Synthesis of duloxetine intermediate (S)-3-Chloro-1-(2-thienyl)-1-propanol with liquid-core immobilized Candida pseudotropicalis 104.
(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.
Pharmaceuticals College, Zhejiang University of Technology, Hang Zhou, Zhejiang 310014, China. oozzmm@163.com
Ou
O
Zhimin
Sun
S
Xingyuan
Shi
S
Hanbing
Bi
B
Hongxia
D019149:Bioreactors / Q000382:microbiology; D002021:Buffers; D002175:Candida / Q000166:cytology* / Q000378:metabolism*; D002214:Capsules; D049109:Cell Proliferation; D018914:Cells, Immobilized / Q000378:metabolism; D048271:Chitosan / Q000737:chemistry; D000068736:Duloxetine Hydrochloride; D006863:Hydrogen-Ion Concentration; D008567:Membranes, Artificial; D008970:Molecular Weight; D010084:Oxidation-Reduction; D010710:Phosphates / Q000737:chemistry; D017680:Potassium Compounds / Q000737:chemistry; D020005:Propanols / Q000737:chemistry* / Q000378:metabolism*; D013876:Thiophenes / Q000737:chemistry* / Q000378:metabolism*
C581188:(S)-chloro-1-(2-thienyl)-1-propanol; D002021:Buffers; D002214:Capsules; D008567:Membranes, Artificial; D010710:Phosphates; D017680:Potassium Compounds; D020005:Propanols; D013876:Thiophenes; D048271:Chitosan; D000068736:Duloxetine Hydrochloride; C013216:potassium phosphate