The preparation of polymerizable, optically active non-steroidal anti-inflammatory drugs derivatives by irreversible enzymatic methods

A lipase-catalyzed irreversible resolution of 2-arylpropionic acids was developed using the corresponding racemic vinyl esters as activated substrates. The obtained products, (S)-ketoprofen vinyl ester, (S)-naproxen vinyl ester and (S)-ibuprofen vinyl ester would be useful as significant monomers for polymeric drug. The effect of enzyme sources, solvent, water amount and temperature on the hydrolysis resolution was investigated. Optically active, polymerizable ketoprofen prodrug can be obtained with excellent enantioselectivity (ee ∼ 90%) after optimization of the reaction conditions. Lipased-catalyzed transesterification of (R,S)-ketoprofen vinyl esters with various alcohols was also studied. The use of vinyl ester effectively enhanced the enantioselectivity compared with other common ester, such as ethyl and butyl esters.