CN117886712A

CN117886712A - Isolamine-containing capsaicin compound, and preparation method and application thereof

Info

Publication number: CN117886712A
Application number: CN202410034694.4A
Authority: CN
Inventors: 杨松; 王娜; 梁鸿; 张太洪; 冯钰梅; 齐普应; 周翔; 柳立伟; 吴志兵; 薛伟
Original assignee: Guizhou University
Current assignee: Guizhou University
Priority date: 2024-01-10
Filing date: 2024-01-10
Publication date: 2024-04-16

Abstract

The invention relates to the technical field of pharmaceutical chemistry, in particular to a capsaicin compound containing isopropanolamine, a preparation method and application thereof, wherein the compound has a structure shown in a general formula (I):

Description

Isolamine-containing capsaicin compound, and preparation method and application thereof

Technical Field

The invention belongs to the technical field of pharmaceutical chemistry, and particularly relates to a capsaicin compound containing isopropanolamine, a preparation method and application thereof.

Background

Bacterial and fungal plant diseases such as bacterial leaf blight of rice, bacterial wilt of capsicum, leaf spot of cabbage, bacterial wilt of tobacco, citrus canker, kiwi fruit canker, gray mold of cucumber, pepper wilt, sclerotium of rape, wheat scab, late blight of potato, root rot of blueberry, chaetomium, anthracnose of dragon fruit, rice sheath blight and the like, can cause the host plant to show symptoms such as necrosis, wilt and rot, bring about huge economic loss to crops in the world each year, and cause crop yield reduction of up to 60% -75% in serious cases. Chemical control is easy to operate, has low cost and is still the most effective mode for controlling the plant, but a series of problems such as environmental pollution, agricultural residues, damage to human health and the like are caused by unreasonable use of traditional pesticides for a long time, and drug resistance of plant pathogenic microorganisms is caused, so that drug-resistant plants are generated. Thus, there is an urgent need to develop a novel bactericide which has high activity, high selectivity and no cross resistance with existing pesticides.

Natural products play an important role in the development of pesticides. It is reported that the novel active ingredient in conventional pesticides is mostly derived from natural products and has a proportion of about 66.4%. In addition, the botanical pesticide has the advantages of being ecological, high in safety, various in action mode, wide in adaptability and the like, and is favored in the research and development of new pesticides. Capsaicin and its derivatives are reported to have a wide range of biological activities, such as antifungal, antibacterial, herbicidal, antitumor, antiviral, etc. At present, various efficient pesticides containing capsaicin structure play an important role in plant disease and pest control. Isopropanolamine structures are widely used in the fields of pesticides and medicines, such as antagonists, bactericides, antihyperglycemic agents, antimalarial agents and the like, and contain the isopropanolamine structure. More importantly, the previous study of the subject group revealed that the isopropanolamine structure-containing derivatives all exhibit excellent antibacterial activity by being able to be linked to different precursor precursors.

In order to find an efficient antibacterial active compound, the invention takes capsaicin as a guide, introduces an isopropanolamine skeleton, designs and synthesizes a series of capsaicin derivatives containing isopropanolamine structures, tests the bioactivity of the capsaicin derivatives, and provides an important scientific basis for the research and development and the creation of new pesticides.

The study of the biological activity of capsaicin compounds has progressed as follows:

akyuz et al [ Akyuz L., kaya M., mujoba M., ilk S., sargin I., salaverria A.M., labidi J., cakmak Y.S., islek C.supporting capsaicin with chitosan-based films enhanced theanti-quorum sensing, anti-biological, tranpany elasticity and hydrophobicity [ J ]. International Journal of Biological Macromolecules,2018,115:438-446 ] found capsaicin to have biological functions of high antioxidant, anti-inflammatory, weight loss, anticancer and analgesic properties, for the first time, for use in membrane technology. Chitosan (as a common animal-based polymer) was blended with capsaicin at three different concentrations to obtain an edible film. Films were characterized by FT-IR, SEM, DSC et al. Mechanical, transmittance, hydrophobicity, anti-quorum sensing, antibacterial and antioxidant properties were also examined. The optimal concentration for enhancing three membrane properties (including mechanical, optical and surface morphology) was observed by incorporating 0.6mg capsaicin into a chitosan matrix (200 mg dissolved in 1% acetic acid solution). As the capsaicin concentration in the film increased, continued improvements in anti-quorum and antimicrobial activity, oxidation resistance and hydrophobicity were noted. In further studies, chitosan-capsaicin blend films are useful as food packaging materials as well as skin and wound healing patches.

