Resolution of racemic flurbiprofen by lipase-mediated esterification in organic solvent

✍ Scribed by Raffaele Morrone; Giovanni Nicolosi; Angela Patti; Mario Piattelli

• Publisher: Elsevier Science
• Year: 1995
• Tongue: English
• Weight: 357 KB
• Volume: 6
• Category: Article
• ISSN: 0957-4166
• DOI: 10.1016/0957-4166(95)00223-c

✦ Synopsis

Resolution of rac-flurbiprofen, 2-fluoro-0t-methyi-[1,1'-biphenyl]-4-scetic acid (1), by biocatalytic methodologies has been studied. Enzymatic hydrolysis of rac-flurbiprofen methyl ester (2) in aqueous-organic medium gave poor results. Transesterification of the same ester mediated by immobilized lipase from Candida antarctica (Novozym ® 435) in organic solvent proceeded with good enantiomeric excess but the isolation of the product required chromatographic separation and therefore was unsuitable for large scale preparation. Direct esterification of 1 with methanol in aeetonitrile promoted by Novozym ® 435 proved to be the best method since it gave, via a twofold kinetic resolution, S-flurbiprofen with excellent enantiomeric excess. The R-flurbiprofen methyl ester formed in the reaction can be converted into the starting rac-flurbiprofen by alkaline hydrolysis or, alternatively, into R-flurbiprofen by hydrolysis with acid.