Kinetic resolution of (R, S)-2-(2-chloro-1-hydroxyethyl) thiophene via immobilizing lipase from Alcaligenes sp. onto magnetic nanoparticles

Abstract

BACKGROUND: (S)-2-(2-chloro-1-hydroxyethyl) thiophene is one of the most important intermediates for the synthesis of (S)-duloxetine. The preparation of (S)-2-(2-chloro-1-hydroxyethyl) thiophene could be realized from its racemate via enzymatic resolution. This study aimed to prepare an easy-recycling immobilized lipase with excellent performance and use it to obtain (S)-2-(2-chloro-1-hydroxyethyl) thiophene with high enantiometric purity through enzymatic enantioselective transesterificaion in organic media. To achieve this, immobilization of the lipase and the effects of different reaction conditions (e.g. organic solvent, water activity, substrate ratio and temperature) on the activity and enantioselectivity of the lipase were investigated. RESULTS: Lipase from Alcaligenes sp. (lipase QL) was successfully immobilized onto the prepared magnetic Fe3O4 nanoparticles through hydrophobic interaction, and the enzyme loading (97.4±2.3 mg g-1) as well as immobilization yield (48.7±1.4%) was obtained. Under optimum reaction conditions, the higher enzyme activity (0.225±0.01 μmol mg-1 min-1) and enantioselectivity (E-value: 59.7±1.8) for the immobilized lipase QL than those (enzyme activity: 0.034±0.002 μmol mg-1 min-1, E-value: 57.9±2.0) for aggregated lipase was observed. The results also showed that (S)-2-(2-chloro-1-hydroxyethyl) thiophene with optical purity ≥99% was obtained. In addition, the immobilized lipase QL was easily separated from the reaction media by magnetic steel, and maintained 90% of its initial activity with nearly unchanged enantioselectivity after five consecutive cycles. CONCLUSION: The results obtained demonstrated good potential for practical application of magnetic nanoparticle-immobilized lipase for the resolution of 2-(2-chloro-1-hydroxyethyl) thiophene through enantioselective transesterification.