In 2020, wang et al [ Rongang Wang, yang Liu, shiwei Sun, yueyue Si, xaoohong Liu, xaoxoian Liu, shuang Zhang,. Capsaicinoids from hot pepper (Capsicum annuum L.) and theirphytotoxic effect on seedling growth of lettuce (Laxuca sativa L.) [ J ]. Natural product research,2020,34,1597-1601 ] isolated a series of capsaicin compounds from Capsicum fruits by semi-preparative high performance liquid chromatography: N-vanillyl-4E, 6E-diene-8-methylnonanamide, capsaicin, dihydrocapsaicin, N-vanillyl octanamide, nordihydrocapsaicin, N-vanillyl decanoamide, homocapsaicin, N-vanillyl-4, 8-dimethylacrylamide homodihydrocapsaicin II, homodihydrocapsaicin II and homodihydrocapsaicin I. The isolated compounds were structurally characterized by comparison of spectroscopic data with literature data. Biological assay results show that the capsaicin compound can obviously shorten the radicle length of lettuce seedlings, and the inhibition effect has dose dependency.

In 2022 Xie et al (Dandan Xie, zaiping Yang, xin Hu, yin Wen. Synthesis, antibacterial, andInsecticidal Activities of Novel Capsaicin Derivatives Containing a Sulfonic Acid Esters Moiety [ J ] front. Chem.2022,10,929050.) developed a series of capsaicin derivatives containing sulfonate structures. Their structure is characterized by nuclear magnetic resonance spectroscopy and high resolution mass spectrometry. The results of biological activity indicate that some target compounds have significant antibacterial activity. At 50 mug/mL, the compound 3b shows the most excellent activity on kiwifruit canker, rice bacterial leaf blight and citrus canker, and the inhibition rates are 86, 54 and 92 percent respectively, which are higher than those of commercial drugs thiabendazole (87, 34 and 77 percent) and bismerthiazol (87, 37 and 75 percent). In addition, although some compounds have some inhibitory effect on the noctuid, they are weaker than the positive control monosultap. Thus, bioassay results suggest that these newly designed and synthesized scaffolds may act as lead compounds for biocidal compounds rather than pesticides.

In 2023 Behbehani et al [ Behbehani J.M., irshad M., shreaz S., karched M. Anti-microbial activity of capsaicin and its effect on ergosterol biosynthesis and membrane integrity of Candidaalbicans [ J ]. International Journal of Molecular Sciences,2023,24,1046 ] studied the antifungal sensitivity of capsaicin as an active ingredient in capsicum. Capsaicin and fluconazole sensitivity to Candida albicans was tested using the CLSI (M27-A3) method. The effect of capsaicin on fungal cell walls was examined by ergosterol inhibition and observed by scanning electron microscopy, with the lowest inhibitory concentration of capsaicin on 30 strains of C.stomatitis, 8 strains of C.dental pulp and 2 strains of ATCC candida ranging from 12.5-50 μg/mL. After combination with capsaicin (MIC/4), the MIC range of fluconazole (128-4. Mu.g/mL) is significantly reduced (2-4 fold). Capsaicin (MIC) significantly reduces the mature biofilm of candida albicans by 70% to 89%. With increasing capsaicin dose, the ergosterol content of the cell wall decreases significantly. Capsaicin exhibits a high sensitivity to hyphal formation, exhibiting a reduction of over 71% in mature biofilms. Fluorescence microscopy revealed a capsaicin-treated candida albicans cell membrane disruption, while electron microscopy images revealed a distorted cell shape, a broken cell wall, and cell shrinkage after release of the cell contents. The results indicate that capsaicin has potential antifungal activity, inhibits ergosterol biosynthesis in the cell wall, and thus disrupts the structure and integrity of the cell. More importantly, capsaicin synergistically enhances the antifungal activity of fluconazole, and the synergistic effect can be helpful for preventing the development of fluconazole drug resistance and reducing the dosage.

