ENANTIOSELECTIVE SYNTHESIS OF IBUPROFEN ESTERS IN AOT ISOOCTANE MICROEMULSIONS BY CANDIDA-CYLINDRACEA LIPASE

The enantioselective esterification of racemic ibuprofen, catalyzed by a Candida cylindracea lipase, was studied in a water-in-oil microemul sion (AOT/isooctane). By using n-propanol as the alcohol, an optimal w 0 ([H2O]/[AOT] ratio) of 12 was found for the synthesis of n-propyl-ib uprofenate at room temperature. The lipase showed high preference for the S(+)-enantiomer of ibuprofen, which was esterified to the correspo nding S(+)-ibuprofen ester. The R(-)-ibuprofen remained unesterified i n the microemulsion. The calculated enantioselectivity value (E) for S -ibuprofen ester was greater than 150 (conversion 0.32). The enzyme ac tivities of n-alcohols with different chain lengths (3-12) were compar ed, and it appeared that short- (propanol and butanol) and long-chaine d (decanol and dodecanol) alcohols were better substrates than the int ermediate ones (pentanol, hexanol, and octanol). However, unlike secon dary and tertiary alcohols, all of the tested primary alcohols were su bstrates for the lipase. The reversible reaction (i.e., the hydrolysis of racemic ibuprofen ester in the microemulsion) was also carried out enantioselectively by the enzyme. Only the S form of the ester was hy drolyzed to the corresponding S-ibuprofen. The reaction yield was, how ever, only about 4% after 10 days of reaction. The corresponding yield for the esterification of ibuprofen was about 35% (10 days). The high enantioselectivity displayed by the lipase in the microemulsion syste m was seen neither in a similar esterification reaction in a pure orga nic solvent system (isooctane) nor in the hydrolysis reaction in an aq ueous system (buffer). The E value for S-ibuprofen ester in the isooct ane system was 3.0 (conversion 0.41), and only 1.3 for S-ibuprofen in the hydrolysis reaction (conversion 0.32). The differences in enantios electivity for the lipase in various systems are likely due to interfa cial phenomena. In the microemulsion system, the water in which the en zyme is dissolved is separated from the solvent by a layer of surfacta nt molecules, thus creating an interface with a relatively large area, Such interfaces are not present in the pure organic solvent systems ( no surfactant) nor in aqueous systems. (C) 1993 John Wiley & Sons, Inc .