Dynamic enzymatic resolution of Naproxen methyl ester in a membrane bioreactor

A lipase-catalyzed enantioselective continuous hydrolysis process under in situ racemization of substrate using sodium hydroxide as catalyst was devel oped for the production of (S)-Naproxen from racemic Naproxen methyl ester in an aqueous-organic biphase system. Use of a tubular silicone rubber memb rane in the stirred tank reactor to separate the chemical catalytic racemiz ation and biocatalytic resolution processes, served to avoid the key proble m associated with conventional dynamic resolution, viz the incompatibility of in situ chemical racemization with the presence of a biocatalyst. To ove rcome product inhibition and to facilitate product recovery from the aqueou s-organic emulsion containing substrate and lipase, a hydrophilic porous se mipermeable membrane was used in the stirred tank reactor. Greater than 60% conversion of the racemate with an enantiomeric excess of product (ee(p)) greater than 96% was obtained. In addition, transformation of Candida rugos a Lipase (CRL) isoenzymes was observed in the reaction process. (C) 2001 Society of Chemical Industry.