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CN-121991043-A - Flavonol derivative containing 1,2,3, 4-tetrahydroquinoline and preparation method and application thereof

CN121991043ACN 121991043 ACN121991043 ACN 121991043ACN-121991043-A

Abstract

The invention discloses a flavonol derivative containing 1,2,3, 4-tetrahydroquinoline, and a preparation method and application thereof, and belongs to the technical field of pesticide synthesis. According to the invention, 1,2,3, 4-tetrahydroquinoline with excellent activity is introduced into a flavonol structure, a series of flavonol derivatives containing 1,2,3, 4-tetrahydroquinoline are synthesized, and the flavonol derivatives containing 1,2,3, 4-tetrahydroquinoline synthesized by the invention can effectively inhibit plant pathogenic bacteria, especially phytophthora capsici and mango bacterial black spot bacteria through the activity test of inhibiting plant pathogenic bacteria of the flavonol derivatives containing 1,2,3, 4-tetrahydroquinoline.

Inventors

  • XUE WEI
  • ZHANG HONGYU
  • HU QINGXUE
  • WANG QING
  • GENG XIAOTING
  • YANG HAN
  • SHEN DAN
  • XIN LANG
  • YANG YING
  • HAO GEFEI

Assignees

  • 贵州大学
  • 黔南州烟草公司平塘县分公司

Dates

Publication Date
20260508
Application Date
20260203

Claims (10)

  1. 1. A flavonol derivative containing 1,2,3, 4-tetrahydroquinoline, which is characterized by having the following structural formula: ; Wherein R is independently selected from H, one or more halogens, one or more alkyl groups, and one or more alkoxy groups.
  2. 2. The flavonol derivative containing 1,2,3, 4-tetrahydroquinoline according to claim 1, wherein the alkyl group comprises-CH 3 , -CH 2 CH 3 , -CH(CH3) 2 , -C(CH 3 ) 3 and the halogen comprises-F, -Cl, -Br.
  3. 3. A process for the preparation of a flavonol derivative comprising 1,2,3, 4-tetrahydroquinoline as claimed in claim 1 or 2, characterised in that the process comprises the steps of: (1) 1,2,3, 4-tetrahydroquinoline and chloroacetyl chloride are taken as raw materials, sodium acetate is taken as a catalyst, stirring is carried out at normal temperature overnight, ethyl acetate is used for extraction after the reaction is finished, and an intermediate a is obtained through reduced pressure distillation; the structural formula of the intermediate a is as follows: ; (2) Taking o-hydroxyacetophenone, substituted benzaldehyde as a raw material and sodium hydroxide as a catalyst, stirring at normal temperature, pouring the reaction system into ice water after the reaction is finished, regulating the pH to 5-6, standing, and carrying out suction filtration to obtain an intermediate b; The structural formula of the intermediate b is ; (3) Taking the intermediate b as a raw material, taking sodium hydroxide as a catalyst, taking hydrogen peroxide as an oxidant, taking methanol as a solvent, stirring at normal temperature, pouring ice water after the reaction is finished, standing and filtering to obtain an intermediate c; the structural formula of the intermediate c is as follows: ; (4) Taking the intermediate c and 1, 3-dibromopropane as raw materials, potassium carbonate as a catalyst, acetonitrile as a solvent, heating and refluxing, and reacting to obtain an intermediate d; The structural formula of the intermediate d is as follows: ; taking the intermediate d and piperazine as raw materials, potassium carbonate as a catalyst, acetonitrile as a solvent, heating and refluxing, and reacting to obtain an intermediate e; The structural formula of the intermediate e is as follows: ; (6) Taking the intermediate a and the intermediate e as raw materials, taking potassium carbonate as a catalyst, taking acetonitrile as a solvent, heating and refluxing, finishing the reaction, extracting with dichloromethane, removing an extractant by reduced pressure distillation, and obtaining the flavonol derivative containing 1,2,3, 4-tetrahydroquinoline by column chromatography.
  4. 4. The preparation method of claim 2, wherein in the step (1), the molar ratio of 1,2,3, 4-tetrahydroquinoline to chloroacetyl chloride is 15.0:19.5, the reaction time at normal temperature is 12-15 h, the alkaline condition is provided by sodium acetate, the extractant is ethyl acetate, the molar ratio of o-hydroxyacetophenone to substituted benzaldehyde in the step (2) is 11.0:13.2, the reaction time is 40-48h, and the reagent for adjusting pH is 10% hydrochloric acid.
  5. 5. The process according to claim 3, wherein the molar ratio of the intermediate b to sodium hydroxide in step (3) is 13.4:40.1, the reaction time is 30-35h, and the pH-adjusting agent is 10% hydrochloric acid.
  6. 6. The preparation method of claim 3, wherein the molar ratio of the intermediate C to the 1, 3-dibromopropane to the potassium carbonate in the step (4) is 2.1:6.3:6.3, the rapid heating reflux step is that the intermediate C and the potassium carbonate react for 0.5h, then the 1, 3-dibromopropane is slowly added, the temperature is 80 ℃ and the reaction is heated for 8-10h, the separation step after the reaction is finished is that the reaction system is poured into water, dichloromethane is added for extraction, and the extract is evaporated to dryness, so that the intermediate d is obtained.
  7. 7. The preparation method of claim 3, wherein the molar ratio of the intermediate d to the piperazine to the potassium carbonate in the step (5) is 5.6:16.7:16.7, the rapid heating reflux step is that the piperazine and the potassium carbonate react for 0.5h, then the intermediate d is slowly added, the reaction time is 5-6h, and the preparation method further comprises a separation step, namely pouring the reaction system into purified water, adding dichloromethane for extraction, and evaporating the extract to dryness to obtain an intermediate e.
  8. 8. The preparation method of claim 3, wherein in the step (6), the molar ratio of the intermediate a to the intermediate e to the potassium carbonate is 4.1:6.2:12.4, the rapid heating reflux step is that the intermediate e and the potassium carbonate react for 0.5h, then the intermediate a is slowly added, the reaction is carried out for 5-6h at 80 ℃, the reaction is finished, the method further comprises a separation step of introducing the reaction system into purified water, adding dichloromethane for extraction, evaporating an extract liquid, and separating by column chromatography to obtain a target product, wherein the dichloromethane is methanol=30:1 (v/v).
  9. 9. Use of a flavonol derivative containing 1,2,3, 4-tetrahydroquinoline according to claim 1 or 2 for the preparation of a medicament for inhibiting plant pathogenic bacteria.
  10. 10. The use according to claim 9, wherein the plant pathogenic fungi comprise Sclerotinia sclerotiorum (Ss), rhizoctonia cerealis (Ps), anthrax colletotrichum (Cg), rhizoctonia solani (Ab), phytophthora capsici (Pc), gibberella aestiva (Fg), botrytis cinerea (Bc), rhizoctonia solani (Fo), rhizoctonia cerealis (Xoo), rhizoctonia cerealis (Xac), rhizoctonia mangiferum (Xcm), rhizoctonia solani (Pcb).

