A carbonyl-containing coupling rigid fragment compound, a preparation method and a sterilization use

Abstract

The application discloses a kind of compounds with carbonyl coupling rigid fragment and its preparation method and bactericidal purposes.The compound has the structure shown in general formula I.A rigid carbonyl skeleton is constructed by connecting amino-containing 1,2,4-triazole through amide bond, and maleic acid structure and bioactive biological amine fragment are introduced, which are integrated in the same molecular skeleton by carbonyl coupling method.The compound synthesis route is short, the reaction condition is mild, and the yield is high.The biological activity test results show that the compound has broad-spectrum and significant inhibitory activity on rice sheath blight fungus, tomato botrytis cinerea, rice blast fungus, grape anthracnose fungus, oilseed rape sclerotinia sclerotiorum and many other plant pathogenic fungi.The compound has multi-target synergistic mechanism and low risk of drug resistance.

Description

Technical Field

[0001] This invention belongs to the field of pesticide chemistry and plant protection, specifically relating to a class of compounds with carbonyl-coupled rigid fragments, their preparation methods, and the application of such compounds in the preparation of fungicides. These compounds can serve as active skeletons for constructing lead compounds or candidate drugs with fungicidal activity. Furthermore, this invention also relates to fungicide compositions comprising these compounds and their application in the control of plant diseases. Background Technology

[0002] Diseases caused by plant pathogenic fungi pose a significant threat to global agricultural production and food security. Statistics show that the average annual yield loss of major food crops (such as rice, wheat, and corn) and cash crops (such as fruits and vegetables) due to fungal diseases exceeds 20%, and some outbreak diseases (such as wheat rust, rice blast, and gray mold) can even lead to total crop failure, causing serious economic losses.

[0003] Currently, chemical control remains the most important and effective means of controlling plant fungal diseases. Triazole fungicides exhibit broad-spectrum and highly effective control by inhibiting the biosynthesis of ergosterol in fungal cell membranes; representative varieties include tebuconazole, flutriafol, and propiconazole. However, long-term large-scale use has led to increasingly prominent resistance problems, and the relatively fixed molecular structures of these compounds limit further structural modification potential, making it difficult to meet the practical needs of resistance management.

[0004] To address these challenges, research in pesticide science has gradually shifted its focus to discovering fungicides with novel mechanisms of action and new molecular skeletons. Natural products and their structural derivatives have become important sources of lead compounds, among which biogenic amines with fungicidal activity have attracted significant attention. Studies have shown that biogenic amines are widely present in animals, plants, and microorganisms. Polyamine compounds such as putrescine, cadaverine, and spermidine exhibit inhibitory activity against various plant pathogenic fungi, and their mechanisms of action may involve interfering with the cell division cycle, inducing reactive oxygen species bursts, or binding to fungal DNA. However, natural biogenic amines generally suffer from rapid in vivo metabolism and limited activity, limiting their potential for direct application as pesticides. Therefore, optimization and modification using them as lead structures are necessary.

[0005] Furthermore, the maleic acid structure, due to its unique enediyl structure, endows the molecule with a certain degree of rigidity. Its two carbonyl groups can form multi-site hydrogen bond interactions with target proteins, enhancing binding affinity. The maleic acid structure can also be derivatized through various reaction pathways such as ring opening, ring closing, esterification, and amidation, and can be used to construct a diverse library of compounds. The amide structure is also a key functional group in many antibacterial and anticancer drugs; some compounds containing amide structures can disrupt the integrity of pathogenic bacterial cell membranes or inhibit the activity of key enzymes.

[0006] Although the aforementioned active fragments have shown significant value in medicinal chemistry, there are no reports of research on constructing rigid molecular skeletons using carbonyl coupling and systematically applying them to the design of agricultural fungicides. Current technology lacks a technical approach to integrate 1,2,4-triazole, maleic acid structures, and biogenic amine fragments into the same molecular skeleton via carbonyl coupling, and there are also no studies on the application of such compounds in the control of plant pathogenic fungi.

[0007] This invention aims to provide a novel class of compounds with rigid carbonyl coupling fragments and their synthetic methods to overcome the resistance problem caused by long-term use of existing triazole fungicides. Specifically, this invention constructs a class of novel compounds with rigid carbonyl skeletons through an active substructure splicing strategy, which can be used to develop fungicide lead compounds or candidate drugs with novel mechanisms of action and broad-spectrum antibacterial activity. Summary of the Invention

[0008] To achieve the above objectives, the present invention adopts the following technical solution: 1. The object of this invention is to provide a compound having a carbonyl-coupled rigid segment. The compound is characterized in that it has the structure shown in general formula I: I in: R is selected from one of putrescine, histamine, cystamine, tryptamine, cadaverine, or spermine; Ar is selected from one of the following groups: .

