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A kind of preparation method and application of indole-3-carboxaldehyde

A formaldehyde and indole technology, applied in the field of medicine, can solve the problems of difficult separation of reactants and products, non-unique products, harsh experimental conditions, etc., and achieve huge development potential and application prospects, strong xanthine oxidase inhibitory activity, low cost cheap effect

Active Publication Date: 2021-05-18
HAIKOU EXPERIMENTAL STATION CHINESE ACAD OF TROPICAL AGRI SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In 1945, the Blume group produced indole-3 carboxaldehyde through the Reimer-Tiemann reaction with a yield of 52%, but the reaction selectivity was poor and the product was not unique (Blume R C, Lindwall H G. J. Org. Chem., 1945, 10:255 )
In 1994, Macor etc. used acid chloride and Grignard reagent to synthesize 3-formylindole, but Grignard reagent is a strong nucleophile, which is easy to react with acid chloride, which also causes the low yield of this reaction method (45 %) (Macor J E, Blank D H, Fox C B, et al. J. Med. Chem., 1994, 37:2509)
In 2010, Taylor et al. improved the Friedel-Crafts acylation method for the synthesis of 3-acylindole. Unlike the traditional Friedel-Crafts acylation reaction, the catalyst used in the improved reaction was DBN, so that the yield could reach 57%-100%, which solves the harsh conditions that require strict anhydrous in the traditional process, but the catalyst is expensive, the reactants and products are difficult to separate, the experimental conditions are harsh, and the yield is low, which limits its industrial application (Taylor J E, Matthew D J, Jonathan M. J. Org. Lett., 2010, 12:5740201)

Method used

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  • A kind of preparation method and application of indole-3-carboxaldehyde
  • A kind of preparation method and application of indole-3-carboxaldehyde
  • A kind of preparation method and application of indole-3-carboxaldehyde

Examples

Experimental program
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Effect test

Embodiment 1

[0033] Preparation of indole-3-carbaldehyde

[0034]1. Cultivation and fermentation of Vibrio New Caledonia

[0035] A single colony of Vibrio New Caledonia CGJ02-2 (deposited in China Center for Type Culture Collection (CCTCC) on December 18, 2017, deposit number: CCTCC M 2017802) was inoculated with an inoculation loop from a 2216E solid plate to Six 250 ml Erlenmeyer flasks each containing 100 ml of LB liquid medium containing 2% NaCl (g / ml) were cultured overnight at 28°C to 30°C and 160 rpm. The activated bacterial liquid was expanded and cultured with LB medium containing 2% NaCl at a ratio of 1:50, with a total volume of 16L, at 28°C-30°C, 120rpm for 10-12 days. The fermented liquid was centrifuged at 8000 rpm for 10 minutes in a high-speed centrifuge to remove the bacteria and harvest the supernatant.

[0036] 2. Extraction of fermentation broth

[0037] The culture supernatant was submerged in an equal volume of ethyl acetate for 24 hours, while shaking continuousl...

Embodiment 2

[0044] Determination of the Structure of Indole-3-Carboxaldehyde

[0045] Take part F6.2.2.1 obtained in Example 1, and use 2D-NMR (nuclear magnetic resonance technique) (BRUKER AVANCE 500 MHz) for structure identification. in, figure 1 is the H-NMR spectrum, figure 2 for 13 C-NMR spectrum, image 3 is the COZY map, Figure 4 is the HMBC spectrum, Figure 5 It is the HSQC chart. Through structural analysis, the compound prepared by the present invention is indole-3-carboxaldehyde, and its chemical structural formula is:

[0046]

Embodiment 3

[0048] Determination of the inhibitory activity of indole-3-carbaldehyde on Xantine oxidase (XO)

[0049] Add 120 μL of 0.02 mol / L PBS (pH 7.4), 20 μL of different concentrations of indole-3-carbaldehyde, 40 μL of 1.5 mmol / L xanthine, and 20 μL of 0.5 U / mL xanthine oxidase in a 96-well plate , mixed thoroughly, and measured the absorbance at a wavelength of 295 nm with a full-wavelength microplate reader, using allopurinol as a positive control, and repeated 3 times to obtain the average value. Enzyme activity experiment is set as experimental group, experimental blank group, negative control, negative blank control, positive control and positive blank control 6 groups.

[0050] Experimental blank group: 40µl xanthine + 20µl sample + 120µl PBS + 20µl PBS

[0051] Negative control: 40µl xanthine + 20µl PBS + 120µl PBS + 20µl enzyme

[0052] Negative blank control: 40µl xanthine + 20µl PBS + 120µl PBS + 20µl PBS

[0053] Positive control: 40µl xanthine + 20µl allopurinol + 12...

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Abstract

The invention provides a method for preparing indole-3-formaldehyde, comprising the following steps: (1) inoculating Vibrio New Caledonia CGJ02-2 into LB liquid medium for cultivation, and centrifuging to remove bacteria after the cultivation body, harvest the fermentation supernatant; (2) extract the fermentation supernatant with an organic solvent, concentrate the organic phase under reduced pressure to obtain a crude extract; (3) separate the indole-3-formaldehyde from the obtained crude extract . In the present invention, the indole-3-formaldehyde is produced by a microbial fermentation method, and a large amount of indole-3-formaldehyde can be obtained only by cultivating the microorganisms with a simple culture medium. The method of the invention is not only low in cost, but also environmentally friendly than chemical synthesis. The in vitro enzyme activity test of indole-3-formaldehyde shows that it has strong xanthine oxidase inhibitory activity, and has great development potential and application prospects in the treatment of hyperuricemia and gout.

Description

technical field [0001] The present invention relates to the technical field of medicine, in particular to a method for preparing indole-3-carboxaldehyde by microbial fermentation and the application of indole-3-carboxaldehyde in the preparation of medicines for treating hyperuricemia and gout . Background technique [0002] Uric acid is a product of purine metabolism in the human body. Due to the limited solubility of uric acid in body fluids, when purine metabolism in the body is disordered or excessive intake of purines leads to excessive purine content in the body, excessive uric acid is produced / or uric acid excretion is reduced, and the concentration of uric acid accumulated in body fluids When its saturation concentration is exceeded, crystals are easily precipitated in tissues, causing hyperuricemia, and about 5% to 12% of patients with hyperuricemia eventually develop into gout (gout). Gout has become the second most common metabolic disease after diabetes. Therefo...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C12P17/10C07D209/12A61P19/06C12R1/63
CPCA61P19/06C07D209/12C12P17/10
Inventor 谭琳谭凯伊莎贝尔范梦凯孙香荣
Owner HAIKOU EXPERIMENTAL STATION CHINESE ACAD OF TROPICAL AGRI SCI
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