Dynamic kinetic resolution of (R, S)-naproxen 2,2,2-trifluoroethyl ester via lipase-catalyzed hydrolysis in micro-aqueous isooctane

Candida rugosa lipases immobilized on polypropylene powders were employed as biocatalysts for the enantioselective hydrolysis of (R, S)-naproxen 2,2,2-trifluoroethyl ester in isooctane at 45 °C. An organic base of 1,5,7-triazabicyclo[4,4,0] dec-5-ene bound to polystyrene crosslinked with 2% DVB (p-TBD) was furthermore added as an in situ racemization catalyst for the remaining (R)-ester to carry out dynamic kinetic resolution for the racemate. The kinetic behavior of the lipase by considering enzyme stability and product inhibition and that of the base were first investigated. The results for the dynamic kinetic resolution process were then compared with those without adding p-TBD. Low enantiomeric excess (e.e.) for the product (i.e. e.e.p=58.1%) at the racemate conversion of 95.5% was obtained, which might be attributed to the decrease of racemization capacity of the base and increase of non-enzymatic hydrolysis. A comparison of the kinetic behavior was also made when employing (R, S)-naproxen 2,2,2-trifluorothioethyl ester and trioctylamine as the substrate and the base, respectively, for producing the desired (S)-naproxen.