A capsaicin compound containing isopropanolamine and a preparation method and application thereof

Abstract

This invention relates to the field of medicinal chemistry, specifically to a capsaicin-like compound containing isopropanolamine, its preparation method, and its application. This type of compound has a structure as shown in general formula (I). The invention uses capsaicin and isopropanolamine as pharmacophores, connecting the two pharmacophores with different bridging chains to synthesize a series of capsaicin-like derivatives containing isopropanolamine. These compounds exhibit excellent inhibitory effects on plant pathogenic bacteria such as rice bacterial blight, citrus canker, rice bacterial leaf streak, and kiwifruit canker; and plant pathogenic fungi such as cucumber gray mold, pepper wilt, rapeseed sclerotinia rot, eggplant verticillium wilt, wheat scab, potato late blight, blueberry root rot, grape coccidioidomyces, dragon fruit anthracnose, and rice sheath blight, providing an important scientific basis for the research and development of new pesticides.

Description

Technical Field

[0001] This invention belongs to the field of medicinal chemistry technology, specifically relating to a capsaicin compound containing isopropanolamine, its preparation method, and its application. Background Technology

[0002] Bacterial and fungal diseases of plants, such as bacterial blight of rice, bacterial wilt of pepper, leaf spot of cabbage, bacterial wilt of tobacco, citrus canker, kiwi canker, gray mold of cucumber, wilt of pepper, sclerotinia sclerotinia of rapeseed, scab of wheat, late blight of potato, root rot of blueberry, spore-forming fungus of grape, anthracnose of dragon fruit, and sheath blight of rice, cause host plants to exhibit symptoms such as necrosis, wilting, and rotting, resulting in huge economic losses to crops worldwide every year, causing yield reductions of up to 60%-75% in severe cases. Chemical control remains the most effective method of control due to its ease of operation and low cost. However, the long-term irrational use of traditional pesticides has led to a series of problems, including environmental pollution, agricultural residues, and harm to human health, and has also resulted in pesticide resistance in plant pathogens, leading to pesticide-resistant plants. Therefore, there is an urgent need to develop new fungicides with high activity, high selectivity, and no cross-resistance with existing pesticides.

[0003] Natural products play a crucial role in pesticide development. It has been reported that the majority of new active ingredients in conventional pesticides are derived from natural products, accounting for approximately 66.4%. Furthermore, plant-derived pesticides are favored in new pesticide development due to their eco-friendliness, high safety, diverse modes of action, and wide adaptability. According to literature, capsaicin and its derivatives possess a wide range of biological activities, such as antifungal, antibacterial, herbicidal, antitumor, and antiviral activities. Currently, several highly effective pesticides containing capsaicin structures are playing an important role in the control of plant diseases and pests. The isopropanolamine structure is widely used in pesticides and pharmaceuticals; for example, antagonists, fungicides, anti-hyperglycemic agents, and antimalarial agents all contain this structure. More importantly, our previous research has found that derivatives containing the isopropanolamine structure exhibit excellent antibacterial activity by being able to connect with different leader compounds.

[0004] In order to find highly effective antibacterial active compounds, this invention uses capsaicin as a lead compound, introduces an isopropanolamine skeleton, designs and synthesizes a series of capsaicin derivatives containing isopropanolamine structures, tests their bioactivity, and provides an important scientific basis for the research and development and creation of new pesticides.

[0005] The following is a summary of the research progress on the bioactivity of capsaicin compounds:

[0006] In 2018, Akyuz et al. [Akyuz L., Kaya M., Mujtaba M., Ilk S., Sargin I., Salaberria AM, Labidi J., Cakmak YS, Islek C. Supplementing capsaicin with chitosan-based films enhanced the anti-quorum sensing, antimicrobial, antioxidant, transparency, elasticity and hydrophobicity[J]. International Journal of Biological Macromolecules, 2018, 115: 438-446.] discovered that capsaicin possesses biological functions such as high antioxidant, anti-inflammatory, weight-loss, anticancer, and analgesic properties, and was used for the first time in membrane technology. Chitosan (as a versatile animal-based polymer) was blended with capsaicin at three different concentrations to obtain edible films. The films were characterized by FT-IR, SEM, DSC, etc. Mechanical properties, transmittance, hydrophobicity, anti-quorum sensing, antibacterial, and antioxidant properties were also examined. Incorporating 0.6 mg of capsaicin into a chitosan matrix (200 mg dissolved in 1% acetic acid solution) revealed the optimal concentration for enhancing three membrane properties, including mechanical, optical, and surface morphology. With increasing capsaicin concentration in the membrane, a sustained improvement in anti-quorum sensing and antimicrobial activity, antioxidant properties, and hydrophobicity was recorded. Further research suggests that chitosan-capsaicin blend membranes could be used as food packaging materials and as skin and wound healing patches.

[0007] In 2020, Wang et al. [Rongrong Wang, Yang Liu, Shiwei Sun, Yueyue Si, Xiaohong Liu, Xiaoxiao Liu, Shuang Zhang,. Capsaicinoids from hot pepper (Capsicum annuum L.) and their phytotoxic effect on seedling growth of lettuce (Lactuca sativa L.)[J]. Natural product research, 2020, 34, 1597-1601.] isolated a series of capsaicinoids from pepper fruits using semi-preparative high-performance liquid chromatography (HPLC): N-vanillyl-4E,6E-diene-8-methylnonanoamide, capsaicin, dihydrocapsaicin, N-vanillyloctamide, nordihydrocapsaicin, N-vanillyldecamide, homocapsaicin, N-vanillyl-4,8-dimethylnonanoamide homodihydrocapsaicin II, homodihydrocapsaicin II, and homodihydrocapsaicin I. The structures of the isolated compounds were characterized by comparison of spectral data and literature data. Bioassay results showed that capsaicin compounds significantly shortened the length of the radicle of lettuce seedlings, and this inhibitory effect was dose-dependent.

[0008] In 2022, Xie et al. [Dandan Xie, Zaiping Yang, Xin Hu, Yin Wen. Synthesis, Antibacterial, and Insecticidal 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 ester structures. Their structures were characterized by nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry. Bioactivity results showed that some target compounds exhibited significant antibacterial activity. At 50 μg / mL, compound 3b showed the best activity against *Actinidia kiwifruit* causal agent, *Bacillus thuringiensis* causal agent, and *Actinidia citrus* causal agent, with inhibition rates of 86%, 54%, and 92%, respectively, higher than the commercial drugs thiabendazole (87%, 34%, and 77%) and tebuconazole (87%, 37%, and 75%). Furthermore, although some compounds showed some inhibitory effect on the brown armyworm, it was weaker than the positive control insecticide. Therefore, the bioassay results suggest that these newly designed and synthesized scaffolds could serve as lead compounds for fungicides rather than insecticides.

[0009] In 2023, Behbehani et al. [Behbehani JM, Irshad M., Shreaz S., Karched M. Anticandidal activity of capsaicin and its effect on ergosterol biosynthesis and membrane integrity of Candida albicans[J]. International Journal of Molecular Sciences, 2023, 24, 1046.] studied the antifungal susceptibility of capsaicin, the active ingredient in chili peppers. The susceptibility of capsaicin and fluconazole to Candida albicans was detected using the CLSI (M27-A3) method. The effect of capsaicin on the fungal cell wall was detected using the ergosterol inhibition method, and scanning electron microscopy was used to observe that the minimum inhibitory concentration (MIC) of capsaicin against 30 strains of oral Candida, 8 strains of dental pulp Candida, and 2 strains of ATCC Candida ranged from 12.5 to 50 μg / mL. When combined with capsaicin (MIC / 4), the MIC range of fluconazole (128-4 μg / mL) was significantly reduced (2-4 times). Capsaicin (MIC) significantly reduced the mature biofilm of *Candida albicans* by 70% to 89%. With increasing capsaicin dosage, the ergosterol content in the cell wall decreased significantly. Capsaicin exhibited high sensitivity to hyphal formation, showing a reduction of over 71% in mature biofilms. Fluorescence microscopy revealed cell membrane rupture in capsaicin-treated *Candida albicans*, while electron microscopy showed distorted cell shape, cell wall rupture, and cell shrinkage after release of cell contents. These results indicate that capsaicin possesses potential antifungal activity by inhibiting ergosterol biosynthesis in the cell wall, thereby disrupting cell structure and integrity. More importantly, capsaicin synergistically enhanced the antifungal activity of fluconazole; this synergistic effect may help prevent the development of fluconazole resistance and reduce dosage. Summary of the Invention

