4-aryl naphthoimidazole compound as well as preparation method and application thereof

Abstract

The invention belongs to the field of chemical synthesis, and particularly relates to a 4-aryl naphthoimidazole compound as well as a preparation method and application thereof. The chemical structural formula of the 4-aryl naphthoimidazole compound is as shown in formula I. The 4-aryl naphthoimidazole compound is easy to synthesize and has extremely high inhibitory activity on fungi such as apple anthracnose pathogenic bacteria, apple ring rot pathogenic bacteria, rice blast pathogenic bacteria, cabbage black spot pathogenic bacteria and / or corn curvularia pathogenic bacteria; the effect is obviously better than that of the currently common clinically applied antifungal drug azoxystrobin. The preparation method disclosed by the invention has the advantages of short synthesis route, simple and easily available raw materials, simple post-treatment and the like, and is suitable for industrial large-scale production. # imgabs0 #

Description

Technical Field

[0001] The present invention belongs to the field of chemical synthesis, and in particular relates to a 4-aryl naphthoimidazole compound and a preparation method and application thereof. Background Art

[0002] Fungal diseases are a key factor in plant diseases, causing severe negative impacts on crop growth, often leading to significant reductions in yield and quality. Chemical fungicides currently dominate control strategies. However, the long-term and extensive use of chemical fungicides not only leaves harmful residues in crops, impacting the safety and quality of agricultural products, but also encourages pathogens to develop resistance, gradually weakening control effectiveness. Furthermore, chemical fungicides can cause significant damage to the ecological environment, such as contaminating soil and water bodies and harming beneficial organisms.

[0003] In view of this, the development of new anti-plant pathogen drugs that are highly effective, low-toxic and environmentally friendly has become an important issue that needs to be urgently addressed in the agricultural field. This is of great significance for ensuring the healthy growth of crops, achieving sustainable agricultural development and protecting the ecological environment.

[0004] Therefore, based on this, the technical solution of the present invention is proposed. Summary of the Invention

[0005] In order to solve the problems existing in the prior art, the present invention provides a 4-aryl naphthoimidazole compound, the chemical structure of which is shown in Formula I:

[0006]

[0007] Wherein, R is methyl, ethyl, isopropyl or chlorine.

[0008] Based on the same technical concept, the present invention further provides a method for preparing the 4-aryl naphthoimidazole compound, which comprises the following steps:

[0009] (1) Under an inert gas atmosphere, 4,5-diiodo-1-methyl-1H-imidazole is dissolved in anhydrous tetrahydrofuran, and C2H5MgBr is added after dissolution, and then stirred under heating conditions to react to obtain a first reaction solution;

[0010] (2) adding benzaldehyde to the first reaction solution, maintaining the temperature and continuing to stir the reaction to obtain a second reaction solution;

[0011] (3) quenching the second reaction solution, separating the liquid, collecting the organic phase, washing, drying, concentrating, and filtering to obtain an intermediate;

[0012] (4) dissolving the intermediate in anhydrous tetrahydrofuran, adding C2H5MgBr, and stirring under heating conditions to react to obtain a third reaction solution;

[0013] (5) adding substituted benzaldehyde to the third reaction solution to continue the reaction, removing the Grignard reagent after completion, then adding dichloromethane and HBr to carry out cyclization, and finally purifying to obtain the corresponding 4-aryl naphthoimidazole compound.

[0014] The synthetic route of the present invention is shown in Formula II.

[0015]

[0016] Preferably, in step (1):

[0017] The inert gas atmosphere is a nitrogen atmosphere;

[0018] And / or, the heating temperature is 20-30° C., and the reaction time is 2-3 hours.

[0019] Preferably, in step (2), the reaction temperature is 20-30° C., and the reaction time is 20-24 h.

[0020] Preferably, in step (3), the second reaction liquid is quenched with a saturated aqueous ammonium chloride solution, and then separated by a separatory funnel and the organic phase is collected; the aqueous phase is extracted with ethyl acetate, and the combined organic phases are washed with saturated brine, dried over anhydrous Na2SO4, and concentrated; the residue is washed with ethyl acetate and filtered to obtain an intermediate.

[0021] Preferably, in step (4), the heating temperature is 20-30° C., and the reaction time is 3-4 h.

[0022] Preferably, in step (5):

[0023] The substituted benzaldehyde is methyl substituted benzaldehyde, ethyl substituted benzaldehyde, isopropyl substituted benzaldehyde or chlorine substituted benzaldehyde;

[0024] And / or, the reaction temperature is 20-30° C., and the reaction time is 20-24 h;

[0025] And / or, the ring closing temperature is 20-30° C., and the ring closing time is 12-14 hours.