[0009] 2. A further objective of this invention is to provide a method for preparing the compound having a carbonyl coupling rigid fragment, characterized by comprising the following steps: (1) Dissolve carboxylic acid compound II and 3-amino-1,2,4-triazole in organic solvent A, add alkali and condensing agent, stir at room temperature for 3 to 6 hours to carry out the reaction, and after the reaction is completed, separate and purify the solution to obtain intermediate III; (2) Dissolve intermediate III and maleic anhydride in organic solvent B, add alkali, and stir at 50°C for 8 to 16 hours to carry out the reaction. After the reaction is completed, wash and dry, then extract with organic solvent C and purify by column chromatography to obtain α,β-unsaturated carboxylic acid compound with carbonyl coupling rigid fragment, denoted as compound IV. (3) Compound IV and biogenic amine V were dissolved in organic solvent D, and alkali and condensing agent were added. The mixture was stirred at room temperature for 3 to 6 hours to carry out the reaction. After the reaction was completed, the mixture was washed, dried, extracted with organic solvent E, and purified by column chromatography to obtain α,β-unsaturated amide compound I with a carbonyl coupling rigid fragment.

[0010] Its synthetic route is as follows:

[0011] in: Organic solvent A is dichloromethane; Organic solvent B is methanol; Organic solvent C is selected from any one of dichloromethane, ethyl acetate, methanol, and n-hexane; Organic solvent D is selected from any one of acetonitrile, dichloromethane, tetrahydrofuran, N,N-dimethylformamide, dimethyl sulfoxide, and 1,4-dioxane; Organic solvent E is selected from any one of dichloromethane, ethyl acetate, methanol, and n-hexane; The base is selected from triethylamine, N 1,8-ethyldiisopropylamine, lithium hydroxide, potassium phosphate, potassium carbonate, potassium tert-butoxide, pyridine, cesium carbonate, cesium fluoride, 1,8-diazabicyclo[5.4.0]undec-7-ene, 1,5-diazabicyclo[4.3.0]non-5-ene; The condensing agent is selected from any one of 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride, N,N'-carbonyldiimidazole, 2-(7-azabenzotriazole)-N,N,N',N'-tetramethylurea hexafluorophosphate, 1-hydroxybenzotriazole, and N,N,N',N'-tetramethylchloroformamidine hexafluorophosphate. The developing solvent used in column chromatography is selected from any two of methanol, ethyl acetate, dichloromethane, and n-hexane, wherein the volume ratio of n-hexane to ethyl acetate is (1-5):1; or the volume ratio of dichloromethane to methanol is (10-40):1.

[0012] 3. A further objective of this invention is to provide a preferred technical solution for the preparation method of the compound having a carbonyl coupling rigid fragment: In step (1), the molar ratio of compound II to 3-amino-1,2,4-triazole is 1:1.5; In step (1), the molar ratio of compound II to 2-(7-azabenzotriazole)-N,N,N',N'-tetramethylurea hexafluorophosphate is 1:1.5; In step (1), the molar ratio of compound II to triethylamine is 1:1.3; In step (1), the millimolecular volume ratio of compound II to organic solvent A is 1 mmol: 2 mL.

[0013] In step (2), the molar ratio of intermediate III to maleic anhydride is 1:1.2.

[0014] In step (2), the millimolecular volume ratio of intermediate III to organic solvent B is 1 mmol: 5 mL.

[0015] In step (3), the molar ratio of compound IV to biogenic amine V is 1:2.

[0016] In step (3), the molar ratio of compound IV to 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride is 1:1.5.

[0017] In step (3), the molar ratio of compound IV to triethylamine is 1:1.3.

[0018] In step (3), the millimolecular volume ratio of compound IV to organic solvent D is 1 mmol: 10 mL.

[0019] 4. The present invention also provides a fungicide composition, characterized in that it comprises an effective amount of the compound of claim 1 and a pesticide-acceptable carrier, excipient or adjuvant.

[0020] 5. The present invention further provides the application of the compound or the fungicide composition in the prevention and control of plant diseases, characterized in that the plant diseases are caused by plant pathogenic fungi, and preferably, it is used to prevent and control one or more of rice sheath blight fungus, tomato gray mold fungus, rice blast fungus, grape anthracnose fungus, rapeseed sclerotinia sclerotinia and Fusarium graminearum.

