Ibuprofen isomer conversion

Chemical reactions are used in separation processes for selective removal of components. Liquid reactive extraction and reactive distillation are examples. The solubility of reactants in supercritical gases makes available a tool to remove products from the reaction mixture. Reaction equilibrium can be shifted, and at even relatively small yields, a total conversion of educts can be achieved. Among the most selective catalysts are enzymes. These biocatalysts can selectively catalyze the reaction of one isomer. It has been shown that some enzymes are stable at high pressures and in carbon dioxide atmosphere [19]. If the reaction is carried out in a supercritical gas atmosphere and the product is soluble in the supercritical gas, a separation of the isomers is possible. As an example the separation of ibuprofen isomers will be discussed. 

Ibuprofen is an interesting case, in that the (5)-(+)-form is an active analgesic, but the ( )-(—)-enantiomer is inactive. However, in the body there is some metabolic conversion of the inactive (I )-isomer into the active (5 )-isomer, so that the potential activity from the racemate is considerably more than 50%. Box 10.11 shows a mechanism to account for this isomerism. 

The functions of chiral drugs in human body are closely related to their configurations. It has been reported that the R- and S-isomers of ibuprofen have quite different biological activities and toxicides. So it is imperative to prepare enan-tiomerically pure ibuprofen. Song el al. conducted a study on the lipase-catalyzed esterification of racemic ibuprofen with octanol in AOT reverse micelles [108,109] and found that the esterification is enantioselective and the main product is the corresponding S (-H)-ibuprofen ester, with the conversion yield and the enantiomer excess being about 36% and 0.9732, respectively. The water content and the concentration of AOT in the medium affected the conversion yield, but they had little influence on the enantiomeric excess (Table 15.7). Also, it was found that the chain lengths of alcohols affected both the rate of the reaction and the enantiomeric excess of the products. 

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