Abstract
A yeast strain, Candida tropicalis PBR-2, isolated from soil, is capable of carrying out the enantioselective reduction of N,N-dimethyl-3-keto-3-(2-thienyl)-1-propanamine to (S)-N,N-dimethyl-3-hydroxy-3-(2-thienyl)-1-propanamine, a key intermediate in the synthesis of the chiral drug (S)-Duloxetine. The organism produced the enantiopure (S)-alcohol with a good yield (>80%) and almost absolute enantioselectivity, with an enantiomeric excess (ee) >99%. Parameters of the bioreduction reaction were optimized and the optimal temperature and pH for the reduction were found to be 30°C and 7.0, respectively. The optimized substrate and the resting cell concentration were 1 g/l and 250 g/l, respectively. The preparative-scale reaction using resting cells of C. tropicalis yielded the (S)-alcohol at 84–88% conversion and ee >99%.
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Acknowledgements
We are grateful to Dr. A.K. Chakraborati for helpful discussions. P.S. gratefully acknowledges the Council of Scientific and Industrial Research, India, for providing a Junior Research Fellowship
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Soni, P., Banerjee, U.C. Biotransformations for the production of the chiral drug (S)-Duloxetine catalyzed by a novel isolate of Candida tropicalis. Appl Microbiol Biotechnol 67, 771–777 (2005). https://doi.org/10.1007/s00253-004-1870-5
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DOI: https://doi.org/10.1007/s00253-004-1870-5