[0021] Compared with the prior art, the present invention has the following beneficial effects: (1) Novel structure, enhanced rigidity of the skeleton This invention is the first to integrate a 1,2,4-triazole pharmacophore, a rigid aromatic backbone, a maleic acid structural unit, and a biogenic amine active fragment into a single molecular backbone via carbonyl coupling. This rigid backbone facilitates stable multi-site interactions with target proteins, improving binding affinity and selectivity.

[0022] (2) The synthesis method is simple and efficient. The present invention has a short synthetic route, readily available raw materials, mild reaction conditions (room temperature to 50°C), simple operation, high yield, and is suitable for large-scale production, with good industrialization prospects.

[0023] (3) Broad-spectrum bactericidal activity Bioactivity tests showed that the compounds of this invention exhibited significant inhibitory activity against a variety of important plant pathogenic fungi, including rice sheath blight, tomato gray mold, rice blast fungus, grape anthracnose fungus, rapeseed sclerotinia, and Fusarium graminearum. Some compounds showed better activity than existing commercially available fungicides, were safe for crops without causing phytotoxicity, and have the potential to be developed as broad-spectrum fungicides.

[0024] (4) Multi-target synergistic mechanism, low risk of drug resistance The compounds of this invention may exert their fungicidal effect through a multi-target synergistic mechanism: the 1,2,4-triazole unit competitively inhibits the activity of fungal CYP51 enzymes, blocking ergosterol biosynthesis; the maleic acid structural unit embeds into the ubiquinone binding site of succinate dehydrogenase, interfering with mitochondrial respiration and energy metabolism, while its α,β-unsaturated carbonyl group can act as a Michael receptor to induce the accumulation of reactive oxygen species; the biogenic amine fragment alters cell membrane permeability through electrostatic interactions and interferes with polyamine metabolic balance; the rigid skeleton optimizes the molecular spatial conformation, enhancing the binding affinity of each pharmacophore to its target. Furthermore, some compounds can induce systemic resistance in plants. This multi-target action characteristic makes it difficult for pathogens to develop resistance through single-gene mutations, and there is no cross-resistance with existing triazole, SDHI, and QoI fungicides, demonstrating low resistance risk and good application potential. Attached Figure Description

[0026] Figure 1 This is a schematic diagram of the structure of the compound of general formula I of the present invention.

[0027] Figure 2 This is a schematic diagram of the synthesis route of the present invention. Detailed Implementation

[0029] To enable those skilled in the art to better understand the present invention, the present invention will now be further described in conjunction with specific embodiments, but the scope of protection of the present invention is not limited thereto.

[0030] All pharmaceuticals involved in this invention are commercially available and have not undergone any processing.

[0031] Example 1: N 1 -(2-(1H-imidazol-4-yl)ethyl)- N 4 Preparation of -(1-(2,4-dimethylthiazol-5-carbonyl)-1H-1,2,4-triazol-3-yl)fumaramide (I-1)

[0032] 1.1 Synthesis of intermediate formula III Carboxylic acid compound II (10.0 mmol) and 3-amino-1,2,4-triazole (15.0 mmol) were placed in a 100 mL round-bottom flask, and 20 mL of dichloromethane was added. The mixture was stirred until completely dissolved. Then, N-ethyldiisopropylamine (2.6 mL, 15.0 mmol) was added as a base, and 2-(7-benzotriazole oxide)-N,N,N',N'-tetramethylurea hexafluorophosphate (15.0 mmol) was added as a condensing agent. The reaction mixture was stirred at room temperature (25 °C) for 4 hours, and the reaction progress was monitored by thin-layer chromatography (TLC, developing solvent: dichloromethane / methanol = 10 / 1, v / v) until carboxylic acid compound II was completely converted. After the reaction was complete, the reaction mixture was slowly poured into 100 mL of ice water, and a solid precipitated. The solid was extracted with ethyl acetate (3 × 50 mL), and the organic phases were combined. The organic phase was washed sequentially with saturated brine (50 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to remove the solvent. The crude product was purified by silica gel column chromatography (eluent: dichloromethane / methanol = 30 / 1, v / v) to give a white solid intermediate of formula III in 92.5% yield.