[0010] To address the aforementioned technical problems, this invention proposes a capsaicin compound containing isopropanolamine, its preparation method, and its application.

[0011] To achieve the above objectives, the present invention provides a capsaicin compound containing isopropanolamine, having a structure as shown in general formula (I):

[0012]

[0013] in,

[0014] R 1 It is selected from one or more of the C9 alkyl, C9 alkenyl, benzoyl, acetyl, propionyl, butyryl and acryloyl groups of the capsaicin parent compound;

[0015] R 2 and R 3 Same or different, R 2 and R 3 It is independently selected from one or more of hydrogen, deuterium, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted alkoxy, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl.

[0016] This invention uses capsaicin and isopropanolamine as pharmacophores, and connects the two pharmacophores with different bridging chains to synthesize a series of capsaicin derivatives containing isopropanolamine. These compounds have excellent inhibitory effects on plant pathogenic bacteria such as rice bacterial blight, citrus canker, rice bacterial leaf streak, and kiwifruit canker, providing an important scientific basis for the research and development and creation of new pesticides.

[0017] Preferred, R 2 and R 3 Same or different, R 2 and R 3 It is 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, and substituted or unsubstituted C6-C10 heteroaryl;

[0018] The substitution refers to substitution by one or more of C1-C6 alkyl, C1-C6 alkoxy, amino, hydroxyl, halogen, nitro and trifluoromethyl.

[0019] More preferably, R 2 and R 3 Same or different, R 2 and R 3 Selected independently from:

[0020]

[0021] Preferably, the capsaicin compound containing isopropanolamine is selected from the following compounds:

[0022]

[0023] The present invention also provides an intermediate compound for preparing the isopropanolamine-containing capsaicin compounds, the structural formula of which is shown in formula (II):

[0024]

[0025] R 1It is selected from one or more of the capsaicin parent compounds C9 alkyl, C9 alkenyl, benzoyl, acetyl, propionyl, butyryl, and acryloyl.

[0026] This invention also provides a method for preparing the capsaicin-like compound containing isopropanolamine, the synthetic route of which is as follows:

[0027]

[0028] R 1 It is selected from one or more of the C9 alkyl, C9 alkenyl, benzoyl, acetyl, propionyl, butyryl and acryloyl groups of the capsaicin parent compound;

[0029] R 2 and R 3 Same or different, R 2 and R 3 It is independently selected from one or more of hydrogen, deuterium, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted alkoxy, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl.

[0030] The present invention also provides a composition in which the active ingredient is the capsaicin compound containing isopropanolamine or its stereoisomer, or its salt or its solvate, and the composition further includes agricultural adjuvants or fungicides, insecticides or herbicides.

[0031] Preferably, the dosage form of the composition is selected from emulsifiable concentrate (EC), powder (DP), wettable powder (WP), granules (GR), aqueous solution (AS), suspension concentrate (SC), ultra-low volume spray (ULV), soluble powder (SP), microcapsule (MC), fumigant (FU), emulsion (EW), or water-dispersible granules (WG).

[0032] This invention also provides the application of the capsaicin compounds containing isopropanolamine or the compositions thereof in the prevention and control of agricultural pests and diseases. Preferably, the agricultural pests and diseases are bacterial or fungal plant diseases; more preferably, the agricultural pests and diseases are plant leaf blight and plant canker; most preferably, the agricultural pests and diseases are rice bacterial leaf blight, cucumber bacterial leaf blight, konjac bacterial leaf blight, citrus canker, tobacco bacterial wilt, grape canker, tomato canker, kiwifruit canker, apple canker, cucumber gray mold, pepper wilt, rapeseed sclerotinia stem rot, wheat scab, potato late blight, blueberry root rot, grape cysticercosis, dragon fruit anthracnose, or rice sheath blight.

