CN-121991045-A - Indole-containing formononetin derivative and preparation method and application thereof

CN121991045ACN 121991045 ACN121991045 ACN 121991045ACN-121991045-A

Abstract

The invention discloses an indole-containing formononetin derivative, and a preparation method and application thereof, and belongs to the technical field of pesticide synthesis. According to the invention, indole groups with good biological activity are introduced into a formononetin structure, a series of indole-containing formononetin derivatives are designed and synthesized, and the synthesized indole-containing formononetin derivatives are subjected to a test for inhibiting activity of plant pathogenic bacteria, so that the derivatives can effectively inhibit various plant pathogenic fungi, and particularly show the strongest inhibition activity on the phomopsis of kiwi fruits.

Inventors

XUE WEI
HAO GEFEI
YANG HAN
FAN JINPING
SHEN DAN
HU QINGXUE
TIAN FANG
XIN LANG
YANG YING
ZHANG HONGYU

Assignees

贵州大学
贵阳市农产品质量安全监督检验测试中心

Dates

Publication Date: 20260508
Application Date: 20260203

Claims (8)

1. An indole-containing formononetin derivative is characterized by having the following structural formula: ; Wherein R is independently selected from H, one or more halogens, one or more nitro groups, one or more C1-C6 alkyl groups, or C1-C6 alkoxy groups.
2. A process for the preparation of an indole-containing formononetin derivative according to claim 1, characterised in that the steps comprise: (1) Indole and epoxybromopropylalkane are used as raw materials, sodium hydride is used as a catalyst, heating reflux reaction is carried out in a solvent, dichloromethane is used for extraction after the reaction is finished, and an extract liquid is evaporated to dryness, so that an intermediate a is obtained; the structural formula of the epoxy bromopropylalkane is as follows: ; the structural formula of the intermediate a is as follows: ; (2) Taking formononetin and epoxybromopropylalkane as raw materials, taking anhydrous potassium carbonate as a catalyst, reacting at normal temperature, adding ice water after the reaction is finished to separate out a product, filtering, and removing impurities from filter residues to obtain an intermediate b; The structural formula of the intermediate b is as follows: ; (3) Taking the intermediate b and piperazine as raw materials, taking anhydrous potassium carbonate as a catalyst, heating and refluxing in a solvent for reaction, adding ice water after the reaction is finished to separate out a product, filtering, and removing impurities from filter residues to obtain an intermediate c; the structural formula of the intermediate c is as follows: ; (4) And (3) taking the intermediate c and the intermediate a as raw materials, taking anhydrous potassium carbonate as a catalyst, heating and refluxing in a solvent, adding ice water after the reaction is finished to separate out a product, filtering, and removing impurities from filter residues to obtain the formononetin derivative containing indole.
3. The preparation method according to claim 2, wherein the molar ratio of indole, epoxybromopropylalkane and sodium hydride in the step (1) is 12.8:25.6:25.6, the temperature of the heating reaction is 80 ℃, the reaction time is 2-5h, and the solvent is N-N-dimethylformamide.
4. The preparation method of the composition according to claim 2, wherein in the step (2), the molar ratio of the formononetin to the epoxybromopropylalkane to the anhydrous potassium carbonate is 18.6:37.3:55.9, the reaction time is 1d, the solvent is N-N-dimethylformamide, and the impurity removal step comprises washing filter residues with water and petroleum ether in sequence, standing and filtering to finish washing.
5. The preparation method of the catalyst according to claim 2, wherein in the step (3), the molar ratio of the intermediate b to the piperazine to the anhydrous potassium carbonate is 6.2:20.4:18.5, the reaction temperature is 80 ℃, the reaction time is 2-4 hours, the solvent is isopropanol, and the impurity removal step comprises washing filter residues with water and petroleum ether in sequence, and then standing and filtering to finish washing.
6. The preparation method according to claim 2, wherein in the step (4), the molar ratio of the intermediate C to the intermediate a to the anhydrous potassium carbonate is 2.44:4.4:7.3, the temperature of the heating reaction is 80 ℃, the reaction time is 2-4h, the solvent is isopropanol, and the step of removing impurities comprises washing filter residues with water and petroleum ether in sequence, then standing and filtering to finish washing.
7. Use of an indole-containing formononetin derivative according to claim 1 for the preparation of a medicament for inhibiting phytopathogenic fungi.
8. The use according to claim 7, wherein the plant pathogenic fungi comprise phomopsis kiwi fruit, ps, phytophthora capsici, pc, colletotrichum capsici, cg, sheath blight germ, rs, gibberella wheat, fg, black spot germ of chinese cabbage, ab, fusarium oxysporum, foc, fusarium oxysporum, fo, sclerotium rot germ of colza, ss.