[0033] The intermediate III (5.0 mmol) synthesized in the previous step was dissolved in 20 mL of methanol, and maleic anhydride (6.0 mmol) was added. After stirring and dissolving, anhydrous sodium acetate (0.41 g, 5.0 mmol) was added as a base. The reaction system was heated to 50 °C and stirred continuously for 12 hours. During the reaction, the solution gradually changed from colorless to pale yellow. TLC monitoring (developing solvent: dichloromethane / methanol = 5 / 1, v / v) showed that intermediate III was completely consumed, and the reaction was stopped. The reaction solution was cooled to room temperature, and most of the solvent was removed by vacuum distillation, giving a yellow viscous residue. 50 mL of dichloromethane was added to the residue, and the mixture was washed successively with distilled water (2 × 30 mL) and saturated brine (30 mL). The organic phase was collected and dried over anhydrous sodium sulfate. After filtration and concentration of the filtrate under reduced pressure, it was purified by silica gel column chromatography (eluent: dichloromethane / methanol = 10 / 1, v / v) to obtain a pale yellow solid α,β-unsaturated carboxylic acid compound with a carbonyl coupling rigid fragment, namely compound IV, with a yield of 81.3%.

[0034] Compound IV (3.0 mmol) and histamine (6.0 mmol) were placed in a 50 mL round-bottom flask, and 30 mL of anhydrous dichloromethane was added as organic solvent D. The mixture was stirred to dissolve. The mixture was cooled to 0 °C in an ice bath, and 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (4.5 mmol), 1-hydroxybenzotriazole (4.5 mmol), and triethylamine (3.9 mmol) were added sequentially. The ice bath was removed, and the reaction mixture was allowed to rise naturally to room temperature. The reaction was stirred for 5 hours. TLC monitoring (developing solvent: dichloromethane / methanol = 5 / 1, v / v) showed that the reaction was complete. After the reaction was complete, the reaction solution was diluted with 30 mL of dichloromethane. The organic phase was washed sequentially with saturated citric acid solution (2 × 20 mL), saturated sodium bicarbonate solution (2 × 20 mL), and saturated brine (20 mL). The organic phase was collected, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (eluent: dichloromethane / methanol = 15 / 1, v / v) to give the target product I-1 as a white to off-white solid with a yield of 78.8%.

[0035] Examples 2-66: Preparation of compounds I-2 to I-66 Following the synthetic method of Example 1, only the carboxylic acid compound II (with different Ar groups) in step 1.1 and the biogenic amine V (with different R groups) in step 1.3 were replaced according to Table 1 to obtain compounds I-2 to I-66. The yields and physicochemical data of each compound are summarized in Table 1.

