Stereoselective synthesis of (S)-(+)-Naproxen catalyzed by carboxyl esterase in a multicompartment electrolyzer.
The stereoselective hydrolysis of racemic 2-substituted propionates, catalyzed by carboxyl esterase, provides a cost-competitive route to produce the optically pure, anti-inflammatory drug Naproxen. In the present work, we describe the application of the multicompartment electrolyzer reactor (ME) for the stereoselective hydrolysis of a racemic Naproxen ester, (R,S)-ethoxyethyl-[2-(6-methoxy-2-naphtyl)]propionate, catalyzed by a carboxyl esterase. The enzyme was trapped in a reactor chamber, delimited by two isoelectric membranes encompassing the pI value of the enzyme, together with the neutral substrate. After 90 min, a conversion of 45% was obtained with an enantiomeric excess of 84%. The reaction product, (S)-(+)-Naproxen, was electrophoretically removed in continuous from the reaction chamber and collected in a contiguous, more acidic chamber, separated from the enzyme and from the unreacted substrate. Moreover, at the end of the reaction, it was possible to recover the enzyme from the reactor and use it again.
Cretich
M
M
Institute of Biocatalysis and Molecular Recognition, CNR, Via Mario Bianco, 9, 20131, Milan, Italy.
Chiari
M
M
Carrea
G
G
D001671:Biochemistry / Q000191:economics / Q000379:methods; D002265:Carboxylic Ester Hydrolases / Q000378:metabolism*; D002384:Catalysis; D002462:Cell Membrane; D019075:Electrophoresis, Capillary; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008956:Models, Chemical; D009288:Naproxen / Q000138:chemical synthesis* / Q000737:chemistry*; D013237:Stereoisomerism; D013997:Time Factors
D009288:Naproxen; D002265:Carboxylic Ester Hydrolases