[0026] Based on the same technical concept, the present invention further provides a use of the 4-aryl naphthoimidazole compound in the preparation of antifungal drugs.

[0027] Preferably, the fungus is apple anthracnose pathogen, apple ring rot pathogen, rice blast pathogen, cabbage black spot pathogen and / or corn Curvularia serrata pathogen.

[0028] Based on the same technical concept, the present invention further provides an antifungal drug, which comprises the 4-aryl naphthoimidazole compound.

[0029] The beneficial effects of the present invention are:

[0030] The 4-aryl naphthoimidazole compound of the present invention is easy to synthesize, has extremely strong inhibitory activity against fungi such as apple anthracnose pathogen, apple ring rot pathogen, rice blast pathogen, cabbage black spot pathogen and / or corn Curvularia pathogen, and is significantly stronger than the currently commonly used clinical antifungal drug azoxystrobin.

[0031] The preparation method of the present invention has the advantages of a short synthesis route, simple and readily available raw materials, simple post-processing, and the like, and is suitable for industrial large-scale production. BRIEF DESCRIPTION OF THE DRAWINGS

[0032] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the following briefly introduces the drawings required for use in the embodiments or the description of the prior art. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying any creative work.

[0033] Figure 1 It is sample 1 1 H-NMR spectrum.

[0034] Figure 2 It is sample 1 13 C-NMR spectrum.

[0035] Figure 3 is the HRMS (ESI) spectrum of sample 1.

[0036] Figure 4 It is sample 2 1 H-NMR spectrum.

[0037] Figure 5 It is sample 2 13 C-NMR spectrum.

[0038] Figure 6 This is the HRMS (ESI) spectrum of sample 2.

[0039] Figure 7 It is sample 3 1 H-NMR spectrum.

[0040] Figure 8 It is sample 3 13 C-NMR spectrum.

[0041] Figure 9 This is the HRMS (ESI) spectrum of sample 3.

[0042] Figure 10 It is sample 4 1 H-NMR spectrum.

[0043] Figure 11 It is sample 4 13 C-NMR spectrum.

[0044] Figure 12 This is the HRMS (ESI) spectrum of sample 4. DETAILED DESCRIPTION

[0045] To make the objectives, technical solutions, and advantages of the present invention more apparent, the technical solutions of the present invention will be described in detail below. Obviously, the embodiments described are only some of the embodiments of the present invention, not all of them. Based on the embodiments of the present invention, all other implementations obtained by those of ordinary skill in the art without inventive effort are within the scope of protection of the present invention.

[0046] Example 1

[0047] This embodiment provides a method for preparing a 4-aryl naphthoimidazole compound, the preparation method comprising the following steps:

[0048] (1) Under nitrogen protection, 4,5-diiodo-1-methyl-1H-imidazole (10 mmol) was dissolved in anhydrous tetrahydrofuran (100 mL). After it was fully dissolved, the reaction solution temperature was lowered to 0°C, and C2H5MgBr (3M ether, 3.5 mL, 10.5 mmol) was slowly added dropwise to the above solution. After the addition was complete, the reaction solution temperature was raised to room temperature (20°C) and the reaction was continued with stirring for 2 h to obtain a first reaction solution;

[0049] (2) slowly adding benzaldehyde (11.0 mmol) dropwise to the first reaction solution, stirring and reacting at room temperature (20° C.) for 20 h to obtain a second reaction solution;

[0050] (3) After the reaction, the second reaction solution was quenched with saturated aqueous ammonium chloride solution (80 mL), separated using a separatory funnel, and the organic phase was collected. The aqueous phase was extracted with ethyl acetate (100 mL × 3). The combined organic phases were washed with saturated brine (150 mL), dried over anhydrous Na2SO4, and concentrated. The residue was washed with a small amount of ethyl acetate and filtered to obtain the intermediate with a yield of 69%;

[0051] (4) The intermediate (3.0 mmol) was dissolved in anhydrous tetrahydrofuran (40 mL) under nitrogen protection. At 0°C, C2H5MgBr (3 M ether, 5.6 mL, 16.8 mmol) was slowly added dropwise to the system. The reaction mixture was slowly heated to room temperature (20°C) and stirred for 3 h to obtain a third reaction solution.