Disclosure of Invention

In order to solve the technical problems, the invention provides a capsaicin compound containing isopropanolamine, and a preparation method and application thereof.

In order to achieve the above purpose, the invention provides an isopropanolamine-containing capsaicin compound, which has a structure shown in a general formula (I):

wherein,

R ¹ one or more selected from capsaicin parent C9 alkyl, C9 alkenyl, benzoyl, acetyl, propionyl, butyryl and acryloyl;

R ² and R is ³ Identical or different, R ² And R is ³ Independently selected from one or more of hydrogen, deuterium, optionally substituted or unsubstituted alkyl, optionally substituted or unsubstituted alkenyl, optionally substituted or unsubstituted alkynyl, optionally substituted or unsubstituted alkoxy, optionally substituted or unsubstituted cycloalkyl, optionally substituted or unsubstituted aryl, optionally substituted or unsubstituted heteroaryl.

According to the invention, capsaicin and isopropanolamine structures are taken as pharmacophores, and two pharmacophores are connected through different bridging chains to synthesize a series of capsaicin derivatives containing isopropanolamine, and the compounds have excellent inhibition effects on plant pathogenic bacteria such as bacterial blight bacteria of rice, canker bacteria of citrus, bacterial strip spot bacteria of rice, canker bacteria of kiwi fruits and the like, thus providing an important scientific basis for developing and creating new pesticides.

Preferably, R ² And R is ³ Identical or different, R ² And R is ³ Independently selected from one or more of hydrogen, deuterium, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, substituted or unsubstituted C6-C15 aryl, substituted or unsubstituted C6-C10 heteroaryl;

wherein the substitution refers to substitution with one or more of C1-C6 alkyl, C1-C6 alkoxy, amino, hydroxy, halogen, nitro and trifluoromethyl.

More preferably, R ² And R is ³ Identical or different, R ² And R is ³ Independently selected from:

preferably, the isopropanolamine-containing capsaicin compound is selected from the following compounds:

the invention also provides an intermediate compound for preparing the isopropanolamine-containing capsaicin compound, which has a structural formula shown in formula (II):

R ¹ one or more selected from capsaicin parent C9 alkyl, C9 alkenyl, benzoyl, acetyl, propionyl, butyryl and acryloyl.

The invention also provides a preparation method of the capsaicin compound containing isopropanolamine, which comprises the following synthetic route:

The invention also provides a composition, the active ingredient of which is the capsaicin compound containing isopropanolamine or the stereoisomer thereof, or the salt thereof or the solvate thereof, and the composition also comprises an agriculturally usable auxiliary agent or bactericide, pesticide or herbicide.

Preferably, the formulation of the composition is selected from the group consisting of Emulsifiable Concentrates (EC), powders (DP), wettable Powders (WP), granules (GR), aqueous Solutions (AS), suspensions (SC), ultra low volume sprays (ULV), soluble Powders (SP), microcapsules (MC), smoke agents (FU), aqueous Emulsions (EW) or water dispersible granules (WG).

