Search

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. © 2014 Society of Chemical Industry

BACKGROUND: The enantiomers of N-hydroxymethyl vince lactam are important intermediates during the synthesis of chiral drugs. The preparation of its single enantiomer can be performed through enzymatic resolution. The aim of this work is to obtain (1S ,4 R)-N-hydroxymethyl vince lactam with high enantiomeric purity via lipase-catalyzed enantioselective transesterification in organic solvents. To achieve this, effects of various reaction conditions (including lipase sources, acyl donor, substrate molar ratio, organic solvent, temperature, and water activity) on the enzyme activity as well as enantioselectivity were investigated. RESULTS: The results of the study showed that the enantiopreference for all the selected enzymes was (4S ,1 R)-N-hydroxymethyl vince lactam in enantioselective transesterification of racemic N-hydroxymethyl vince lactam. Under the selected optimum conditions, the highest enantioselectivity (E = 33.8) was obtained with a higher enzyme activity (20.3 µmol g −1 min −1 )f or Mucor miehei lipase (MML) when vinyl valerate was used as the acyl donor. Besides, the remained (1S ,4 R)-N-hydroxymethyl vince lactam with high enantiomeric purity (ee > 99%) was obtained when the conversion was about 60%. CONCLUSION: The results obtained clearly demonstrated potential for industrial application of lipase in resolution of N-hydroxymethyl vince lactam through enantioselective transesterification. c � 2012 Society of Chemical Industry