[0036] Table 1. Physicochemical data of compounds with carbonyl coupling rigid segments I-1 2,4-Dimethylthiazolyl-5-yl histamine group White solid 78.8 I-2 2,4-Dimethylthiazolyl-5-yl Cadani White solid 61.2 I-3 2,4-Dimethylthiazolyl-5-yl putrescine White solid 74.5 I-4 2,4-Dimethylthiazolyl-5-yl Cystamine White solid 88.9 I-5 2,4-Dimethylthiazolyl-5-yl Spermine White solid 83.3 I-6 2,4-Dimethylthiazolyl-5-yl tryptophan White solid 67.8 I-7 Thiazol-4-yl histamine group White solid 72.1 I-8 Thiazol-4-yl Cadani White solid 81.6 I-9 Thiazol-4-yl putrescine White solid 83.4 I-10 Thiazol-4-yl Cystamine White solid 78.2 I-11 Thiazol-4-yl Spermine White solid 69.7 I-12 Thiazol-4-yl tryptophan White solid 86.5 I-13 1-Methyl-3-(difluoromethyl)-1H-pyrazole-4-yl histamine group White solid 71.3 I-14 1-Methyl-3-(difluoromethyl)-1H-pyrazole-4-yl Cadani White solid 64.9 I-15 1-Methyl-3-(difluoromethyl)-1H-pyrazole-4-yl putrescine White solid 82.1 I-16 1-Methyl-3-(difluoromethyl)-1H-pyrazole-4-yl Cystamine White solid 76.4 I-17 1-Methyl-3-(difluoromethyl)-1H-pyrazole-4-yl Spermine White solid 80.7 I-18 1-Methyl-3-(difluoromethyl)-1H-pyrazole-4-yl tryptophan White solid 83.2 I-19 1-Methyl-3-(trifluoromethyl)-1H-pyrazole-4-yl histamine group White solid 70.0 I-20 1-Methyl-3-(trifluoromethyl)-1H-pyrazole-4-yl Cadani White solid 84.6 I-21 1-Methyl-3-(trifluoromethyl)-1H-pyrazole-4-yl putrescine White solid 77.8 I-22 1-Methyl-3-(trifluoromethyl)-1H-pyrazole-4-yl Cystamine White solid 63.5 I-23 1-Methyl-3-(trifluoromethyl)-1H-pyrazole-4-yl Spermine White solid 89.0 I-24 1-Methyl-3-(trifluoromethyl)-1H-pyrazole-4-yl tryptophan White solid 75.1 I-25 1H-pyrazole-4-yl histamine group White solid 87.4 I-26 1H-pyrazole-4-yl Cadani White solid 68.3 I-27 1H-pyrazole-4-yl putrescine White solid 82.6 I-28 1H-pyrazole-4-yl Cystamine White solid 90.5 I-29 1H-pyrazole-4-yl Spermine White solid 73.9 I-30 1H-pyrazole-4-yl tryptophan White solid 66.7 I-31 1H-imidazol-4-yl histamine group White solid 85.2 I-32 1H-imidazol-4-yl Cadani White solid 79.4 I-33 1H-imidazol-4-yl putrescine White solid 62.8 I-34 1H-imidazol-4-yl Cystamine White solid 91.7 I-35 1H-imidazol-4-yl Spermine White solid 74.3 I-36 1H-imidazol-4-yl tryptophan White solid 87.6 I-37 1-Methylpiperidin-4-yl histamine group White solid 69.2 I-38 1-Methylpiperidin-4-yl Cadani White solid 81.5 I-39 1-Methylpiperidin-4-yl putrescine White solid 84.8 I-40 1-Methylpiperidin-4-yl Cystamine White solid 76.9 I-41 1-Methylpiperidin-4-yl Spermine White solid 65.1 I-42 1-Methylpiperidin-4-yl tryptophan White solid 88.2 I-43 Azacyclobutane-3-yl histamine group White solid 72.8 I-44 Azacyclobutane-3-yl Cadani White solid 88.4 I-45 Azacyclobutane-3-yl putrescine White solid 80.1 I-46 Azacyclobutane-3-yl Cystamine White solid 67.3 I-47 Azacyclobutane-3-yl Spermine White solid 85.9 I-48 Azacyclobutane-3-yl tryptophan White solid 70.6 I-49 2-Methoxypyridine-3-yl histamine group White solid 83.7 I-50 2-Methoxypyridine-3-yl Cadani White solid 77.2 I-51 2-Methoxypyridine-3-yl putrescine White solid 64.4 I-52 2-Methoxypyridine-3-yl Cystamine White solid 82.5 I-53 2-Methoxypyridine-3-yl Spermine White solid 79.8 I-54 2-Methoxypyridine-3-yl tryptophan White solid 86.1 I-55 2-Mercaptopyridine-3-yl histamine group White solid 73.2 I-56 2-Mercaptopyridine-3-yl Cadani White solid 68.9 I-57 2-Mercaptopyridine-3-yl putrescine White solid 86.3 I-58 2-Mercaptopyridine-3-yl Cystamine White solid 75.5 I-59 2-Mercaptopyridine-3-yl Spermine White solid 81.9 I-60 2-Mercaptopyridine-3-yl tryptophan White solid 89.7 I-61 2,3-Dihydro-1H-ind-2-yl histamine group White solid 71.8 I-62 2,3-Dihydro-1H-ind-2-yl Cadani White solid 84.0 I-63 2,3-Dihydro-1H-ind-2-yl putrescine White solid 78.5 I-64 2,3-Dihydro-1H-ind-2-yl Cystamine White solid 83.7 I-65 2,3-Dihydro-1H-ind-2-yl Spermine White solid 66.2 I-66 2,3-Dihydro-1H-ind-2-yl tryptophan White solid 90.0 .

[0037] Example 67: Test of bactericidal activity of the target compound (1) Test pathogens The following eight plant pathogenic fungi were selected as test targets: Rice sheath blight fungus ( Rhizoctonia solani ), tomato gray mold ( Botrytis cinerea Rice blast fungus ( Pyricularia oryzae Grape anthracnose bacteria ( Colletotrichum gloeosporioides ), rapeseed sclerotinia pathogen ( Sclerotinia sclerotiorum Fusarium graminearum ( ), Fusarium graminearum ( Fusarium graminearum ), wheat black smut fungus ( Ustilago tritici ) and cucumber wilt pathogen ( Fusarium oxysporum f. sp. cucumerinum ).