The invention also provides application of the isopropanolamine-containing capsaicin compound or the composition in the aspect of controlling agricultural diseases and insect pests. Preferably, the agricultural pest is a bacterial or fungal plant disease; more preferably, the agricultural pest is a plant leaf blight and a plant canker; most preferably, the agricultural pest is rice bacterial leaf blight, cucumber bacterial leaf blight, konjak bacterial leaf blight, citrus canker, tobacco bacterial wilt, grape canker, tomato canker, kiwi fruit canker, apple canker, cucumber gray mold, capsicum blight, rape sclerotinia, wheat scab, potato late blight, blueberry root rot, grape vine cavity bacteria, dragon fruit anthracnose or rice sheath blight.

A method for controlling agricultural pests, which comprises allowing the isopropanolamine-containing capsaicin compound or the composition to act on harmful substances or living environments thereof. Preferably, the agricultural pest is a bacterial or fungal plant disease; more preferably, the agricultural pest is rice bacterial leaf blight, cucumber bacterial leaf blight, konjak bacterial leaf blight, citrus canker, tobacco bacterial wilt, grape canker, tomato canker, kiwi canker, apple canker, cucumber gray mold, pepper blight, rape sclerotinia, wheat scab, potato late blight, blueberry root rot, viticola, dragon fruit anthracnose, rice sheath blight or eggplant verticillium wilt.

A method for protecting plants from agricultural pests, allowing said isopropanolamine-containing capsaicin compound or said composition to act on the plants or their living environment.

The term "alkyl" as used herein is intended to include both branched and straight chain saturated hydrocarbon groups having a specified number of carbon atoms. For example "C _1-10 Alkyl "(or alkylene) is intended to mean C1, C2, C3, C4, C5, C6, C7, C8, C9 and C10 alkyl. In addition, e.g. "C _1-6 Alkyl "means an alkyl group having 1 to 6 carbon atoms. Alkyl groups may be unsubstituted or substituted such that one or more of its hydrogen atoms is replaced by another chemical group. Examples of alkyl groups include, but are not limited to, methyl (Me), ethyl (Et), propyl (e.g., n-propyl and isopropyl), butyl (e.g., n-butyl, isobutyl, t-butyl), pentyl (e.g., n-pentyl, isopentyl, neopentyl) and the like.

"alkenyl" is a hydrocarbon that includes both straight or branched chain structures and has one or more carbon-carbon double bonds that occur at any stable point in the chain. For example "C _2-6 Alkenyl "(or alkenylene) is intended to include C2, C3, C4, C5 and C6 alkenyl groups. Examples of alkenyl groups include, but are not limited to, vinyl, 1-propenyl, 2-butenyl, 3-butenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 5-hexenyl, 2-methyl-2-propenyl, 4-methyl-3-pentenyl and the like.

"alkynyl" is a hydrocarbon that includes both straight or branched chain structures and has one or more carbon-carbon triple bonds that occur at any stable point in the chain. For example "C _2-6 Alkynyl "(or alkynylene) is intended to include C2, C3, C4, C5, and C6 alkynyl; such as ethynyl, propynyl, butynyl, pentynyl, hexynyl, and the like.

The term "substituted" as used herein refers to any one or more hydrogen atoms on a specified atom or group being replaced with a selected specified group, provided that the specified atom's general valency is not exceeded. Substituents are named to the central structure, unless otherwise indicated. For example, it is understood that when (cycloalkyl) alkyl is the possible substituent, the point of attachment of the substituent to the central structure is in the alkyl moiety. As used herein, a ring double bond is a double bond formed between two adjacent ring atoms (e.g., c= C, C =n or n=n). When referring to substitution, particularly polysubstituted, it is meant that a plurality of substituents are substituted at various positions on the indicated group, e.g. dichlorophenyl refers to 1, 2-dichlorophenyl, 1, 3-dichlorophenyl, 1, 4-dichlorophenyl and 2, 4-dichlorophenyl.

Combinations of substituents and or variables are permissible only if such combinations result in stable compounds or useful synthetic intermediates. The stable compound or stable structure implies that the compound is sufficiently stable when isolated from the reaction mixture in useful purity, and is formulated to form an effective therapeutic agent. Preferably, the compounds at present do not comprise N-halogen, S (O) ₂ H or S (O) H group.

