Search

CN-121974845-A - Polyhydroxy pyridone compound and preparation method and application thereof

CN121974845ACN 121974845 ACN121974845 ACN 121974845ACN-121974845-A

Abstract

The application relates to the technical field of compounds, and particularly discloses a polyhydroxy pyridone compound, a preparation method and application thereof. According to the preparation method, the fermentation liquor is heated and then subjected to solid-liquid separation to remove denatured proteins and other insoluble substances in the fermentation liquor, filtrate is obtained and then is heated, evaporated and concentrated, then poor solvent is added, the temperature is reduced, the stirring is carried out uniformly, crystallization is thorough, the filtration is carried out, crude crystals are washed in a suspending manner by using aqueous solution of the poor solvent, and then the crude crystals are dried, so that the polyhydroxy pyridone compound with the purity of more than 95% and the yield of more than 95% can be obtained by adopting the preparation method.

Inventors

  • Request for anonymity
  • Request for anonymity
  • Request for anonymity

Assignees

  • 南京合谷生命生物科技有限公司

Dates

Publication Date
20260505
Application Date
20251209

Claims (10)

  1. 1. The polyhydroxy pyridone compound is characterized in that the structural formula of the polyhydroxy pyridone compound is shown as a formula (I); Formula (I).
  2. 2. The method for preparing polyhydroxy pyridone compounds of claim 1, comprising the steps of: 1) Fermenting engineering bacteria IN10-06 to obtain fermentation liquor, heating the fermentation liquor, and performing solid-liquid separation to obtain filtrate; 2) Heating, evaporating and concentrating the filtrate to obtain a concentrated solution, adding a poor solvent into the concentrated solution, cooling, crystallizing and stirring, filtering after crystallization is complete, suspending and washing crude crystals by using an aqueous solution containing the poor solvent, and drying to obtain polyhydroxy pyridone compounds; Wherein the preservation number of the engineering bacteria IN10-06 is CCTCCNO: M2024514, and the engineering bacteria IN10-06 is preserved IN China center for type culture Collection.
  3. 3. The method for preparing polyhydroxy pyridone compounds according to claim 2, wherein in step 1), the method for preparing the fermentation broth comprises the following steps: a. inoculating engineering bacteria IN10-06 into a culture medium, and adding kanamycin for culturing to obtain seed liquid; b. Inoculating and transferring the seed liquid into a basic fermentation culture medium containing an inducer for double-stage fermentation, controlling residual sugar to be less than 5g/L in the fermentation process, and ending the fermentation after the pH value is rebounded to 7.2-7.5 or the dissolved oxygen is rebounded to 70-80%, so as to obtain fermentation liquid; Wherein, the double-stage fermentation comprises a first-stage fermentation and a second-stage fermentation; The first stage fermentation comprises the following conditions: The culture temperature before induction is 30-37 ℃, the OD 600 is more than or equal to 50 and is reduced to 20-25 ℃, the initial rotating speed is 300-500 rpm, the dissolved oxygen amount is 30-35%, the ventilation ratio is 0.8-1.5 vvm, and the pH is 6.9-7.0; the second stage fermentation comprises the following conditions: the temperature is 20-25 ℃, the rotating speed is 800-1000 rpm, the ventilation ratio is 1.2-1.5 vvm, and the pH is 6.9-7.0.
  4. 4. A process for the preparation of polyhydroxy pyridones according to claim 3, wherein the basal fermentation medium comprises the following concentrations of components: 5-10 g/L of yeast powder, 20-40 g/L of 10% liquid glucose, 10-20 g/L of ammonium sulfate, 0.2-1 g/L of monopotassium phosphate, 0.2-0.4 g/L of magnesium sulfate heptahydrate, 0.01-0.02 g/L of manganese sulfate monohydrate, 2-4 mu g/L of biotin, 0.2-0.4 mg/L of VB 1 , 1-2 g/L of sodium glutamate, water as a solvent and pH=7.0-7.5.
  5. 5. The method of claim 3, wherein the fermenting further comprises feeding with a feeding medium, and restarting feeding when residual sugar is >15g/L, and residual sugar is <5 g/L; The feed medium comprises the following components in concentration: 400-600 g/L of glucose, 2-4 g/L of magnesium sulfate heptahydrate, 40-80 g/L of ammonium chloride, water as a solvent, and pH=7.0-7.5.
  6. 6. The method for preparing polyhydroxy pyridone compounds according to claim 2, wherein in step 1), the heating temperature is 60 to 80 ℃ and the holding time is 1 to 2 hours; And/or, in the step 1), the heating evaporation concentration multiple is 20-50X.
  7. 7. The method for preparing polyhydroxy pyridone compounds of claim 2, wherein in step 2), the poor solvent comprises one of methanol, ethanol, isopropanol and acetonitrile; Preferably, the poor solvent is isopropanol.
  8. 8. The method for preparing polyhydroxy pyridone compounds according to claim 2, wherein the temperature of the cooling crystallization in step 2) is 2-12 ℃, and the stirring time is 1-3 hours.
  9. 9. The method for producing a polyhydroxypyridone compound according to claim 2, wherein the mass ratio of the poor solvent to water in the aqueous solution containing the poor solvent in the step 2) is (1 to 5): 1; And/or the feeding mass ratio of the crude crystal to the aqueous solution containing the poor solvent is 1 (10-30).
  10. 10. Use of polyhydroxy pyridone compounds as claimed in claim 1 in dyes.

