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Highly enantioselective bioreduction of N-methyl-3-oxo-3-(thiophen-2-yl) propanamide for the production of (S)-duloxetine

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Abstract

Whole cells of Rhodotorula glutinis reduced N-methyl-3-oxo-3-(thiophen-2-yl) propanamide at 30 g/l to (S)-N-methyl-3-hydroxy-3-(2-thienyl) propionamide, an intermediate in the production of (S)-duloxetine, a blockbuster antidepressant drug, in 48 h. The reaction had excellent enantioselectivity (single enantiomer, >99.5% enantiomeric excess [ee]) with a >95% conversion.

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Acknowledgments

This work was supported by the 100 Talents Program, the West Light Foundation, and the Knowledge Innovation Program (KSCX2-YW-G-075) of the Chinese Academy of Sciences, and National Natural Science Foundation of China (20802073 & 21072183).

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Correspondence to Zhong-Liu Wu.

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Tang, CG., Lin, H., Zhang, C. et al. Highly enantioselective bioreduction of N-methyl-3-oxo-3-(thiophen-2-yl) propanamide for the production of (S)-duloxetine. Biotechnol Lett 33, 1435–1440 (2011). https://doi.org/10.1007/s10529-011-0578-8

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  • DOI: https://doi.org/10.1007/s10529-011-0578-8

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