The term "aryl" refers to a monocyclic or bicyclic aromatic hydrocarbon group having 6 to 12 carbon atoms in the ring portion, such as phenyl and naphthyl, each of which may be substituted.

The term "halogen" or "halogen atom" refers to chlorine, bromine, fluorine and iodine.

The term "haloalkyl" refers to a substituted alkyl group having one or more halogen substituents. For example, "haloalkyl" includes mono-, di-and trifluoromethyl; even though the halo in the haloalkyl is explicitly fluoro, chloro, bromo, iodo, it also refers to substituted alkyl groups having one or more fluoro, chloro, bromo, iodo substituents.

The term "heteroaryl" refers to substituted and unsubstituted aromatic 5-or 6-membered monocyclic groups, 9-or 10-membered bicyclic groups, and 11 to 14-membered tricyclic groups, having at least one heteroatom (O, S or N) in at least one ring, said heteroatom-containing ring preferably having 1,2 or 3 heteroatoms selected from O, S and N. Each ring of the heteroatom-containing heteroaryl group may contain one or two oxygen or sulfur atoms and/or from 1 to 4 nitrogen atoms provided that the total number of heteroatoms in each ring is 4 or less and that each ring has at least one carbon atom. The fused ring completing the bicyclic and tricyclic groups may contain only carbon atoms and may be saturated, partially saturated, or unsaturated. The nitrogen and sulfur atoms may optionally be oxidized and the nitrogen atoms may optionally be quaternized. Bicyclic or tricyclic heteroaryl groups must include at least one wholly aromatic ring and the nitrogen other fused rings may be aromatic or non-aromatic. Heteroaryl groups may be attached at any available nitrogen or carbon atom of any ring. When the valency permits, if the other ring is cycloalkyl or heterocycle, it is additionally optionally substituted with =o (oxygen).

Exemplary monocyclic heteroaryl groups include pyrrolyl, pyrazolyl, pyrazolinyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, thiadiazolyl, furanyl, thienyl, oxadiazolyl, pyridinyl, pyrazinyl, pyrimidinyl, pyridazinyl, triazinyl, and the like.

Exemplary bicyclic heteroaryl groups include indolyl, spirocyclic ketone, benzodioxolyl, benzoxazolyl, benzothienyl, quinolinyl, tetrahydroisoquinolinyl, isoquinolinyl, benzimidazolyl, benzofuranyl, indolizinyl, benzofuranyl, chromonyl, coumarin, benzofuranyl, cinnolinyl, quinoxalinyl, indazolyl, pyrrolopyridinyl, fluoropyridyl, dihydroisoindolyl, tetrahydroquinolinyl, and the like.

The compounds of the present invention are understood to include both the free form and salts thereof, unless otherwise indicated. The term "salt" means an acid and/or base salt formed from inorganic and/or organic acids and bases. In addition, the term "salt" may include zwitterionic (inner salts), such as when the compounds of formula I contain basic moieties such as amine or pyridine or imidazole rings, and acidic moieties such as carboxylic acids. Pharmaceutically acceptable (i.e., non-toxic, physiologically acceptable) salts are preferred, such as acceptable metal and amine salts, wherein the cation does not contribute significantly to the toxicity or bioactivity of the salt. However, other salts may be useful, such as by employing isolation or purification steps in the preparation process, and are therefore also included within the scope of the present invention.

Preferably, C1-C10 alkyl refers to methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl and isomers thereof; C1-C10 alkoxy means methoxy, ethoxy, propoxy, butoxy, pentoxy, hexoxy, heptoxy, octoxy, nonoxy, decyloxy and isomers thereof; C2-C5 alkenyl refers to ethenyl, propenyl, allyl, butenyl, pentenyl and isomers thereof.