Description

Indole-containing formononetin derivative and preparation method and application thereof Technical Field The invention belongs to the technical field of pesticide synthesis, and particularly relates to an indole-containing formononetin derivative, and a preparation method and application thereof. Background Crop diseases affect the yield and quality of crops all the time, and the crop diseases cause serious loss to grain economy, and the crop diseases are rapidly transmitted and easily generate drug resistance, so that the crop diseases form a serious challenge for chemical control, and the pesticide resistance of pathogenic bacteria is widely developed due to long-term dependence on the traditional chemical bactericides, so that the problems of environmental residues and ecological safety are also brought. Therefore, the development of a novel antibacterial agent which has high efficiency, low toxicity, good environmental compatibility and difficult generation of drug resistance is an urgent need and an important research direction in the field of modern agriculture sustainable development, and the development of a plant source green pesticide with high efficiency and low toxicity is regarded as a very promising path. Among the many active molecules of plant origin, isoflavonoids are of interest due to their broad biological activity and low ecotoxicity, formononetin (Formononetin, 7-hydroxy-4' -methoxyisoflavone), an important isoflavone in leguminous plants, and is widely found in a variety of medicinal plants such as astragalus membranaceus, red clover, kudzuvine root and the like. Modern pharmacological studies have proved that it has not only antioxidant, anti-inflammatory, anticancer, antitumor and anti-lipid peroxidation effects, but also effects of improving atherosclerosis, inhibiting abnormal proliferation of vascular smooth muscle cells, regulating glycolipid metabolism, resisting osteoporosis and aging. In 2021, cui et al reported that formononetin has remarkable antiviral activity against Feline Calicivirus (FCV), with a minimum inhibitory concentration (EC 50) of 13.6 μmol/L. In 2023, jia et al synthesized a series of formononetin derivatives and tested their anticancer and antitumor activities, and the results showed that some of the compounds showed strong inhibitory activity against non-small cell lung cancer a549 cells with a minimum inhibitory concentration (IC 50) of 0.87 μmol/L.2025, luo et al designed a series of formononetin derivatives and evaluated their neuroprotective activity and mechanism of action in N2a/APP695 cell models, and showed that some compounds could clear abnormal protein deposition and alleviate neurotoxicity. 2025 Fu and the like synthesized a series of formononetin derivatives, and performed antibacterial activity test and action mechanism research, and the results show that most of the compounds have good antibacterial activity on phytophthora capsici (Phytophthora capsica), and the minimum antibacterial concentration (EC 50) is 4.2 mug/mL. Numerous literature studies and reports focus on medical targets, but few studies and reports on formononetin and derivatives thereof aiming at plant pathogenic bacteria in the pesticide field exist, and a huge exploration space exists for structural optimization and activity improvement. Indole is taken as a nitrogen-containing aromatic heterocyclic compound, is a core skeleton in natural products and drug molecules, is widely applied to life basic substances (such as amino acid tryptophan, neurotransmitter serotonin, phytohormone indole-3-acetic acid and the like), shows multiple pharmacological activities such as antibiosis, antivirus, antitumor and the like due to the unique chemical structure and wide biological activity of indole in the field of pharmaceutical chemistry, and is also proved to be capable of endowing molecules with excellent sterilization and disinsection performances in pesticide research and development. The structure modification sites are rich, and the derivatization and transformation are easy, so that the modified structure becomes an important pharmacophore for optimizing the activity, selectivity and physicochemical properties of the lead compound. In view of the above, there is no synthesis of indole-containing formononetin derivatives by introducing indole into the formononetin structure, nor has there been an investigation of agricultural activity using indole-containing formononetin derivatives. Disclosure of Invention The invention aims to provide an indole-containing formononetin derivative, and a preparation method and application thereof. The provided indole-containing formononetin derivative can be used for inhibiting plant pathogenic fungi, in particular to phomopsis actinidia. In order to achieve the above purpose, the present invention provides the following technical solutions: according to one of the technical schemes, the invention provides an indole-containing formononetin derivati