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Leifsonia xyli and use thereof in preparation of (R)-[3,5-bis(trifluoromethyl)phenyl]ethanol

The technology of Reversonella and trifluoromethyl is applied to Reversonella and the application field of preparing (R)-[3,5-bis(trifluoromethyl)phenyl]ethanol, which can Solve problems such as unsuitable for industrial application and low substrate concentration

Active Publication Date: 2011-06-22
特康药业集团有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Because the substrate concentration of the catalyzed reaction of this strain is low, it is not suitable for industrial application

Method used

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  • Leifsonia xyli and use thereof in preparation of (R)-[3,5-bis(trifluoromethyl)phenyl]ethanol
  • Leifsonia xyli and use thereof in preparation of (R)-[3,5-bis(trifluoromethyl)phenyl]ethanol
  • Leifsonia xyli and use thereof in preparation of (R)-[3,5-bis(trifluoromethyl)phenyl]ethanol

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0051] Embodiment 1: the detection method of product

[0052] The optical purity and yield of the target product were determined by GC: the concentration of the product and residual substrate in the reaction extract was analyzed by gas chromatography and quantified by the internal standard method. The internal standard is dodecane. Take 1mL extract and add 2μL dodecane for analysis. Gas chromatography conditions: Japan Shimadzu GC-2014 gas chromatograph, Zhejiang University N2000 chromatography workstation; American Varian CP-Chirasil-Dex chiral capillary gas chromatography column (25m×0.25mm×0.25μm). The carrier gas is high-purity nitrogen, the flow rate is 2mL / min; the injection volume is 1 μL, and the split ratio is 15:1; the temperature of the detector and the injection port are both 250°C; the temperature of the chromatographic column is 80-180°C; the heating rate: 4°C / min; the detector is FID.

[0053] The concentrations of substrate and product in the reaction solut...

Embodiment 2

[0059] Embodiment 2: the acquisition of wet fungus cells

[0060] Seed medium formula: glucose 10g / L, peptone 5g / L, yeast extract 4g / L, (NH 4 ) 2 SO 4 2g / L, KH 2 PO 4 1g / L, NaCl 0.5g / L, MgSO 4 ·7H 2 O 0.5g / L, solvent is water, pH 6.5.

[0061] Fermentation medium formula: glucose 25g / L, yeast extract 20g / L, KH 2 PO 4 4g / L, NaCl 0.4g / L, MgSO 4 ·7H 2 O 0.6g / L, Li 2 SO 4 0.2g / L, the solvent is water, pH 6.5.

[0062] Pick a ring of bacteria (CCTCC NO: M 2010241) from the mature slant and insert it into a 250mL shake flask with 200mL seed medium, cultivate it at 30°C and 200rpm for 24 hours to obtain a seed solution, and then inoculate it with a volume ratio of 8% Transfer the seed solution to a 250mL shake flask containing 100mL of fermentation medium, and culture at 30°C and 200rpm for 48 hours. After the cultivation, the fermentation broth was centrifuged and washed once with phosphate buffer, and the wet bacterial cells were collected for future use.

Embodiment 3

[0064] The wet thalline obtained in Example 2 is suspended in 10 mL of phosphate buffer (pH 8.0), and the wet thalline concentration is 50 g / L by wet weight; add 20 mmol / L of [3,5-bis(trifluoro Methyl)phenyl]ethanone was used as a substrate, and 50g / L of glucose was added as an auxiliary substrate, and placed in a shaker at 30°C and 200r / min for 12h. Using the detection method of Example 1, the concentration of the product (R)-[3,5-di(trifluoromethyl)phenyl]ethanol was 6.2mmol / L, the optical purity ee value was 99.4%, and the yield was 31.1%.

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Abstract

The invention provides Leifsonia xyli which is a new strain that can be used in the preparation of high-optical purity (R)-[3,5-bis(trifluoromethyl)phenyl]ethanol by asymmetric reduction of [3,5-bis(trifluoromethyl)phenyl]ethanone in presence of a microbe catalyst, and use thereof. The Leifsonia xyli HS0904 was collected in China Center for Type Culture Collection located in Wuhan University (postcode:430072) in Wuhan, China on September 21, 2010, with a collection number CCTCC No.M2010241. The use of the new strain in the catalytic preparation of the optically pure (R)-[3,5-bis(trifluoromethyl)phenyl]ethanol has the advantages of high substrate concentration, high stereoselectivity, high optical purity of product and the like. The strain is different from microbes reported in researches of the same kind, for the concentration of the substrate to be converted catalytically and the yield are both higher than those reported in documents. Thus, a beneficial reference is provided for the research on the preparation of (R)-[3,5-bis(trifluoromethyl)phenyl]ethanol which is a key chiral intermediate of an Aprepitant medicine by a microbial catalysis process.

Description

(1) Technical field [0001] The present invention relates to a strain that can be used for microbial catalytic asymmetric reduction of [3,5-bis(trifluoromethyl)phenyl]ethanone to prepare high optical purity (R)-[3,5-bis(trifluoromethyl)benzene A new strain of ethanol—Leifsonia xyli HS0904 and its application. (2) Background technology [0002] The chemical structural formula of (R)-[3,5-bis(trifluoromethyl)phenyl]ethanol is: [0003] [0004] (R)-[3,5-bis(trifluoromethyl)phenyl]ethanol is a synthetic drug Aprepitant (trade name: ) is an important chiral intermediate. Aprepitant chemical name: 5-[[(2R,3S)-2-[(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy]-3-( 4-fluorophenyl)-4-morpholinyl-]methyl]-1,2-dihydro-3H-1,2,4-triazol-3-onyl. In 2003, the U.S. Food and Drug Administration (FDA) approved aprepitant for nausea and vomiting caused by highly emetogenic chemotherapy regimens. It is an antiemetic drug with a new mechanism-NK-1 receptor antagonist. NK-1 receptor antag...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12N1/20C12P41/00C12P7/22C12R1/01
Inventor 王普何军邀蔡进波欧阳启
Owner 特康药业集团有限公司
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