Commercially viable resolution of ibuprofen.
Ibuprofen belongs to the non-steroidal anti-inflammatory drug (NSAID) family known as profens. Studies demonstrate that (S-ibuprofen is 160 times more potent than (R-ibuprofen in vitro, while the accumulation of (R-ibuprofen can cause serious side effects such as gastrointestinal pain. Candida rugosa lipase was used to enantioselectively esterify racemic ibuprofen with decan-1-ol and butan-1-ol in cyclohexane with an enantiomeric ratio (E) of 130 and 46, respectively, in up to 46% conversion. Separation by bulb-to-bulb distillation of (R)-ibuprofen and unreacted alcohol from the corresponding (S)-alkyl ibuprofen ester was possible for the decyl but not the butyl case. The enantioselective hydrolysis of (S)-alkyl ibuprofen esters with the same biocatalyst in aqueous phosphate buffer was twice as slow for the decyl alcohol versus the butyl example. The combined environmentally friendly enantioselective esterification and hydrolysis of ibuprofen insured the isolation of (S)-ibuprofen with a greater than 99% enantiomeric excess.
Chávez-Flores
David
D
Department of Chemistry, University of Texas at El Paso, 79968, USA. dabidcha@gmail.com
Salvador
James M
JM
D000438:Alcohols / Q000737:chemistry; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry* / Q000494:pharmacology*; D002175:Candida / Q000201:enzymology; D002384:Catalysis; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003510:Cyclohexanes / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004952:Esters; D006868:Hydrolysis; D007052:Ibuprofen / Q000737:chemistry* / Q000494:pharmacology*; D007700:Kinetics; D008049:Lipase / Q000737:chemistry; D008956:Models, Chemical; D010146:Pain / Q000209:etiology; D013237:Stereoisomerism
D000438:Alcohols; D000894:Anti-Inflammatory Agents, Non-Steroidal; D003510:Cyclohexanes; D004952:Esters; C506365:Cyclohexane; D008049:Lipase; D007052:Ibuprofen