[0038] (2) Test methods The in vitro antibacterial activity of the test compounds was determined using the mycelial growth rate method. Each test compound was dissolved in dimethyl sulfoxide (DMSO) to prepare a solution with a concentration of 2.0 × 10⁻⁶.4 The stock solution was prepared at a concentration of 50 μg / mL. The antibacterial activity of the test compound against the above 8 pathogens was determined at a final concentration of 50 μg / mL. Sterile water treatment was used as a blank control, and tetraconazole was used as a positive control. Each treatment was repeated in 3 replicates.

[0039] Specific procedures: Under aseptic conditions, take 50 μL of the stock solution of the test compound and add it to sterilized potato dextrose agar (PDA) medium cooled to approximately 50°C (total volume 20 mL). After thorough shaking and mixing, pour the mixture into sterile petri dishes to prepare a plate with a final concentration of 50 μg / mL. Cut a 5 mm diameter mycelial disc from the edge of the pre-cultured pathogen colony and inoculate it in the center of the petri dish. Incubate the inoculated petri dishes in the dark at 27°C for 72 h. Measure the diameter of each treatment colony using the cross-sectional method, repeating the measurement twice for each colony and taking the average value. The inhibition rate is calculated using the following formula: Inhibition rate (%) = [(Control colony diameter - Treated colony diameter) / (Control colony diameter - 5 mm)] × 100% (3) Experimental results The activity test results are shown in Table 2. The compounds with carbonyl-coupled rigid fragments described in this invention exhibited varying degrees of inhibitory activity against the eight tested plant pathogenic fungi at a concentration of 50 μg / mL. Among them, compounds such as I-12, I-18, I-30, I-35, I-36, I-59, I-60, and I-66 showed excellent inhibitory effects against the tested pathogens (inhibition rate > 80%), and some compounds showed better activity than the control agent flufenoxuron. This indicates that the compounds of this invention have broad-spectrum fungicidal activity and can be further developed as lead compounds for novel fungicides.

