Abstract
Duloxetine intermediate (S)-(-)-3-N-methylamino-1-(2-thienyl)-1-propanol was synthesized using ACA liquid-core immobilized Saccharomyces cerevisiae CGMCC No. 2230. The optimum culture time for ACA liquid-core immobilized cells was found to be 28 h. The optimum ACA liquid-core capsule formation conditions were found to be 90% chitosan deacetylation, 30,000-50,000 chitosan molecular weight, 5.0 g/L chitosan, and pH 6.0 citrate buffer solution. The highest activity was found when reduction conditions were pH 6.0, 30 °C and 180 rpm. The ACA-immobilized cells can be reused nine times and only 40% of the activity is retained after nine cycles. Product inhibition of reduction was observed in batch reduction. Continuous reduction in the membrane reactor was found to remove the product inhibition on reduction and improve production capacity. Conversion reached 100% and enantiometric excess of (S)-(-)-3-N-methylamino-1-(2-thienyl)-1-propanol exceeded 99.0% in continuous reduction of 5 g/L 3-N-methylamino-1-(2-thienyl)-1-propanone in the membrane reactor.
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