Biotransformations for the production of the chiral drug (S)-Duloxetine catalyzed by a novel isolate of Candida tropicalis.
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 degrees 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%.
Soni
Pankaj
P
Biocatalysis Laboratory, Department of Pharmaceutical Technology, National Institute of Pharmaceutical Education and Research, Sector 67, S.A.S. Nagar, 160 062, India.
Banerjee
U C
UC
D001673:Biodegradation, Environmental; D041022:Candida tropicalis / Q000254:growth & development / Q000302:isolation & purification / Q000378:metabolism*; D002482:Cellulose / Q000031:analogs & derivatives; D000068736:Duloxetine Hydrochloride; D006863:Hydrogen-Ion Concentration; D011437:Propylamines / Q000737:chemistry / Q000378:metabolism; D012988:Soil Microbiology; D013696:Temperature; D013876:Thiophenes / Q000378:metabolism*
D011437:Propylamines; D013876:Thiophenes; C070231:Chiracel OJ; D002482:Cellulose; D000068736:Duloxetine Hydrochloride