Ultrasound promoted enantioselective transesterification of 3-hydroxy-3-(2-thienyl) propanenitrile catalyzed by lipase

Abstract

(S)-3-hydroxy-3-(2-thienyl) propanenitrile, which is the key chiral building block for the synthesis of (S)-duloxetine, was successfully prepared via enantioselective transesterification catalyzed by lipase under ultrasound irradiation. Compared with conventional shaking, the enzyme activity and enantioselectivity were dramatically enhanced under ultrasound irradiation. Under optimum reaction conditions (solvent: n-hexane, ultrasound power: 150 W, aw: 0.33, temperature: 40°C), Pseudomonas sp. lipase exhibited an excellent catalytic performance (enzyme activity: 81.5 μmol g−1 min−1, E-value: 65.4). The reaction achieved its equilibrium in approximately 7 h with a conversion of 53.9% and high enantiopurity (99% ee) of (S)-3-hydroxy-3-(2-thienyl) propanenitrile could be obtained.

Keywords

• 3-Hydroxy-3-(2-thienyl) propanenitrile
• lipase
• resolution
• ultrasound