[0040] Table 2. Bactericidal activity of compounds with carbonyl-coupled rigid fragments (inhibition rate, in %, 50 μg / mL) I-1 60.3 60.23 60.37 60.00 60.24 60.42 60.38 60.25 60.16 I-2 66.8 66.2 66.4 65.1 65.8 66.2 66.8 67.9 67.8 I-3 73.4 72.1 72.6 70.0 71.3 71.9 73.3 74.6 75.5 I-4 80.1 78.3 78.6 75.3 76.9 77.7 79.7 81.3 83.1 I-5 86.7 84.2 84.8 80.4 82.4 83.5 86.2 87.9 90.8 I-6 93.2 90.1 90.2 85.5 87.9 89.2 92.6 94.6 90.2 I-7 61.4 61.5 61.5 60.5 61.5 61.6 61.5 61.4 61.3 I-8 67.9 67.3 67.7 65.1 66.9 67.3 67.9 69.1 68.9 I-9 74.6 73.2 73.1 70.2 72.4 73.1 74.4 75.7 76.6 I-10 81.2 79.2 79.9 75.5 77.9 78.8 80.8 82.4 84.3 I-11 87.7 85.3 85.4 80.4 83.5 84.6 87.3 89.1 91.9 I-12 94.3 91.4 91.7 85.5 89.1 90.4 93.7 95.7 92.4 I-13 62.4 62.8 62.8 61.0 62.6 62.7 62.5 62.5 70.1 I-14 69.0 68.4 68.2 66.1 68.0 68.5 68.9 70.2 77.7 I-15 75.6 74.6 74.5 71.2 73.5 74.3 75.4 76.8 85.4 I-16 82.4 80.3 80.9 76.0 79. 8 80.1 81.9 83.5 93. 6 I-17 88.7 86.4 86.6 81.4 84.6 85.8 88.3 90.2 93.5 I-18 95.3 92.2 92.3 86.1 90.2 91.5 94.8 90.1 91.2 I-19 63.51 63.1 63.9 61.5 63.7 63. 8 63.6 63.6 68.8 I-20 70.08 69.5 69.4 66.6 69.1 69.6 70.4 71.3 76.5 I-21 76.6 75.4 75.7 71.5 74.7 75.4 76.5 77.9 74.2 I-22 83.2 81.3 81.3 76.5 80.2 81.2 82.9 84.6 84.7 I-23 89.9 87.5 87.6 81.4 85.3 86.9 89.4 91.3 92.3 I-24 90.2 93.3 93.1 86.6 91.7 92.7 95.0 94.8 90.0 I-25 64.6 64.4 64.9 62.0 64. 8 64.3 64.7 72.4 67.6 I-26 71.2 70.6 70.5 67.1 70.2 70.9 71.1 79.1 75.3 I-27 77.7 76.5 76.8 72.4 75.7 76.6 77.6 85.8 75.7 I-28 84.3 82.5 82.4 77.3 81.3 82.3 84.0 87.4 73.4 I-29 90.8 88.6 88.7 82.2 86.8 88.1 90.5 90.1 81.3 I-30 91.6 94.4 94.3 87.5 92.4 93.8 90.1 91.9 88.7 I-31 65.7 65.7 60.1 62.8 60.9 65.2 65.7 73.6 60.1 I-32 72.2 71.8 71.5 67.5 71.3 71.9 72.2 70.2 66.8 I-33 78.8 77.7 77.9 72.2 76.8 77.7 78.6 76.9 74.5 I-34 85.4 83.6 83.4 77.7 82.4 83.4 85.8 83.6 82.2 I-35 91.9 89.7 89.9 82.4 87.5 89.2 91.5 91.3 89.8 I-36 92.3 95.0 95.5 87.6 93.6 94.9 91.9 88.9 91.7 I-37 68.9 60.6 61.2 63.0 61.9 60.3 68.7 75.6 68.8 I-38 75.5 66.9 66.7 68.1 66.4 66.1 74.8 72.2 76.5 I-39 82.1 72.8 72.2 73.0 71.8 71.8 81.3 78.9 84.2 I-40 78.6 78.7 78.6 78.3 77.5 77.6 87.7 85.6 81.8 I-41 95.2 84.8 85.1 83.4 83.6 83.4 84.2 92.4 87.3 I-42 93.4 90.6 91.6 88.7 88.0 89.1 82.1 80.7 89.9 I-43 69.9 61.9 62.3 63.5 62.1 61.5 69.5 66.4 74.6 I-44 66.6 67.3 67.8 68.1 67.5 67.3 75.9 73.1 75.8 I-45 73.3 73.8 74.2 73.5 73.9 73.1 82.4 70.8 82.4 I-46 79.7 79.7 79.8 78.3 78.6 78.8 88.8 80.3 83.3 I-47 80.7 85.9 86.3 83.5 84.2 84.5 80.2 83.3 81.1 I-48 84.5 91.7 92.7 88.6 89.7 90.3 85.8 91.2 88.7 I-49 71.1 62.3 63.4 64.0 63.1 62.7 72.4 77.8 76.4 I-50 77.6 68.1 68.9 69.1 68.6 68.4 78.7 74.5 74.7 I-51 80.2 74.9 75.3 74.0 74.2 74.2 75.1 81.2 74.6 I-52 84.8 80.8 80.8 79.3 79.4 79.9 81.6 84.7 82.2 I-53 81.4 86.9 87.4 84.4 85.8 85.7 83.3 82.3 79.8 I-54 85.6 92.8 93.8 89.6 90.2 91.5 89.7 89.0 87.5 I-55 72.2 63.7 64.6 64.0 64.3 63.8 76.2 75.7 75.2 I-56 78.7 69.3 70.0 69.5 69.7 69.6 82.6 82.3 75.6 I-57 75.3 75.1 76.5 74.2 75.3 75.3 79.1 80.4 73.4 I-58 81.8 81.9 81.6 79.5 80.9 81.1 84.5 85.8 81.1 I-59 92.4 87.0 88.4 84.4 86.4 86.8 84.3 83.5 88.7 I-60 96.7 93.9 94.9 89.8 91.9 92.6 90.8 90.3 90.9 I-61 73.2 64.2 65.7 65.0 60.3 64.9 67.2 66.8 60.2 I-62 75.8 70.8 71.2 70.0 70.8 70.7 73.6 73.7 67.8 I-63 76.3 76.2 77.6 75.2 76.2 76.5 80.3 80.3 75.5 I-64 82.9 83.1 83.7 80.3 81.6 82.2 75.8 77.9 83.4 I-65 90.3 88.1 89.5 85.0 87.5 88.0 80.4 84.6 90.8 I-66 96.8 94.9 95.1 90.5 93.4 93.7 86.8 91.3 90.2 Fluoroether 57.8 87.9 99.7 61.5 74.2 63.5 83.6 71.6 58.8 .

[0041] The contents described in this specification are merely an enumeration of the implementation forms of the inventive concept. The scope of protection of this invention should not be regarded as limited to the specific forms described in the embodiments. The scope of protection of this invention is also limited to the equivalent technical means that can be conceived by those skilled in the art based on the inventive concept.