When referring to substituents as alkenyl, alkynyl, alkyl, halogen, aryl, heteroaryl, alkoxy, cycloalkyl, hydroxy, amino, mercapto, phosphino, or when referring to such substituents as in particular to a particular alkenyl, alkynyl, alkyl, halogen, aryl, heteroaryl, alkoxy, cycloalkyl, hydroxy, amino, mercapto, phosphino, one to three of the above substituents are meant. For example methylphenyl refers to one to three methyl-substituted phenyl groups.

Compared with the prior art, the invention has the following advantages and technical effects:

the invention synthesizes a series of capsaicin derivatives containing isopropanolamine based on capsaicin compounds, and discovers that the series of compounds have good inhibition effect on plant pathogenic bacteria, have good inhibition effect on pathogenic bacteria (such as rice bacterial blight bacteria (Xanthomonas oryzae pv. Oryzae, xoo), citrus canker bacteria (Xanthomonas axonopodis pv. Citr, xac) and the like), and provide important scientific basis for the research and development and creation of new pesticides.

Detailed Description

Various exemplary embodiments of the invention will now be described in detail, which should not be considered as limiting the invention, but rather as more detailed descriptions of certain aspects, features and embodiments of the invention.

It is to be understood that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. In addition, for numerical ranges in this disclosure, it is understood that each intermediate value between the upper and lower limits of the ranges is also specifically disclosed. Every smaller range between any stated value or stated range, and any other stated value or intermediate value within the stated range, is also encompassed within the invention. The upper and lower limits of these smaller ranges may independently be included or excluded in the range.

Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although only preferred methods and materials are described herein, any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention. All documents mentioned in this specification are incorporated by reference for the purpose of disclosing and describing the methods and/or materials associated with the documents. In case of conflict with any incorporated document, the present specification will control.

It will be apparent to those skilled in the art that various modifications and variations can be made in the specific embodiments of the invention described herein without departing from the scope or spirit of the invention. Other embodiments will be apparent to those skilled in the art from consideration of the specification of the present invention. The specification and examples of the present invention are exemplary only.

As used herein, the terms "comprising," "including," "having," "containing," and the like are intended to be inclusive and mean an inclusion, but not limited to.

The technical means used in the examples are conventional means well known to those skilled in the art unless otherwise indicated. All the starting materials and solvents used in the examples are commercially available products.

The technical scheme of the invention is further illustrated by the following examples.

Example 1 preparation of intermediate 1

Capsaicin analog (5.0 g,0.01704 mol) and anhydrous K ₂ CO ₃ (4.71 g,0.03408 mol) was added to 50mL of N, N-Dimethylformamide (DMF), stirred at room temperature for 10min, thenBromopropane oxide (2.10 mL,0.02556 mol) was added and stirred overnight. Thereafter, 50mL of ethyl acetate was added to the mixture, and the organic layer was saturated with NH ₄ Washing with Cl solution, anhydrous Na ₂ SO ₄ Drying and vacuum evaporating. By column Chromatography (CH) ₂ Cl ₂ /CH ₃ Oh=100:1, V/V) to give pure intermediate 1. White solid, yield 82.28%;

other epoxy intermediate compounds were synthesized using the corresponding starting materials or substituents, with reference to the procedure of example 1.

EXAMPLE 2N- (4- (3- (cyclopropylamino) -2-hydroxypropoxy) -3-methoxybenzyl) nonanamide, the target compound

Intermediate 1 (0.2 g,0.5720 mmol), cyclopropylamine (0.06335 g,1.1400 mol) and isopropanol (6.0 mL) were added to a 15mL pressure bottle and stirred at 60 ℃ until intermediate 1 was fully reacted. The reaction mixture was extracted with water (20 mL), ethyl acetate (30 mL. Times.2), and the organic layer was extracted with anhydrous Na ₂ SO ₄ Drying and vacuum evaporating. Target compound uses CH ₂ Cl ₂ And CH (CH) ₃ OH (10:1; V/V) was used as eluent for column chromatography separation and purification. The title compound 1 was obtained as a white solid in 54.15% yield.

