Enhancement of enantioselectivity and reaction rate on the synthesis of (S)-ketoprofen hydroxyalkyl ester in organic solvents via isopropanol-dried immobilized lipase

Abstract

Lipase-catalyzed enantioselective esterification between (R,S)-ketoprofen and alkanediol in organic solvents was developed to produce (S)-ketoprofen hydroxyalkyl esters. The acyl acceptor of 1,6-hexanediol for the resolution of (R,S)-ketoprofen yielded only the enantioselectivity (the enantiomeric ratio of initial rate for (S)-ketoprofen to that of (R)-ketoprofen) VS/VR = 8, when crude Lipase MY originating from Candida rugosa was used. However, isopropanol-dried immobilized lipases (IPA-dried IM-lipase) effectively enhanced the enantioselectivity to greater than 20 in the esterification of (R,S)-ketoprofen when 1,4-butanediol, 1,5-pentanediol or 1,6-hexanediol was employed. IPA-dried IM-lipase and isooctane were selected to use for optimally immobilized lipase and reaction medium, respectively. The IPA-dried IM-lipase exhibited the highest enantioselectivity, E = 26.7, to the (S)-enantiomer with 1,5-pentanediol and the best enzyme activity to the (S)-enantiomer with 1,4-butanediol. The finding indicates that the carbon chain length of the alkanediol strongly affected the enzyme activity and enantioselectivity of lipase-catalyzed esterification. A maximum enantioselectivity of 37 at 27 °C was generated by IPA-dried IM-lipase for the enantioselective esterification of racemic ketoprofen with 1,4-butanediol. IPA-dried IM-lipase can effectively increase the enantioselectivity of lipase. Copyright © 2005 Society of Chemical Industry