Enzymatic resolution of (R,S)-ibuprofen and (R,S)-ketoprofen by microbial lipases from native and commercial sources

Abstract

The enantioselectivity (E) of native lipases from Aspergillus niger, Aspergillus terreus, Fusarium oxysporum, Mucor javanicus, Penicillium solitum and Rhizopus javanicus in the resolution of (R,S)-ibuprofen and (R,S)-ketoprofen enantiomers by esterification reaction with 1-propanol in isooctane was compared with known commercial Candida rugosa (Sigma) and Candida antarctica (Novozym ® 435) lipases. In the resolution of (R,S)-ibuprofen, C. rugosa lipase showed good selectivity (E = 12) while Novozym ® 435 (E = 6.7) and A. niger (E = 4.8) lipases had intermediate selectivities. Other enzymes were much less selective (E around 2.3 and 1.5), under tested conditions. After preliminary optimization of reaction conditions (water content, enzyme concentration and presence of additives) the enantioselectivity of native A. niger lipase could be enhanced substantially (E = 15). All tested lipases showed low selectivity in the resolution of (R,S)-ketoprofen because poor ester yields and low enantiomeric excess of the acid remaining were achieved.

Enantioselective esterification of ibuprofen with ethanol as reactant and solvent catalyzed by immobilized lipase: experimental and molecular modeling aspects

“…In fact, in most reports dealing with esterifications catalyzed by lipases, reactant ratios close to stoichiometric values are usually determined as the best conditions for high activity and minimal lipase inhibition. 17,18 In spite of the previous comments, assay of the commercial catalyst Novozym 435 in the esterification of racemic ibuprofen in a medium with 20 mL of ethanol resulted in high activity with only partial deactivation even after 48 h of reaction. 19 On the other hand, under the same conditions of ethanol excess Lipozyme RM IM suffered a drastic reduction in activity with almost total deactivation in the first hours of reaction (data not shown).…”

Characterization and catalytic activity of free and immobilized lipase from Aspergillus niger: a comparative study

“…1,2 The enantiomeric differentiation of lipases is used to separate racemic mixtures of chiral esters, hydrolyzing preferentially one enantiomer or through esterification reactions of chiral acids and/or chiral alcohols. The versatility of these biocatalysts, when used in organic solvents, allows attainment of a great variety of other pharmaceutical intermediates.…”

Kinetic analysis of batch ethanol acetylation in isothermal non-stationary multiphase systems by lyophilized mycelium of Aspergillus oryzae

“…From the experimental results obtained under the optimal conditions, we then estimated the values of the parameters k 1 and E o listed in Table 1. As it can be seen, the values of k 1 are comparable one to the other, while those of the concentration of the active free enzyme are nearly proportional to the ones of the mycelium used in the runs.…”