Other target compounds were synthesized using the corresponding starting materials or substituents, according to the procedure of example 2.

The structure and nuclear magnetic resonance hydrogen spectrum and carbon spectrum data of the synthesized capsaicin compound containing isopropanolamine are shown in table 1, and the physicochemical properties are shown in table 2.

Table 1 Nuclear magnetic resonance Hydrogen Spectrometry and carbon Spectrometry data for a portion of the Compounds

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TABLE 2 physicochemical Properties of the target Compounds

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Pharmacological example 1

EC ₅₀ (median effective concentration) is an important index for evaluating the sensitivity of plant pathogenic bacteria to a compound, and is also an important parameter for setting the concentration of the compound when researching the action mechanism of the target compound. In the concentration gradient experiment, proper 5 concentrations are set by adopting a double dilution method, and finally the inhibition rate of the medicament to plant pathogenic bacteria and the medicament concentration are converted into logarithmic values, and the virulence curve is obtained by SPSS software regression analysis, so that EC is calculated ₅₀ 。

Testing the effective medium concentration EC of the target compound to plant pathogenic bacteria by using turbidity method ₅₀ The test subjects were rice bacterial leaf blight bacteria (Xoo), citrus canker bacteria (Xac) and rice bacterial leaf streak (Xoc). DMSO was dissolved in the medium as a blank. Putting rice bacterial leaf blight bacteria (rice bacterial leaf blight pathogenic bacteria are in an M210 solid culture medium) into an NB culture medium, and carrying out shake culture in a constant-temperature shaking table at 28 ℃ and 180rpm until the bacterial leaf blight bacteria are in a logarithmic growth phase for later use; placing citrus canker pathogens (on M210 solid medium) into NB medium; the rice bacterial leaf spot bacteria (on M210 solid medium) are put into NB medium and are shake-cultured in a constant temperature shaker at 28 ℃ and 180rpm until logarithmic phase is ready for use. 5mL of toxic NB liquid culture medium with different concentrations (for example, 100,50,25,12.5,6.25 mug/mL) of the medicament (compound) is prepared, and is added into a test tube, 40 mu L of NB liquid culture medium containing phytopathogenic bacteria is respectively added, and the mixture is oscillated in a constant temperature shaking table at 28-30 ℃ and 180rpm, wherein bacterial leaf blight of rice is cultivated for 48 hours, citrus canker is cultivated for 48 hours, and bacterial leaf spot of rice is cultivated for 48 hours. Measuring OD of bacterial solutions with various concentrations on an enzyme-labeled instrument ₅₉₅ Values, and additionally determining the OD of corresponding concentrations of toxic sterile NB liquid medium ₅₉₅ Values.

Corrected OD = bacteria-containing medium OD-sterile medium OD

Inhibition ratio = [ (corrected control culture medium bacterial liquid OD value-corrected toxic culture medium OD value)/corrected control culture medium bacterial liquid OD value ] ×100

The present invention is described with the aid of examples, but the contents of examples are not limited thereto, and the experimental results of the target compounds are shown in table 3.

TABLE 3 EC of isopropanolamine-containing capsaicin against phytopathogenic bacteria ₅₀

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As can be seen from Table 3, the target compounds showed good inhibitory activity against plant pathogenic bacteria (such as Rhizoctonia solani, rhizoctonia cerealis and Rhizoctonia cerealis) in an in vitro test. In particular, the compounds 26, 25, 19 and 18 have extremely excellent activity against bacterial leaf blight of rice, and EC thereof ₅₀ 9.91-18.71 mug/mL; compounds 26, 18, 16 have extremely excellent activity against citrus canker pathogens, their EC ₅₀ 7.04-15.40 mug/mL; compound 27 exhibits excellent inhibitory activity against Pyricularia oryzae and EC thereof ₅₀ 22.00. Mu.g/mL. Therefore, the compound has great research prospect and can be used for preparing pesticides against plant pathogenic bacteria.