[0033] A method for controlling agricultural pests and diseases involves applying the capsaicin-like compound containing isopropanolamine or the composition to the harmful substance or its habitat. Preferably, the agricultural pests and diseases are bacterial or fungal plant diseases; more preferably, the agricultural pests and diseases are rice bacterial leaf blight, cucumber bacterial leaf blight, konjac bacterial leaf blight, citrus canker, tobacco bacterial wilt, grape canker, tomato canker, kiwifruit canker, apple canker, cucumber gray mold, pepper wilt, rapeseed sclerotinia stem rot, wheat scab, potato late blight, blueberry root rot, grape cysticercosis, dragon fruit anthracnose, rice sheath blight, or eggplant verticillium wilt.

[0034] A method for protecting plants from agricultural pests and diseases, wherein the capsaicin compound containing isopropanolamine or the composition is applied to the plant or its living environment.

[0035] The term "alkyl" as used here refers to both branched and straight-chain saturated hydrocarbon groups having a specific number of carbon atoms. For example, "C 1-10 Alkyl (or alkylene) refers to C1, C2, C3, C4, C5, C6, C7, C8, C9, and C10 alkyl groups. Additionally, for example, "C 1-6 "Alkyl" means an alkyl group having 1 to 6 carbon atoms. Alkyl groups can be unsubstituted or substituted, such that one or more of their hydrogen atoms are replaced by other chemical groups. Examples of alkyl groups include, but are not limited to, methyl (Me), ethyl (Et), propyl (such as n-propyl and isopropyl), butyl (such as n-butyl, isobutyl, tert-butyl), pentyl (such as n-pentyl, isopentyl, neopentyl) and the like.

[0036] "Alkenyl" refers to hydrocarbons that include both straight-chain and branched structures and have one or more carbon-carbon double bonds that appear at any stable point in the chain. For example, "C 2-6 The term "alkenyl" (or "alkenylidene") aims to include C2, C3, C4, C5, and C6 alkenyl groups. Examples of alkenyl groups include, but are not limited to, vinyl, 1-propenyl, 2-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 their analogues.

[0037] "Alkyne" refers to hydrocarbons that can be either straight-chain or branched and have one or more carbon-carbon triple bonds that appear at any stable point in the chain. For example, "C 2-6 The purpose of "alkynyl" (or ynylene) is to include C2, C3, C4, C5 and C6 alkynyl groups; such as ethynyl, propynyl, butynyl, pentylyl, hexynyl and their analogues.

[0038] The term "substituted" as used herein refers to the substitution of one or more hydrogen atoms on a specified atom or group by a chosen specified group, provided that the substitution does not exceed the general valence of the specified atom. Unless otherwise specified, substituents are named to the central structure. For example, it can be understood that when (cycloalkyl)alkyl is a possible substituent, the substituent's connection point to the central structure is within the alkyl moiety. Cyclic double bonds as used herein are double bonds formed between two adjacent ring atoms (e.g., C=C, C=N, or N=N). When substitution is mentioned, especially polysubstitution, it refers to the substitution of multiple substituents at various positions on a specified group, such as dichlorophenyl referring to 1,2-dichlorophenyl, 1,3-dichlorophenyl, 1,4-dichlorophenyl, and 2,4-dichlorophenyl.

[0039] Combinations of substituents and / or variables are permitted only when these combinations yield stable compounds or useful synthetic intermediates. A stable compound or stable structure implies that the compound is sufficiently stable to be isolated from the reaction mixture with useful purity, subsequently formulated to form an effective therapeutic agent. Preferably, the compound currently does not contain N-halogens, S(O)₂H, or S(O)H groups.