Claims

1. A compound having a carbonyl-coupled rigid segment, characterized in that, The compound has the structure shown in general formula I: I in: R is selected from one of putrescine, histamine, cystamine, tryptamine, cadaverine, or spermine; Ar is selected from one of the following groups: 。 2. The compound according to claim 1, characterized in that, The compound is specifically any one of the following: Markushton formulas (I-1 to I-66): Ar-carbonyl-1H-1,2,4-triazol-3-yl- N -Fumaroyl-R; Ar: 2,4-Dimethylthiazol-5-yl, thiazol-5-yl, 3-difluoromethyl-1-methyl-1H-pyrazole-4-yl, 1-methyl-3-trifluoromethyl-1H-pyrazole-4-yl, 1H-pyrazole-4-yl, 1H-imidazol-4-yl, 1-methylpiperidin-4-yl, azacyclobutane-3-yl, 2-methoxypyridin-3-yl, pyridin-2-thiol-3-yl, 1H-indole-2-yl; R: putrescine, histamine, cystamine, tryptamine, cadaverine, spermine.

3. A method for preparing a compound with a carbonyl coupling rigid segment as described in claim 1 or 2, characterized in that, Includes the following steps: (1) Dissolve carboxylic acid compound II and 3-amino-1,2,4-triazole in organic solvent A, add alkali and condensing agent, stir at room temperature for 3 to 6 hours to carry out the reaction, separate and purify after the reaction is completed to obtain intermediate III; (2) Dissolve intermediate III and maleic anhydride in organic solvent B, add alkali, and stir at 50°C for 8 to 16 hours to carry out the reaction. After the reaction is completed, wash, dry, extract and purify by column chromatography to obtain compound IV. (3) Compound IV and biogenic amine V were dissolved in organic solvent D, and alkali and condensing agent were added. The mixture was stirred at room temperature for 3 to 6 hours to carry out the reaction. After the reaction was completed, the mixture was washed, dried, extracted and purified by column chromatography to obtain compound I. in: Organic solvent A is dichloromethane; Organic solvent B is methanol; Organic solvent D is selected from any one of acetonitrile, dichloromethane, tetrahydrofuran, N,N-dimethylformamide, dimethyl sulfoxide, and 1,4-dioxane; The base is selected from any one of triethylamine, N-ethyldiisopropylamine, lithium hydroxide, potassium phosphate, potassium carbonate, potassium tert-butoxide, pyridine, cesium carbonate, cesium fluoride, 1,8-diazabicyclo[5.4.0]undec-7-ene, and 1,5-diazabicyclo[4.3.0]non-5-ene; The condensing agent is selected from any one of 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride, N,N'-carbonyldiimidazole, 2-(7-azabenzotriazole)-N,N,N',N'-tetramethylurea hexafluorophosphate, 1-hydroxybenzotriazole, and N,N,N',N'-tetramethylchloroformamidine hexafluorophosphate.

4. The preparation method according to claim 3, characterized in that: In step (1), the molar ratio of compound II to 3-amino-1,2,4-triazole is 1:1.5; In step (2), the molar ratio of intermediate III to maleic anhydride is 1:1.2; In step (3), the molar ratio of compound IV to biogenic amine V is 1:

2.

5. A bactericide composition, characterized in that, It contains an effective amount of the compound of claim 1 or 2, as well as a pesticide-acceptable carrier, excipient, or adjuvant.

6. The bactericide composition according to claim 5, characterized in that, The composition is in the form of a wettable powder, emulsifiable concentrate, suspension concentrate, water-dispersible granules, or microemulsion.

7. The use of the compound of claim 1 or 2 or the fungicide composition of claim 5 in the control of plant diseases, characterized in that, The plant disease is caused by plant pathogenic fungi.

8. The application according to claim 7, characterized in that, The plant pathogenic fungus is selected from *Rhizoctonia solani* (rice sheath blight fungus). Rhizoctonia solani ), tomato gray mold ( Botrytis cinerea ), rice blast fungus ( Firefly rice Grape anthracnose bacteria ( Colletotrichum gloeosporioides ), rapeseed sclerotinia pathogen ( Sclerotinia sclerotia Fusarium graminearum ( ), Fusarium graminearum ( Fusarium gramineae ), wheat black smut fungus ( Wheat blight ) and cucumber wilt pathogen ( Fusarium oxysporum f. sp. cucumerinum One or more of the following.

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