Pharmacological example 2 test of the inhibition of in vitro antibacterial efficacy of Compound 26 against phytopathogenic fungi Using the hyphal growth Rate method

The test subjects of the fungus, botrytis cinerea, rhizoctonia solani, sclerotinia sclerotiorum, verticillium eggplant verticillium and Gibberella wheat take DMSO in sterile distilled water as negative control, and boscalid as positive control.

2.1 Compound 26 was dissolved in DMSO (1.0 mL), then added to 9.0mL of sterile water containing Tween 20 (1%) and then mixed with potato dextrose agar (PDA, 90.0 mL) at a concentration of 25mg/L of Compound 26.

2.2 the stock solution was transferred uniformly to three 9cm diameter petri dishes.

2.3 mycelium dishes of approximately 4mm diameter were then cut from the medium and inoculated aseptically in the middle of the PDA plates.

2.4 plates after inoculation were incubated at 27.+ -. 1 ℃ for 3-5 days with 3 replicates per treatment condition.

2.5 radial growth of fungal colonies was measured and data were statistically analyzed. The bacteriostatic effect was calculated as = [ (C-T)/(C-0.4) ]x100%, where C is the diameter of fungal growth on untreated PDA, T is the diameter of fungal growth on treated PDA, and I is the rate of inhibition.

The present invention is described with the aid of examples, but the contents of examples are not limited thereto, and the experimental results of the target compounds are shown in table 4.

Table 4 inhibition of in vitro antibacterial efficacy of Compound 26 against phytopathogenic fungi, phytophthora capsici, rhizoctonia cerealis, sclerotinia sclerotiorum, verticillium eggplant and Alternaria wheat (percent)

As can be seen from Table 4, compound 26 was inactive against all six phytopathogenic fungi tested at 25mg/L, but the literature reports that compounds containing capsaicin fragments have activity against phytopathogenic fungi, and it can be considered later that the introduction of other active fragments to increase the antifungal activity of the series of compounds broadens its broad spectrum.

The foregoing is merely a preferred embodiment of the present application, but the scope of the present application is not limited thereto, and any changes or substitutions easily conceivable by those skilled in the art within the technical scope of the present application should be covered in the scope of the present application. Therefore, the protection scope of the present application shall be subject to the protection scope of the claims.

Claims

1. An isopropanolamine-containing capsaicin compound is characterized by having a structure shown in a general formula (I):

wherein,

2. Isopropanolamine-containing capsaicinoids according to claim 1, wherein R ² And R is ³ Identical or different, R ² And R is ³ Independently selected from one or more of hydrogen, deuterium, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, substituted or unsubstituted C6-C15 aryl, substituted or unsubstituted C6-C10 heteroaryl;

3. Isopropanolamine-containing capsaicinoids according to claim 2, wherein R ² And R is ³ Identical or different, R ² And R is ³ Independently selected from:

4. the isopropanolamine-containing capsaicin compound according to claim 1, selected from the following compounds:

5. an intermediate compound for preparing the isopropanolamine-containing capsaicin compound according to any one of claims 1-4, wherein the structural formula is shown in formula (II):

6. A process for the preparation of the isopropanolamine-containing capsaicin according to any one of claims 1-4, wherein the synthetic route is as follows:

7. A composition comprising as an active ingredient the isopropanolamine-containing capsaicin compound or its stereoisomer or its salt or its solvate according to any one of claims 1 to 4.

8. Use of the isopropanolamine-containing capsaicin compound according to any one of claims 1-4 or the composition according to claim 7 for controlling agricultural pests.

9. A method for controlling agricultural pests, characterized in that the isopropanolamine-containing capsaicin compound according to any one of claims 1 to 4 or the composition according to claim 7 is allowed to act on pests or their living environment.

10. A method for protecting plants from agricultural pests, characterized in that an isopropanolamine-containing capsaicin compound according to any one of claims 1-4 or a composition according to claim 7 is allowed to act on plants or their living environment.