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Efficient enantioselective synthesis of (R)-[3,5-bis(trifluoromethyl)phenyl] ethanol by Leifsonia xyli CCTCC M 2010241 using isopropanol as co-substrate.
J Microbiol Biotechnol 2013; 23(3):343-50JM

Abstract

(R)-[3,5-Bis(trifluoromethyl)phenyl] ethanol is a key chiral intermediate for the synthesis of aprepitant. In this paper, an efficient synthetic process for (R)-[3,5- bis(trifluoromethyl)phenyl] ethanol was developed via the asymmetric reduction of 3,5-bis(trifluoromethyl) acetophenone, catalyzed by Leifsonia xyli CCTCC M 2010241 cells using isopropanol as the co-substrate for cofactor recycling. Firstly, the substrate and product solubility and cell membrane permeability of biocatalysts were evaluated with different co-substrate additions into the reaction system, in which isopropanol manifested as the best hydrogen donor of coupled NADH regeneration during the bioreduction of 3,5-bis(trifluoromethyl) acetophenone. Subsequently, the optimization of parameters for the bioreduction were undertaken to improve the effectiveness of the process. The determined efficient reaction system contained 200 mM of 3,5-bis(trifluoromethyl) acetophenone, 20% (v/v) of isopropanol, and 300 g/l of wet cells. The bioreduction was executed at 30°C and 200 rpm for 30 h, and 91.8% of product yield with 99.9% of enantiometric excess (e.e.) was obtained. The established bioreduction reaction system could tolerate higher substrate concentrations of 3,5- bis(trifluoromethyl) acetophenone, and afforded a satisfactory yield and excellent product e.e. for the desired (R)-chiral alcohol, thus providing an alternative to the chemical synthesis of (R)-[3,5-bis(trifluoromethyl)phenyl] ethanol.

Authors+Show Affiliations

College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23462007

Citation

Ouyang, Qi, et al. "Efficient Enantioselective Synthesis of (R)-[3,5-bis(trifluoromethyl)phenyl] Ethanol By Leifsonia Xyli CCTCC M 2010241 Using Isopropanol as Co-substrate." Journal of Microbiology and Biotechnology, vol. 23, no. 3, 2013, pp. 343-50.
Ouyang Q, Wang P, Huang J, et al. Efficient enantioselective synthesis of (R)-[3,5-bis(trifluoromethyl)phenyl] ethanol by Leifsonia xyli CCTCC M 2010241 using isopropanol as co-substrate. J Microbiol Biotechnol. 2013;23(3):343-50.
Ouyang, Q., Wang, P., Huang, J., Cai, J., & He, J. (2013). Efficient enantioselective synthesis of (R)-[3,5-bis(trifluoromethyl)phenyl] ethanol by Leifsonia xyli CCTCC M 2010241 using isopropanol as co-substrate. Journal of Microbiology and Biotechnology, 23(3), pp. 343-50.
Ouyang Q, et al. Efficient Enantioselective Synthesis of (R)-[3,5-bis(trifluoromethyl)phenyl] Ethanol By Leifsonia Xyli CCTCC M 2010241 Using Isopropanol as Co-substrate. J Microbiol Biotechnol. 2013;23(3):343-50. PubMed PMID: 23462007.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Efficient enantioselective synthesis of (R)-[3,5-bis(trifluoromethyl)phenyl] ethanol by Leifsonia xyli CCTCC M 2010241 using isopropanol as co-substrate. AU - Ouyang,Qi, AU - Wang,Pu, AU - Huang,Jin, AU - Cai,Jinbo, AU - He,Junyao, PY - 2013/3/7/entrez PY - 2013/3/7/pubmed PY - 2013/8/27/medline SP - 343 EP - 50 JF - Journal of microbiology and biotechnology JO - J. Microbiol. Biotechnol. VL - 23 IS - 3 N2 - (R)-[3,5-Bis(trifluoromethyl)phenyl] ethanol is a key chiral intermediate for the synthesis of aprepitant. In this paper, an efficient synthetic process for (R)-[3,5- bis(trifluoromethyl)phenyl] ethanol was developed via the asymmetric reduction of 3,5-bis(trifluoromethyl) acetophenone, catalyzed by Leifsonia xyli CCTCC M 2010241 cells using isopropanol as the co-substrate for cofactor recycling. Firstly, the substrate and product solubility and cell membrane permeability of biocatalysts were evaluated with different co-substrate additions into the reaction system, in which isopropanol manifested as the best hydrogen donor of coupled NADH regeneration during the bioreduction of 3,5-bis(trifluoromethyl) acetophenone. Subsequently, the optimization of parameters for the bioreduction were undertaken to improve the effectiveness of the process. The determined efficient reaction system contained 200 mM of 3,5-bis(trifluoromethyl) acetophenone, 20% (v/v) of isopropanol, and 300 g/l of wet cells. The bioreduction was executed at 30°C and 200 rpm for 30 h, and 91.8% of product yield with 99.9% of enantiometric excess (e.e.) was obtained. The established bioreduction reaction system could tolerate higher substrate concentrations of 3,5- bis(trifluoromethyl) acetophenone, and afforded a satisfactory yield and excellent product e.e. for the desired (R)-chiral alcohol, thus providing an alternative to the chemical synthesis of (R)-[3,5-bis(trifluoromethyl)phenyl] ethanol. SN - 1738-8872 UR - https://www.unboundmedicine.com/medline/citation/23462007/Efficient_enantioselective_synthesis_of__R__[35_bis_trifluoromethyl_phenyl]_ethanol_by_Leifsonia_xyli_CCTCC_M_2010241_using_isopropanol_as_co_substrate_ L2 - http://www.jmb.or.kr/journal/viewJournal.html?doi=JMB023-03-09 DB - PRIME DP - Unbound Medicine ER -