[12][13][14] Nevertheless, the resolution of the racemate is relatively simple and it is possible to obtain two enantiomers simultaneously, which need to be considered. 15,16 Most of the resolution methods, such as crystallization, [17][18][19] kinetic resolution method, [20][21][22] chromatographic resolution method, 23 membrane separation method, 24 etc., are difficult to achieve industrialization due to low capacity and narrow application range. Chromatography and electrochemical methods are mainly used for the analysis of enantiomers, currently.…”

Advances in Recombinant Lipases: Production, Engineering, Immobilization and Application in the Pharmaceutical Industry

“…The anti-inflammatory activity of ketoprofen, flurbiprofen, ibuprofen, and naproxen is mainly related to their (S)-enantiomer. For these drugs, (R)-enantiomers contribute weakly to cyclooxygenase (COX) inhibition and have been related to side effects-e.g., gastrointestinal pain [163,164].…”

“…In recent years, the kinetic resolution of 2-arylpropionic acids by enantioselective esterification has been widely studied. Lipases have been applied in this process and their relevant characteristics demonstrated in many papers; the promising results point to the future applications of these enzymes [5,6,164,165]. For instance, lipases from C. antarctica, C. rugosa [164,166] and A. niger [6] have been applied in the kinetic resolution of profens, making it possible to obtain drugs with high enantiomeric purity-e.g., (R)-flurbiprofen, ee p = 96.3%; E = 90.5%; C = 35.7%), therefore, demonstrating their great potential as biocatalysts in pharmaceutical synthesis.…”

Optimized hybrid nanospheres immobilizing Rhizomucor miehei lipase for chiral biotransformation

“…The catalytic performance and the stability of optimized heterogeneous catalysts was evaluated in a enantioselective esterification of racemic ibuprofen (Figure 1), in order to produce active enantiomer from racemic product. In the last year, there was an increasing trend toward the use of Lipase for a production of enantiomerically pure compounds [39][40][41][42][43][44][45][46][47][48], particularly in a chiral resolution of (R,S)-ibuprofen [49][50][51][52][53][54][55][56][57][58][59]. In particularly, Immobilized Rhizomucor miehei lipase shows to have adequate stability and biosynthetic capabilities for a chiral resolution of (R,S)ibuprofen [60][61][62].…”