Synthesis of duloxetine intermediate (S)-3-Chloro-1-(2-thienyl)-1-propanol with liquid-core immobilized candida pseudotropicalis 104

摘要

(S) -3-Chloro-1-(2-thienyl)-1-propanol was synthesized by the asymmetric reduction of 3-chloro-1-(2-thienyl)propanone with liquid-core immobilized Candida pseudotropicalis 104. The optimum time was 28 h for the re-cultivation of immobilized cells. The optimum film solvent for the liquid-core capsule was 0.3 % chitosan (M_w 1.0 × 10~5). Conversion decreased with the increase of the liquid-core capsule diameter and with the addition of more substrates at the same reduction time. The immobilized cells show good reduction ability in a potassium phosphate buffer (pH 6.6~7.2). The material outside the spread speed of immobilized cells was not restricted when the shaking speed was higher than 160 r/min. Liquid-core immobilized cells can be reused 11 times. Compared with the batch reduction, the continuous reduction of 3-chloro-1-(2-thienyl)propanone in the membrane reactor with liquid-core immobilized cells as catalyst can relieve the inhibition from a high-concentration substrate. Conversion and enantiometric excess of (S)-3-chloro-1-(2-thienyl)-1-propanol reached 100 % and 99 % in a continuous reduction of 12 g/L 3-chloro-1-(2-thienyl)propanone for 10 days.