[0052] (5) The corresponding substituted benzaldehyde (3.3 mmol, methyl substituted benzaldehyde) was added to the third reaction solution using a syringe, and the reaction was continued at room temperature (20°C) for 20 h. After the reaction was completed, the reaction was quenched with 80 mL of saturated NH4Cl aqueous solution, extracted with ethyl acetate (30 mL×3), and the combined organic phase was washed with saturated brine (30 mL), dried over anhydrous Na2SO4, concentrated, and added with dichloromethane (30 mL). HBr (15 mmol) was added dropwise and stirred at room temperature for 12 h. After the reaction was completed, 30 mL L of water was added to the reaction solution, and the mixture was stirred thoroughly for 10 min. The pH was adjusted to 7 with saturated aqueous NaHCO3 solution, extracted with CH2Cl2 (30 mL×3), and the combined organic phases were washed with saturated brine (30 mL), dried over anhydrous Na2SO4, and concentrated. The residue was purified by silica gel column chromatography using CH2Cl2:EtOAc=5:1 as eluent to obtain the target compound, named Sample 1 (1-methyl-4-(p-tolyl)-1H-naphtho[2,3-d]imidazole). The structural formula of Sample 1 is shown in Formula III.

[0053]

[0054] Example 2

[0055] This embodiment provides a method for preparing a 4-aryl naphthoimidazole compound, the preparation method comprising the following steps:

[0056] (1) Under nitrogen protection, 4,5-diiodo-1-methyl-1H-imidazole (10 mmol) was dissolved in anhydrous tetrahydrofuran (100 mL). After it was fully dissolved, the reaction solution temperature was lowered to 0°C, and C2H5MgBr (3M ether, 3.5 mL, 10.5 mmol) was slowly added dropwise to the above solution. After the addition was complete, the reaction solution temperature was raised to room temperature (25°C) and the reaction was continued with stirring for 2.5 h to obtain a first reaction solution;

[0057] (2) Benzaldehyde (11.0 mmol) was slowly added dropwise to the first reaction solution, and the mixture was stirred at room temperature (25° C.) for 22 h to obtain a second reaction solution;

[0058] (3) After the reaction, the second reaction solution was quenched with saturated aqueous ammonium chloride solution (80 mL), separated using a separatory funnel, and the organic phase was collected. The aqueous phase was extracted with ethyl acetate (100 mL × 3). The combined organic phases were washed with saturated brine (150 mL), dried over anhydrous Na2SO4, and concentrated. The residue was washed with a small amount of ethyl acetate and filtered to obtain the intermediate.

[0059] (4) The intermediate (3.0 mmol) was dissolved in anhydrous tetrahydrofuran (40 mL) under nitrogen protection. At 0°C, C2H5MgBr (3 M ether, 5.6 mL, 16.8 mmol) was slowly added dropwise to the system. The reaction mixture was slowly heated to room temperature (25°C) and stirred for 3.5 h to obtain a third reaction solution.

[0060] (5) The corresponding substituted benzaldehyde (3.3 mmol, ethyl substituted benzaldehyde) was added to the third reaction solution using a syringe, and the reaction was continued at room temperature (25°C) for 22 h. After the reaction was completed, the reaction was quenched with 80 mL of saturated NH4Cl aqueous solution, extracted with ethyl acetate (30 mL×3), and the combined organic phase was washed with saturated brine (30 mL), dried over anhydrous Na2SO4, concentrated, and added with dichloromethane (30 mL). HBr (15 mmol) was added dropwise and stirred at room temperature for 12 h. After the reaction was completed, 30 mL of Water was added to the reaction solution, and the mixture was stirred thoroughly for 10 min. The pH was adjusted to 7 with saturated aqueous NaHCO3 solution, and extracted with CH2Cl2 (30 mL×3). The combined organic phase was washed with saturated brine (30 mL), dried over anhydrous Na2SO4, and concentrated. The residue was purified by silica gel column chromatography using CH2Cl2:EtOAc=5:1 as eluent to obtain the target compound, named Sample 2 (4-(4-ethylphenyl)-1-methyl-1H naphtho[2,3-d]imidazole). The structural formula of Sample 2 is shown in Formula IV.

