Chemo-enzymatic synthesis of optically active polymeric prodrug of naproxen, ketoprofen and ibuprofen

A combined enzymatic resolution and chemical polymerization strategy has been used to create optically active polymeric prodrugs. (S)-Naproxen, (S)-ketoprofen and (S)-ibuprofen derivatives were obtained in excellent optical purity and high yield by enzymatic resolution after optimization of reaction conditions. Each optically active monomer was subjected to free radical polymerization with methyl methacrylate. The obtained optically active polymeric prodrugs bearing (S)-naproxen, (S)-ketoprofen or (S)-ibuprofen residue were characterized by IR, NMR and GPC. The effect of molar ratio of naproxen vinyl ester to methyl methacrylate on the polymerization was also investigated. This methodology is useful to provide a facile and clean route to optically active macromolecular prodrugs.