Description

Polyhydroxy pyridone compound and preparation method and application thereof Technical Field The application relates to the technical field of compounds, in particular to a polyhydroxy pyridone compound, a preparation method and application thereof. Background Pyridone compounds are a class of heterocyclic molecules with a wide range of biological activities, and play an important role in pharmaceutical chemistry and natural product chemistry. Studies have shown that the compounds generally show pharmacological activities such as antibacterial, anti-inflammatory and antitumor activities. For example, 5-hydroxy-2-pyridone derivatives have been shown to have a remarkable inhibitory effect on methicillin-resistant staphylococcus aureus (MRSA), 3, 4-dihydroxypyridone compounds exhibit good antioxidant properties, 2-pyridone compounds are used for the synthesis of antibacterial agents (e.g., quinolones), antiviral agents or antitumor agents, 4-pyridone compounds are combined with metal ions such as iron, aluminum and the like for the treatment of iron overload diseases, such as the effect similar to deferoxamine, and 6-amino-2-pyridone compounds can be used as dye intermediates for the synthesis of azo dyes. Pyridone compounds generally show pharmacological activities such as antibacterial, anti-inflammatory and anti-tumor activities, and can be used for synthesizing bioactive substances from precursor substances, and used as raw materials or intermediates for developing and preparing novel antibiotics, medicines and dyes. The polyhydroxy aminopyridone is further separated and purified from the blue-looking fermentation liquor, and the compound can be applied to dyeing to a certain extent. Therefore, the recycling of the blue-looking fermentation liquor can be realized, the environmental protection problem can be solved, and the process economy is enhanced. Disclosure of Invention The application aims to overcome the defects of the prior art and provide a polyhydroxy pyridone compound, a preparation method and application thereof. The polyhydroxy pyridone compound is separated from the blue-viewing fermentation liquid, can be used for synthesizing bioactive substances from precursor substances, and can be used as a raw material or an intermediate for developing and preparing novel antibiotics, medicines and dyes. In order to achieve the above purpose, the technical scheme adopted by the application is as follows: The application provides a polyhydroxy pyridone compound, the structural formula of which is shown as a formula (I), and the polyhydroxy pyridone compound is named as 5-amino-1, 3, 4-trihydroxy-1, 2,3, 6-tetrahydropyridine-2, 6-dione. Formula (I). The application provides a polyhydroxy pyridone compound which can be used for synthesizing bioactive substances from precursor substances and used as a raw material or an intermediate for developing and preparing novel antibiotics, medicines and dyes. The application also provides a preparation method of the polyhydroxy pyridone compound, which comprises the following steps: 1) Fermenting engineering bacteria IN10-06 to obtain fermentation liquor, heating the fermentation liquor, and performing solid-liquid separation to obtain filtrate; 2) Heating, evaporating and concentrating the filtrate to obtain a concentrated solution, adding a poor solvent into the concentrated solution, cooling, crystallizing and stirring, filtering after crystallization is complete, suspending and washing crude crystals by using an aqueous solution containing the poor solvent, and drying to obtain polyhydroxy pyridone compounds; Wherein the preservation number of the engineering bacteria IN10-06 is CCTCCNO: M2024514, and the engineering bacteria IN10-06 is preserved IN China center for type culture Collection. The polyhydroxy pyridone compound is obtained by separating and purifying the strain fermentation broth with the preservation number, purifying the strain fermentation broth by utilizing the difference of solubility of substances through conditions of different solvents and the like, heating the fermentation broth, then carrying out solid-liquid separation to remove denatured proteins and other insoluble matters in the fermentation broth, obtaining filtrate, heating, evaporating, concentrating, adding a poor solvent, cooling, uniformly stirring, crystallizing thoroughly, filtering, suspending, washing a crude product crystal by using an aqueous solution of the poor solvent, and drying. The application separates a polyhydroxy pyridone compound from fermentation broth, and can be used for synthesizing bioactive substances from precursor substances. As a preferred embodiment of the preparation method of polyhydroxy pyridone compounds, in the step 1), the preparation method of the fermentation broth specifically comprises the following steps: a. inoculating engineering bacteria IN10-06 into a culture medium, and adding kanamycin for culturing to obtain seed liquid; b. Inoculating