[0061]

[0062] Example 3

[0063] This embodiment provides a method for preparing a 4-aryl naphthoimidazole compound, the preparation method comprising the following steps:

[0064] (1) Under nitrogen protection, 4,5-diiodo-1-methyl-1H-imidazole (10 mmol) was dissolved in anhydrous tetrahydrofuran (100 mL). After it was fully dissolved, the reaction solution temperature was lowered to 0°C, and C2H5MgBr (3M ether, 3.5 mL, 10.5 mmol) was slowly added dropwise to the above solution. After the addition was complete, the reaction solution temperature was raised to room temperature (30°C) and the reaction was continued with stirring for 3 h to obtain a first reaction solution;

[0065] (2) benzaldehyde (11.0 mmol) was slowly added dropwise to the first reaction solution, and the mixture was stirred at room temperature (30° C.) for 24 h to obtain a second reaction solution;

[0066] (3) After the reaction, the second reaction solution was quenched with saturated aqueous ammonium chloride solution (80 mL), separated using a separatory funnel, and the organic phase was collected. The aqueous phase was extracted with ethyl acetate (100 mL × 3). The combined organic phases were washed with saturated brine (150 mL), dried over anhydrous Na2SO4, and concentrated. The residue was washed with a small amount of ethyl acetate and filtered to obtain the intermediate.

[0067] (4) The intermediate (3.0 mmol) was dissolved in anhydrous tetrahydrofuran (40 mL) under nitrogen protection. At 0°C, C2H5MgBr (3 M ether, 5.6 mL, 16.8 mmol) was slowly added dropwise to the system. The reaction mixture was slowly heated to room temperature (30°C) and stirred for 4 h to obtain a third reaction solution.

[0068] (5) The corresponding substituted benzaldehyde (3.3 mmol, isopropyl substituted benzaldehyde) was added to the third reaction solution using a syringe, and the reaction was continued at room temperature (30°C) for 24 h. After the reaction was completed, the reaction was quenched with 80 mL of saturated NH4Cl aqueous solution, extracted with ethyl acetate (30 mL×3), and the combined organic phase was washed with saturated brine (30 mL), dried over anhydrous Na2SO4, concentrated, and added with dichloromethane (30 mL). HBr (15 mmol) was added dropwise and stirred at room temperature for 12 h. After the reaction was completed, 30 mL L of water was added to the reaction solution, and the mixture was stirred thoroughly for 10 min. The pH was adjusted to 7 with saturated aqueous NaHCO3 solution, and extracted with CH2Cl2 (30 mL×3). The combined organic phases were washed with saturated brine (30 mL), dried over anhydrous Na2SO4, and concentrated. The residue was purified by silica gel column chromatography using CH2Cl2:EtOAc=5:1 as eluent to obtain the target compound, named Sample 3 (4-(4-isopropylphenyl)-1-methyl-1H-naphtho[2,3-d]imidazole). The structural formula of Sample 3 is shown in Formula V.

[0069]

[0070] Example 4

[0071] This embodiment provides a method for preparing a 4-aryl naphthoimidazole compound, the preparation method comprising the following steps:

[0072] (1) Under nitrogen protection, 4,5-diiodo-1-methyl-1H-imidazole (10 mmol) was dissolved in anhydrous tetrahydrofuran (100 mL). After it was fully dissolved, the reaction solution temperature was lowered to 0°C, and C2H5MgBr (3M ether, 3.5 mL, 10.5 mmol) was slowly added dropwise to the above solution. After the addition was complete, the reaction solution temperature was raised to room temperature (20°C) and the reaction was continued with stirring for 3 h to obtain a first reaction solution;

[0073] (2) Benzaldehyde (11.0 mmol) was slowly added dropwise to the first reaction solution, and the mixture was stirred at room temperature (20° C.) for 24 h to obtain a second reaction solution;

[0074] (3) After the reaction, the second reaction solution was quenched with saturated aqueous ammonium chloride solution (80 mL), separated using a separatory funnel, and the organic phase was collected. The aqueous phase was extracted with ethyl acetate (100 mL × 3). The combined organic phases were washed with saturated brine (150 mL), dried over anhydrous Na2SO4, and concentrated. The residue was washed with a small amount of ethyl acetate and filtered to obtain the intermediate.

[0075] (4) The intermediate (3.0 mmol) was dissolved in anhydrous tetrahydrofuran (40 mL) under nitrogen protection. At 0°C, C2H5MgBr (3 M ether, 5.6 mL, 16.8 mmol) was slowly added dropwise to the system. The reaction mixture was slowly heated to room temperature (20°C) and stirred for 4 h to obtain a third reaction solution.