[0040] The term "aryl" refers to a monocyclic or bicyclic aromatic hydrocarbon group, such as phenyl and naphthyl, having 6 to 12 carbon atoms in the ring moiety, each of which can be substituted.

[0041] The term "halogen" or "halogen atom" refers to chlorine, bromine, fluorine, and iodine.

[0042] The term "haloalkyl" refers to a substituted alkyl group having one or more halogen substituents. For example, "haloalkyl" includes mono, bis, and trifluoromethyl groups; even if the halogen in a haloalkyl group is explicitly defined as fluorine, chlorine, bromine, or iodine, it still refers to a substituted alkyl group having one or more fluorine, chlorine, bromine, or iodine substituents.

[0043] 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, wherein the heteroatom-containing ring preferably has 1, 2, or 3 heteroatoms selected from O, S, and N. Each ring of a heteroatom-containing heteroaryl may contain one or two oxygen or sulfur atoms and / or 1 to 4 nitrogen atoms, provided that the total number of heteroatoms in each ring is 4 or less, and each ring has at least one carbon atom. The fused rings completing the bicyclic and tricyclic groups may contain only carbon atoms and may be saturated, partially saturated, or unsaturated. Nitrogen and sulfur atoms may optionally be oxidized, and nitrogen atoms may optionally be quaternized. Bicyclic or tricyclic heteroaryl groups must include at least one fully aromatic ring, and the other fused rings may be aromatic or non-aromatic. Heteroaryl groups may be attached to any available nitrogen or carbon atom in any ring. Where valence permits, if the other ring is a cycloalkyl or heterocyclic ring, it may optionally be substituted with =O (oxygen).

[0044] Exemplary monocyclic heteroaryl groups include pyrrole, pyrazolyl, pyrazolinyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, thiadiazolyl, furanyl, thiophenyl, oxadiazolyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, triazinyl, and their analogues.

[0045] Exemplary bicyclic heteroaryl groups include indole, spirochetone, benzodioxazolyl, benzoxazolyl, benzothiophene, quinolinyl, tetrahydroisoquinolinyl, isoquinolinyl, benzimidazolyl, benzofuranyl, indoleazinyl, benzofuranyl, chromone, coumarinyl, benzofuranyl, cinolinyl, quinoxalinyl, indazole, pyrrolopyridyl, fluoropyridyl, dihydroisoindole, tetrahydroquinolinyl, and their analogues.

[0046] Unless otherwise specified, the compounds of this invention are understood to include both their free state and their salts. The term "salt" means an acidic and / or basic salt formed from an inorganic and / or organic acid and base. Additionally, the term "salt" may include zwitterions (internal salts), such as when a compound of formula I contains a basic segment such as an amine or pyridine or imidazole ring, and an acidic segment such as a carboxylic acid. Pharmaceutically acceptable (i.e., non-toxic, physiologically acceptable) salts are preferred, such as acceptable metal and amine salts, wherein the cation does not significantly contribute to toxicity or the biological activity of the salt. However, other salts may be useful, such as those prepared using separation or purification steps, and are therefore also included within the scope of this invention.

[0047] Preferably, C1-C10 alkyl refers to methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl and their isomers; C1-C10 alkoxy refers to methoxy, ethoxy, propoxy, butoxy, pentoxy, hexoxy, heptoxy, octoxy, nonoxy, decoxy and their isomers; C2-C5 alkenyl refers to vinyl, propenyl, allyl, butenyl, pentenyl and their isomers.

[0048] When referring to substituents as alkenyl, alkynyl, alkyl, halogen, aryl, heteroaryl, alkoxy, cycloalkyl, hydroxyl, amino, mercapto, or phosphinyl, or when these substituents specifically refer to a particular alkenyl, alkynyl, alkyl, halogen, aryl, heteroaryl, alkoxy, cycloalkyl, hydroxyl, amino, mercapto, or phosphinyl group, it refers to one to three of the aforementioned substituents. For example, methylphenyl refers to a phenyl group with one to three methyl-substituted groups.

