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

Appl Biochem Biotechnol. 2012 Dec;168(8):2297-308. doi: 10.1007/s12010-012-9938-7. Epub 2012 Oct 16.

Abstract

(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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bioreactors / microbiology
  • Buffers
  • Candida / cytology*
  • Candida / metabolism*
  • Capsules
  • Cell Proliferation
  • Cells, Immobilized / metabolism
  • Chitosan / chemistry
  • Duloxetine Hydrochloride
  • Hydrogen-Ion Concentration
  • Membranes, Artificial
  • Molecular Weight
  • Oxidation-Reduction
  • Phosphates / chemistry
  • Potassium Compounds / chemistry
  • Propanols / chemistry*
  • Propanols / metabolism*
  • Thiophenes / chemistry*
  • Thiophenes / metabolism*

Substances

  • (S)-chloro-1-(2-thienyl)-1-propanol
  • Buffers
  • Capsules
  • Membranes, Artificial
  • Phosphates
  • Potassium Compounds
  • Propanols
  • Thiophenes
  • Chitosan
  • Duloxetine Hydrochloride
  • potassium phosphate