Dual Mechanoenzymatic Kinetic Resolution of (±)‐Ketorolac

• Published in: ChemCatChem
• Main Authors: Pérez‐Venegas, Mario, Rodríguez‐Treviño, Agustín Mario, Juaristi, Eusebio
• Format: Article in Journal/Newspaper
• Language: English
• Published: Wiley 2020
• Subjects: Antarc*; Antarctica
• Online Access: http://dx.doi.org/10.1002/cctc.201902292; https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fcctc.201902292; https://onlinelibrary.wiley.com/doi/pdf/10.1002/cctc.201902292; https://onlinelibrary.wiley.com/doi/full-xml/10.1002/cctc.201902292

Abstract Recently, biocatalysis mediated by mechanical energy has become a convenient strategy to obtain highly valuable products following the principles of green chemistry. In particular, mechanoenzymatic techniques have allowed the isolation of chiral drugs with high enantiomeric purity. In this regard, being aware of the preponderant anti‐inflammatory activity of Ketorolac's ( S )‐isomer relative to its ( R )‐enantiomer, we developed a mechanoenzymatic kinetic resolution protocol using Candida antarctica Lipase B to yield both enantiomers with high enantiopurity. The significant enantiopreference of CALB for the ( R )‐isomer of Ketorolac allowed the isolation of the active ( S )‐enantiomer, either by means of an enantioselective esterification of racemic Ketorolac or via enantioselective hydrolysis of suitable ester derivatives. Both techniques proceeded in short reaction times, with high enantiomeric excess (>83 %), remarkable enantiodiscrimination ( E ≫500) and rather good conversion (46 %). Furthermore, ( R )‐Ketorolac, an effective drug for ovarian cancer management, was obtained in essentially enantiopure form ( ee >99 %).