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Efficient bioreductive production of (R)-N-Boc-3-hydroxypiperidine by a carbonyl reductase

Research paper by Li-Feng Chen, Yi-Ping Zhang, Hai-Yang Fan, Kai Wu, Jin-Ping Lin, Hua-Lei Wang, Dong-Zhi Wei

Indexed on: 10 Apr '17Published on: 05 Apr '17Published in: Catalysis Communications



Abstract

The 3-hydroxypiperidine moiety is a privileged scaffold encountered in many bioactive compounds. An NADPH-dependent reductase (YGL039W) from Kluyveromyces marxianus ATCC 748 was isolated to show excellent catalytic activity in (R)-N-Boc-3-hydroxypiperidine [(R)-NBHP] production. Using a GDH-catalyzed cofactor-recycling system to ensure a sufficient supply of NADPH, the effects of temperature, pH, metal ions, substrate concentration, biocatalyst dosage, and cofactors on the YGL039W-catalyzed bioreduction were investigated and optimized. Finally, an extremely high concentration of N-Boc-piperidin-3-one (NBPO, 400 g/L) could be completely reduced to (R)-NBHP (> 99% ee), with a total turnover number of 20,000. This process shows significant potential for the industrial production of (R)-NBHP.

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