[0049] Compared with the prior art, the present invention has the following advantages and technical effects:

[0050] This invention is based on capsaicin compounds, synthesizing a series of capsaicin derivatives containing isopropanolamine. It was discovered that this series of compounds exhibits good inhibitory effects against plant pathogenic bacteria, including *Xanthomonas oryzae* pv. oryzae (Xoo) and *Xanthomonas axonopodis* pv. citri (Xac), providing an important scientific basis for the research and development of new pesticides. Detailed Implementation

[0051] Various exemplary embodiments of the present invention will now be described in detail. This detailed description should not be considered as a limitation of the present invention, but rather as a more detailed description of certain aspects, features, and embodiments of the present invention.

[0052] It should be understood that the terminology used in this invention is merely for describing particular embodiments and is not intended to limit the invention. Furthermore, with respect to numerical ranges in this invention, it should be understood that each intermediate value between the upper and lower limits of the range is also specifically disclosed. Every smaller range between any stated value or intermediate value within a stated range, and any other stated value or intermediate value within said range, is also included in this invention. The upper and lower limits of these smaller ranges may be independently included or excluded from the range.

[0053] Unless otherwise stated, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. While only preferred methods and materials have been described herein, any methods and materials similar or equivalent to those described herein may be used in the implementation or testing of this invention. All references to this specification are incorporated by way of citation to disclose and describe methods and / or materials associated with those references. In the event of any conflict with any incorporated reference, the content of this specification shall prevail.

[0054] Various modifications and variations can be made to the specific embodiments described in this specification without departing from the scope or spirit of the invention, as will be apparent to those skilled in the art. Other embodiments derived from this specification will also be readily apparent to those skilled in the art. This specification and embodiments are merely exemplary.

[0055] The terms “include,” “including,” “have,” “contain,” etc., used in this article are all open-ended terms, meaning that they include but are not limited to.

[0056] Unless otherwise specified, the techniques used in the examples are conventional methods well known to those skilled in the art. All raw materials and solvents used in the examples are commercially available products.

[0057] The technical solution of the present invention will be further illustrated by the following embodiments.

[0058] Preparation of Intermediate 1 in Example 1

[0059] Capsaicin analogue (5.0 g, 0.01704 mol) and anhydrous K₂CO₃ (4.71 g, 0.03408 mol) were added to 50 mL of N,N-dimethylformamide (DMF) and stirred at room temperature for 10 min. Then, epichlorohydrin (2.10 mL, 0.02556 mol) was added, and the mixture was stirred overnight. Afterward, 50 mL of ethyl acetate was added to the mixture, the organic layer was washed with saturated NH₄Cl solution, dried over anhydrous Na₂SO₄, and evaporated under vacuum. Column chromatography (CH₂Cl₂ / CH₃OH = 100:1, V / V) was used to give pure intermediate 1. It was a white solid, 82.28% yield.

[0060] Other epoxy intermediate compounds were synthesized using appropriate starting materials or substituents, following the steps in Example 1.

[0061] Example 2 Target compound N-(4-(3-(cyclopropylamino)-2-hydroxypropoxy)-3-methoxybenzyl)nonylamide

[0062] Intermediate 1 (0.2 g, 0.5720 mmol), cyclopropylamine (0.06535 g, 1.1400 mol), and isopropanol (6.0 mL) were added to a 15 mL pressure flask and stirred at 60 °C until intermediate 1 was completely reacted. The reaction mixture was extracted with water (20 mL), and the layers were separated by ethyl acetate (30 mL × 2). The organic layer was dried over anhydrous Na₂SO₄ and evaporated under vacuum. The target compound was separated and purified by column chromatography using CH₂Cl₂ and CH₃OH (10:1; V / V) as eluents. The final product was a white solid, target compound 1, in 54.15% yield.

[0063] Other target compounds were synthesized using appropriate starting materials or substituents, following the steps in Example 2.

[0064] The structures and 1H and 1C NMR spectra of the synthesized capsaicin compounds containing isopropanolamine are shown in Table 1, and their physicochemical properties are shown in Table 2.

