Trichoderma asperellum and application thereof in synthesizing (R)-[3,5-dual (trifluoromethyl) phenyl] ethanol

A technology of Trichoderma aculeatus and trifluoromethyl, which is applied in the field of biocatalysis and can solve the problems that are not suitable for industrial applications

Inactive Publication Date: 2010-06-09
ZHEJIANG UNIV OF TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Because this strain can only obtain higher yields when the substrate

Method used

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  • Trichoderma asperellum and application thereof in synthesizing (R)-[3,5-dual (trifluoromethyl) phenyl] ethanol
  • Trichoderma asperellum and application thereof in synthesizing (R)-[3,5-dual (trifluoromethyl) phenyl] ethanol
  • Trichoderma asperellum and application thereof in synthesizing (R)-[3,5-dual (trifluoromethyl) phenyl] ethanol

Examples

Experimental program
Comparison scheme
Effect test

Example Embodiment

[0057] Example 1: Obtaining wet mycelium

[0058] The seed medium formula is as follows: glucose 25g / L, peptone 27.5g / L, (NH 4 ) 2 SO 4 3g / L, KH 2 PO 4 1g / L, MgSO 4 1.25g / L, ZnSO 4 ·7H 2 O 0.008g / L, prepared with distilled water, pH 6.0.

[0059] The formula of the fermentation medium is the same as that of the seed medium, which is prepared with tap water;

[0060] Insert the mature slant strain into a 250mL shake flask containing 70mL seed culture medium, cultivate at 30°C and 200r / min for 19 hours, and then transfer the seed solution to a 70mL fermentation at an inoculum volume ratio of 5% Culture medium in a 250mL shake flask at 30°C and 200r / min for 21 hours. After the cultivation, the fermentation broth was centrifuged and washed with phosphate buffer, and the wet mycelium was collected for use.

Example Embodiment

[0061] Example 2: Detection method of product concentration

[0062] After the completion of the biotransformation reaction, the reaction solution was extracted with an equal volume of ethyl acetate (10 mL), and the concentration of the product and unreacted substrate in the 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. The specific operating conditions of gas chromatography are: injector temperature 250℃, detector temperature 250℃, column temperature 80℃, hold for 2min, raise temperature at 4℃ / min to 180℃ for 10min, carrier gas is nitrogen, flow rate is 1.5mL / min , The split ratio is 1:20, and the injection volume is 1μL. According to the spectrum obtained by gas chromatography, the relative correction factor method is used to calculate the concentration of the product in the reaction solution, and then the yield (Yield) and the ee value of the pr...

Example Embodiment

[0063] Example 3:

[0064] The wet mycelium obtained in Example 1 was suspended in 10 mL of phosphate buffer (pH 5.7). The concentration of the wet mycelium by dry weight was 35 g / L; 10 mmol / L of [3,5-bis( Trifluoromethyl)phenyl]ethanone was used as a substrate, and 50g / L glucose was added as an auxiliary substrate, and the reaction was placed in a shaker at 30°C and 200r / min for 10 hours. Using the detection method of Example 2, the concentration of the product (R)-[3,5-bis(trifluoromethyl)phenyl]ethanol is 4.2 mmol / L, the optical purity ee value is 94.7%, and the yield is 42.2% (thorn The gas chromatogram of the bioreduction reaction extract of Trichoderma ZJPH0810 strain is shown figure 2 ).

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Abstract

The invention provides a new strain-Trichoderma asperellum ZJPH0810, and an application thereof in microbial catalysis asymmetric synthesis of (R)-[3,5-dual (trifluoromethyl) phenyl] ethanol. The Trichoderma asperellum ZJPH0810 is preserved in the CCTCC, the address is Wuhan University, Wuhan Province, China, 430072 with the preservation date of 16th, December, 2009 and the preservation number of CCTCC No: M209307. The strain of the invention is used for the microbial asymmetric reduction of 1-[3,5-dual (trifluoromethyl) phenyl] ethanol to prepare the (R)-[3,5-dual (trifluoromethyl) phenyl] ethanol which has the advantages of high stereoselectivity, high optical purity and the like. When substrate concentration reaches 80 mmol/ L, yield can reach 53.4%. The invention screens and obtains new microbe strains different from the existing similar research reports, and can obtain the yield of (R)-[3,5-dual (trifluoromethyl) phenyl] ethanol product, which is higher than the yield reported by the document under the same substrate concentration, so that the invention provides a beneficial reference on the aspect of preparing the key chiral intermediates of Emend drugs with a microbiological method.

Description

(1) Technical field [0001] The invention belongs to the technical field of biocatalysis, and relates to a new strain-Trichoderma asperellum (Trichoderma asperellum) ZJPH0810, and its catalytic asymmetric synthesis of (R)-[3,5-bis(trifluoromethyl) ) Phenyl] ethanol application. (2) Background technology [0002] Chiral alcohols containing aromatic groups are key chiral intermediates for the synthesis of many chiral drugs. Aprepitant, trade name: Emend , Chemical name: 5-[[(2R,3S)-2-[(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy]-3-(4-fluorobenzene Yl)-4-morpholinyl-]methyl]-1,2-dihydro-3H-1,2,4-triazol-3-onyl. In 2003, the US Food and Drug Administration (FDA) approved aprepitant as a drug for nausea and vomiting caused by highly emetic chemotherapy regimens. It is a novel antiemetic drug-NK-1 receptor antagonist. NK-1 receptor antagonist has a wide range of antiemetic effects on various emetic stimuli, and has a prominent role in delayed emesis. Aprepitant is currently the o...

Claims

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Application Information

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IPC IPC(8): C12N1/14C12P7/22C12R1/885
Inventor 王普何军邀唐俊
Owner ZHEJIANG UNIV OF TECH
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