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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

Triptorelin lactate was successfully synthesized by porcine pancreatic lipase (PPL) in organic solvents. The effects of acyl donor, substrate ratio, organic solvent, temperature, and water activity were investigated. Under the optimum conditions, a yield of 30% for its ester could be achieved in the reaction for about 48 h.

Aeropyrum pernix esterase (APE1547) was successfully used to catalyze the enantioselective transesterification of (R/S)-2-methyl-1-butanol in an ionic liquid (IL). Effects of various reaction conditions on the synthetic activity of the enzyme as well as enantioselectivity, including the type of IL, acyl donor, temperature, water activity, and substrate molar ratio were inverstigated. APE1547 showed good catalytic performance (activity > 0.8 μmol/min/mg, E > 25), and the enzyme-IL mixture was recycled five times with only a slight decrease in catalytic performance.

The lipase from Pseudomonas fluorescens (Lipase AK, AKL) was immobilized onto the magnetic Fe3O4 nanoparticles via hydrophobic interaction. Enzyme loading and immobilization yield were determined as 21.4 ± 0.5 mg/g and 49.2 ± 1.8 %, respectively. The immobilized AKL was successfully used for resolution of 2-octanol with vinyl acetate used as acyl donor. Effects of organic solvent, water activity, substrate ratio, and temperature were investigated. Under the optimum conditions, the preferred isomer for AKL is the (R)-2-octanol and the highest enantioselectivity (E = 71.5 ± 2.2) was obtained with a higher enzyme activity (0.197 ± 0.01 μmol/mg/min). The results also showed that the immobilized lipase could be easily separated from reaction media by the magnetic steel and remained 89 % of its initial activity as well as the nearly unchanged enantioselectivity after five consecutive cycles, indicating a high stability in practical operation.