[0065] Table 1 shows the 1H and 1C NMR spectra of some compounds.

[0066]

[0067]

[0068]

[0069]

[0070]

[0071]

[0072]

[0073]

[0074]

[0075]

[0076]

[0077]

[0078]

[0079]

[0080]

[0081]

[0082]

[0083]

[0084]

[0085]

[0086]

[0087]

[0088] Table 2 Physicochemical properties of the target compounds

[0089]

[0090]

[0091] Pharmacological Example 1

[0092] EC 50 Median effective concentration (MEC) is an important indicator for evaluating the sensitivity of plant pathogens to compounds, and it is also a crucial parameter for setting the compound concentration when studying the mechanism of action of target compounds. In concentration gradient experiments, five appropriate concentrations were set using the two-fold dilution method. Finally, the inhibition rate of the agent against the plant pathogen and the agent concentration were converted into logarithmic values, and the toxicity curve was obtained through regression analysis using SPSS software to calculate the EC50. 50 .

[0093] The effective medium concentration (EC) of the target compound against plant pathogens was determined using a turbidimetric method. 50The experimental subjects were *Xoo*, *Xac*, and *Xoc*, the pathogens of rice bacterial leaf blight. DMSO was dissolved in the culture medium as a blank control. *Xoo* (the pathogen of rice bacterial leaf blight was on M210 solid medium) was placed in NB medium and cultured in a constant temperature shaker at 28℃ and 180 rpm until the logarithmic growth phase. *Xoc* (the pathogen of rice bacterial leaf blight was on M210 solid medium) was placed in NB medium. *Xoc* (the pathogen of rice bacterial leaf blight was on M210 solid medium) was placed in NB medium and cultured in a constant temperature shaker at 28℃ and 180 rpm until the logarithmic growth phase. Prepare different concentrations (e.g., 100, 50, 25, 12.5, 6.25 μg / mL) of the drug (compound) in 5 mL of NB liquid culture medium containing the pathogen and add them to test tubes. Add 40 μL of NB liquid culture medium containing the plant pathogen bacteria to each tube. Incubate the tubes at 28-30℃ and 180 rpm in a constant temperature shaker. Culture the pathogens for rice bacterial blight, citrus canker, and rice bacterial leaf streak for 48 h. Measure the OD of each concentration of bacterial culture using a microplate reader. 595 The value was also measured, and the OD of the corresponding concentration of sterile NB liquid culture medium containing the toxin was also determined. 595 value.

[0094] Corrected OD value = OD value of sterile culture medium - OD value of sterile culture medium

[0095] Inhibition rate % = [(OD value of bacterial suspension in the corrected control medium - OD value of the corrected virus-containing medium) / OD value of bacterial suspension in the corrected control medium] × 100

[0096] The embodiments of this invention are provided to illustrate the technical solutions of this invention, but the content of the embodiments is not limited thereto. The experimental results of the target compound are shown in Table 3.

[0097] Table 3. EC50 of capsaicin compounds containing isopropanolamine against plant pathogenic bacteria. 50

[0098]

[0099]

[0100] As shown in Table 3, the target compounds exhibited good inhibitory activity against plant pathogens (such as *Bacillus oryzae*, *Citrus canker*, and *Bacillus streak*) in in vitro experiments. Compounds 26, 25, 19, and 18, in particular, showed exceptionally high activity against *Bacillus oryzae*, with EC50 values ​​exceeding 100%. 50 The concentrations ranged from 9.91 to 18.71 μg / mL; compounds 26, 18, and 16 exhibited extremely high activity against *Citrus canker*, the causal agent of citrus canker, with EC50 values ​​of 9.91–18.71 μg / mL. 50The concentration ranged from 7.04 to 15.40 μg / mL; compound 27 exhibited excellent inhibitory activity against *Bacillus streakus*, the causal agent of rice leaf streak, with an EC50 of 7.04–15.40 μg / mL. 50 The concentration was 22.00 μg / mL. Therefore, this type of compound shows great research potential and can be used to prepare pesticides against plant pathogenic bacteria.