Description

Flavonol derivative containing 1,2,3, 4-tetrahydroquinoline and preparation method and application thereof Technical Field The invention belongs to the technical field of pesticide synthesis, and particularly relates to a flavonol derivative containing 1,2,3, 4-tetrahydroquinoline, and a preparation method and application thereof. Background Under the dual pressures of continuous population growth and climate change exacerbation, achieving stable and high yields in agriculture faces unprecedented challenges. Among them, diseases caused by plant pathogens are one of the most major biological stress that restricts agricultural production. Although the traditional chemical pesticide has quick effect, the long-term use of the traditional chemical pesticide is easy to cause the problems of enhanced drug resistance of pathogenic bacteria, pesticide residues, environmental pollution and the like. Therefore, it is imperative to explore new approaches for environmental friendly and sustainable plant disease management. The natural products (secondary metabolites) have various structures and rich pharmacological activities, and have the core advantages of environmental friendliness, safety for people and livestock, easy natural degradation, difficult induction of drug resistance and the like in the prevention and treatment of agricultural plant diseases. The research and development of novel pesticides by taking natural products as lead compounds has become a research hotspot in recent years, meets the development requirement of green agriculture, and has important research value and wide application prospect. Flavonols, which are a natural product widely found in vegetables, fruits, grains, beans and medicinal plants, have various biological activities such as antifungal, antiviral, anti-inflammatory, anticancer, etc., and have been used as simple scaffolds in synthetic chemistry. In 2007, lee and the like synthesized a series of flavonol derivatives, and various compounds can inhibit proliferation of various cancer cells with high efficiency, and particularly, the IC 50 with the strongest inhibitory activity on human colon cancer cells (HCT 116) is 0.017 mu mol/L.2021, du et al synthesized a series of 7-isopentenyloxy flavonols and screened for antibacterial activity, and part of the compounds had better inhibitory effect on potato ring rot, the minimum inhibitory concentration reached 0.08 mg/mL, far lower than the lead compound quercetin (the minimum inhibitory concentration was 0.313 mg/mL). The Zhou et al synthesizes a series of flavonol derivatives containing benzoxazole and carries out antiviral tests, and the results show that part of compounds have excellent antiviral activity on Tobacco Mosaic Virus (TMV) in vivo, and the optimal EC 50 values of the treatment and protection activities on TMV are 127.6 and 101.2 mug/mL respectively, which are obviously better than Ningnan mycin (320.0 and 234.6 mug/mL). Extensive literature research has found that the research on common plant pathogen diseases of flavonols on crops is very limited, so that flavonols have further research and application values. 1,2,3, 4-Tetrahydroquinoline and its derivatives are an important class of nitrogen-containing heterocyclic compounds, which are widely found in a variety of natural products. Because of the diverse biological activities and application potential, the method is always a research hot spot in the fields of pharmaceutical chemistry, organic synthesis methodologies, material science and the like. In 2022, zhang et al synthesized a series of novel sulfonyl hydrazide derivatives containing 1,2,3, 4-tetrahydroquinoline and evaluated for antibacterial activity, and the results showed that some compounds had good in vitro activity against Vibrio sclerotinii (S. sclerotiorum) and Vibrio marli (V. mali), with optimal EC 50 values of 3.32 and 2.78 μg/mL, respectively. In 2024, deng et al synthesized a series of chalcone derivatives containing 1,2,3, 4-tetrahydroquinoline, and performed antibacterial activity tests, and the results showed that some compounds had a strong inhibitory effect on Phytophthora capsici (Pc), with an optimal EC 50 value of 5.2 μg/mL, higher than that of the control drugs azoxystrobin (EC 50 =80.2 μg/mL) and fluopyram (EC 50 =146.8 μg/mL). Based on the consideration, the research introduces 1,2,3, 4-tetrahydroquinoline structural units into a flavonol matrix according to the active group splicing principle, designs and synthesizes a series of derivatives with novel structures, and performs in-vitro biological activity screening of a system so as to optimize and obtain flavonol derivatives with higher antibacterial activity, thereby providing a certain theoretical basis for the research of green pesticides and promoting innovation of the green pesticides. Disclosure of Invention The invention aims to provide a flavonol derivative containing 1,2,3, 4-tetrahydroquinoline, and a preparation method and applica