Synthesis method of chiral 1, 3-dihydroxy-1-aryl acetone compound

A technology of aryl acetone and hydroxypyruvate, applied in the field of biocatalysis, can solve the problems of low activity and narrow transketolase

Active Publication Date: 2021-05-28
TIANJIN INST OF IND BIOTECH CHINESE ACADEMY OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the substrate spectrum of transketolase is still relatively narrow, and the low activity is also the main factor limiting its development and application.
At present, there is no research report on the synthesis of dihydroxyketones from hydroxypyruvate catalyzed by pyruvate decarboxylase

Method used

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  • Synthesis method of chiral 1, 3-dihydroxy-1-aryl acetone compound
  • Synthesis method of chiral 1, 3-dihydroxy-1-aryl acetone compound
  • Synthesis method of chiral 1, 3-dihydroxy-1-aryl acetone compound

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0022] Example 1: Construction and culture of genetically engineered bacteria

[0023]The specific construction and cultivation method of the genetically engineered bacteria producing pyruvate decarboxylase is as follows: synthesizing the pyruvate decarboxylase nucleic acid sequence SEQ ID NO: 3 derived from Macrococcushajekii, constructing it into a pET series vector, in the host bacteria Escherichia coli Heterologous expression was performed. Thaw the strains stored at -80°C, streak the plates, and place them in a constant temperature incubator at 37°C for overnight culture. Select a single colony on the plate and inoculate it into 20 mL of LB medium containing the corresponding antibiotics, cultivate it for about 12 hours as the seed solution, and inoculate it into 700 mL of the LB medium containing the corresponding antibiotics according to the inoculum of 1%. Cultivated to OD 600 =0.6-0.8, IPTG with a final concentration of 0.1 mmol / L was added for induction at 25°C for...

Embodiment 2

[0025] Example 2: Pyruvate decarboxylase catalyzes the preparation of 1,3-dihydroxy-1-phenylacetone from benzaldehyde and hydroxypyruvate.

[0026] (1) Add 0.26g hydroxypyruvate (25mM), 0.01g ThDP (0.1mM), 3.00g pyruvate decarboxylase genetically engineered bacteria, 20mM benzaldehyde (dissolved in 20% DMSO) into 80mL water, and adjust the pH of the reaction system to 8.0, react at 25°C for 24h. After the reaction, the protein was removed by centrifugation, the supernatant was extracted with ethyl acetate, and the extraction was complete by thin-layer chromatography. The organic solvent is removed by rotary evaporation to obtain the crude product, the substrate conversion rate and product yield are detected by gas phase, and the ratio of product and by-product isomers is detected by liquid phase HPLC. The detection result is: pyruvate decarboxylase catalyzes the R configuration product, the ee value is >99%, the conversion rate of benzaldehyde substrate is 61%, and the ratio ...

Embodiment 3

[0032] Example 3: Pyruvate decarboxylase and D-amino acid oxidase genetically engineered bacteria to prepare 1,3-dihydroxy-1-arylacetone.

[0033] 2.00g D-amino acid oxidase genetically engineered bacteria, 3.00g pyruvate decarboxylase genetically engineered bacteria, 1.05g D-Serine (100mM), 0.02g MgCl 2 ·6H 2 O (1mM), 0.01g ThDP (0.1mM), 60mg catalase (15KU) were added to 80mL water, the pH of the reaction system was adjusted to 7.0, incubated at 25°C, 200rpm for 1h, then added 20mM benzaldehyde (dissolved in 20% DMSO) and reacted for 24h . After the reaction, the protein was removed by centrifugation, the supernatant was extracted with ethyl acetate, and the extraction was complete by thin-layer chromatography. The organic solvent is removed by rotary evaporation to obtain the crude product, the substrate conversion rate and product yield are detected by gas phase, and the ratio of product and by-product isomers is detected by liquid phase HPLC. The detection results are:...

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Abstract

The invention discloses a method for generating optically pure chiral 1, 3-dihydroxy-1-substituted aryl acetone by catalyzing hydroxypyruvic acid to react with benzaldehyde with different substituent groups through a biocatalyst. In order to obtain the hydroxypyruvic acid at a low cost, the hydroxypyruvic acid is obtained by converting D-serine with D-amino acid oxidase without separation, and the method has the remarkable characteristics of mild reaction conditions, good stereoselectivity, no pollution and the like.

Description

technical field [0001] The invention belongs to the field of biocatalysis, and relates to using a biocatalyst pyruvate decarboxylase to catalyze the reaction of hydroxypyruvate and benzaldehyde with different substituents to generate optically homochiral 1,3-dihydroxy-1-arylacetone compounds. Background technique [0002] 1,3-Dihydroxy ketone compounds are important intermediates for the synthesis of many substances. Using hydroxy ketone compounds, chiral amino alcohols, rare sugars and steroids can be obtained. They are used in functional food, medicine, medicine and synthetic chemistry. Has huge application potential. [0003] At present, the methods for synthesizing 1,3-dihydroxy-1-arylacetone are mainly divided into two categories-chemical method and enzymatic method. According to literature reports, Mark E.B.Smith et al. used 3-(4-morpholinyl)-propanesulfonic acid as a solvent to promote the formation of C-C bonds between acceptor aldehydes and donor aldehydes to achie...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12N9/88C12P7/26
CPCC12N9/88C12P7/26C12Y401/01001
Inventor 姚培圆李宇崔云凤陈曦冯进辉吴洽庆朱敦明马延和
Owner TIANJIN INST OF IND BIOTECH CHINESE ACADEMY OF SCI
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