[0101] Pharmacological Example 2: The in vitro antibacterial efficacy inhibition rate of compound 26 against plant pathogenic fungi was tested using the mycelial growth rate method.

[0102] The experimental subjects were *Gynostemma pentaphyllum*, *Rhizoctonia solani*, *Fusarium wilt*, *Sclerotinia sclerotiorum*, *Verticillium wilt*, and *Fusarium graminearum*. DMSO in sterile distilled water was used as a negative control, while cyazofamid was used as a positive control.

[0103] 2.1 Compound 26 was dissolved in DMSO (1.0 mL), then added to 9.0 mL of sterile water containing Tween 20 (1%), and then mixed with potato dextrose agar (PDA, 90.0 mL) to achieve a concentration of 25 mg / L for compound 26.

[0104] 2.2 Transfer the stock solution evenly into three petri dishes with a diameter of 9 cm.

[0105] 2.3 Then, cut a mycelial culture dish with a diameter of about 4 mm from the culture medium and aseptically inoculate it in the middle of a PDA plate.

[0106] 2.4 After inoculation, the plates were incubated at 27±1℃ for 3-5 days, with 3 replicates for each treatment condition.

[0107] 2.5 The radial growth of fungal colonies was measured, and the data were statistically analyzed. The antibacterial effect was calculated using the formula I = [(CT) / (C-0.4)] × 100%, where C is the diameter of fungal growth on the untreated PDA, T is the diameter of fungal growth on the treated PDA, and I is the inhibition rate.

[0108] The embodiments of this invention are provided to illustrate the technical solutions of this invention, but the content of the embodiments is not limited thereto. The experimental results of the target compound are shown in Table 4.

[0109] Table 4. In vitro antibacterial efficacy (%) of compound 26 against plant pathogenic fungi *Botrytis cinerea*, *Rhizoctonia solani*, *Fusarium wilt*, *Sclerotinia sclerotiorum*, *Verticillium wilt*, and *Fusarium graminearum*.

[0110]

[0111] As can be seen from Table 4, at 25 mg / L, compound 26 showed no activity against any of the six plant pathogenic fungi tested. However, according to literature reports, compounds containing capsaicin fragments have antifungal activity against plant pathogenic fungi. In the future, it may be considered to introduce other active fragments to improve the antifungal activity of this series of compounds and broaden their spectrum.

[0112] The above are merely preferred embodiments of this application, but the scope of protection of this application is not limited thereto. Any variations or substitutions that can be easily conceived by those skilled in the art within the scope of the technology disclosed in this application should be included within the scope of protection of this application. Therefore, the scope of protection of this application should be determined by the scope of the claims.

Claims

1. An isopropanolamine-containing capsaicinoid, characterized in that, selected from the group consisting of: , , , , , , , , , , , , , , , , , or .

2. A composition characterized in that, The active ingredient is the capsaicinoid compound containing isopropanolamine according to claim 1 or a stereoisomer thereof, or a salt thereof, or a solvate thereof.

3. Use of the isopropanolamine-containing capsaicinoid of claim 1 or the composition of claim 2 for controlling agricultural pests and diseases, characterized in that, The agricultural pest is Xanthomonas oryzae pv. oryzae, Xanthomonas axonopodis pv. citri and / or Xanthomonas oryzae pv. oryzicola.

4. A method for controlling agricultural pests and diseases, characterized by, The capsaicinoid compound containing isopropanolamine according to claim 1 or the composition according to claim 2 is allowed to act on the harmful organism or its living environment, and the agricultural pest is Xanthomonas oryzae pv. oryzae, Xanthomonas axonopodis pv. citri and / or Xanthomonas oryzae pv. oryzicola.

5. A method for protecting plants from agricultural pests, characterized in that, The capsaicinoid compound containing isopropanolamine according to claim 1 or the composition according to claim 2 is allowed to act on the plant or its living environment, and the agricultural pest is Xanthomonas oryzae pv. oryzae, Xanthomonas axonopodis pv. citri and / or Xanthomonas oryzae pv. oryzicola.

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