[0076] (5) The corresponding substituted benzaldehyde (3.3 mmol, chlorine-substituted benzaldehyde) was added to the third reaction solution using a syringe, and the reaction was continued at room temperature (20°C) for 24 h. After the reaction was completed, the reaction was quenched with 80 mL of saturated NH4Cl aqueous solution, extracted with ethyl acetate (30 mL×3), and the combined organic phase was washed with saturated brine (30 mL), dried over anhydrous Na2SO4, concentrated, and added with dichloromethane (30 mL). HBr (15 mmol) was added dropwise and stirred at room temperature for 12 h. After the reaction was completed, 30 mL of Water was added to the reaction solution, and the mixture was stirred thoroughly for 10 min. The pH was adjusted to 7 with saturated aqueous NaHCO3 solution, and extracted with CH2Cl2 (30 mL×3). The combined organic phase was washed with saturated brine (30 mL), dried over anhydrous Na2SO4, and concentrated. The residue was purified by silica gel column chromatography using CH2Cl2:EtOAc=5:1 as eluent to obtain the target compound, named Sample 4 (4-(4-chlorophenyl)-1-methyl-1H-naphtho[2,3-d]imidazole). The structural formula of Sample 4 is shown in Formula VI.

[0077]

[0078] Test example

[0079] (1) Compound structure identification

[0080] The present invention uses nuclear magnetic resonance ( 1 H-NMR, 13 The structure of the synthesized 4-aryl-naphthoimidazole compound was identified by C-NMR and high-resolution mass spectrometry (HRMS). The following is the specific structural formula and structural identification of the compound:

[0081] Sample 1: 1-methyl-4-(p-tolyl)-1H-naphtho[2,3-d]imidazole

[0082] White solid, Yield: 78.64%, mp204.3-205.5℃;

[0083] 1 H NMR (400MHz, CDCl3) δ8.06-7.98(m,3H), 7.79(s,1H), 7.51(d,J=8.1Hz,2H), 7.46-7.42(m,1H), 7.38-7.32(m,3H), 3.91(s,3H), 2.46(s,3H);

[0084] 13 C NMR (100MHz, CDCl3) δ147.43, 141.99, 137.17, 134.74, 133.49, 130.99, 130.95, 129.75, 129.09, 128.19, 127.79, 126.53, 124.40, 123.53, 104.71, 31.21, 21.40.

[0085] HR-ESI-MS[M+H] + calcd for C 19 H 17 N2 + , 273.1386, found 273.1380.

[0086] Among them, the NMR of sample 1 ( 1 H-NMR, 13 C-NMR) and high resolution mass spectrometry (HRMS) were respectively Figures 1 to 3 shown.

[0087] Sample 2: 4-(4-ethylphenyl)-1-methyl-1H-naphtho[2,3-d]imidazole

[0088] White solid, Yield: 75.36%, mp193.0-194.0℃;

[0089] 1 H NMR (400MHz, CDCl3) δ8.08-7.99 (m, 3H), 7.79 (s, 1H), 7.54 (d, J = 8.1Hz, 1H), 7.47-7.3 9(m,3H), 7.36-7.31(m,1H), 3.92(s,3H), 2.77(q,J=7.6Hz,2H), 1.34(t,J=7.6Hz,3H);

[0090] 13 C NMR (100MHz, CDCl3) δ147.47, 143.34, 142.24, 134.83, 133.76, 131.06, 130.94, 129 .86, 128.17, 127.89, 127.78, 126.59, 124.36, 123.46, 104.65, 31.19, 28.81, 15.56.

[0091] HR-ESI-MS[M+H] + calcd for C 20 H 19 N2 + , 287.1543, found 287.1544.

[0092] Among them, the NMR of sample 2 ( 1 H-NMR, 13 C-NMR) and high resolution mass spectrometry (HRMS) were respectively Figures 4 to 6 shown.

[0093] Sample 3: 4-(4-isopropylphenyl)-1-methyl-1H-naphtho[2,3-d]imidazole

[0094] White solid, Yield: 66.13%, mp134.0-134.5℃;

[0095] 1 H NMR (400MHz, CDCl3) δ8.09-7.99(m,3H), 7.80(s,1H), 7.57-7.54(m,2H), 7.47-7.41( m,3H), 7.37-7.33(m,1H), 3.93(s,3H), 3.03(p,J=6.9Hz,1H), 1.35(d,J=6.9Hz,6H);

[0096] 13C NMR (100MHz, CDCl3) δ147.86, 147.47, 142.11, 134.80, 133.81, 131.03, 130.95, 129 .87, 128.21, 127.77, 126.64, 126.47, 124.38, 123.47, 104.66, 34.06, 31.21, 24.10.

[0097] HR-ESI-MS[M+H] + calcd for C 21 H 21 N2 + , 301.1699, found 301.1699.

[0098] Among them, the NMR of sample 3 ( 1 H-NMR, 13 C-NMR) and high resolution mass spectrometry (HRMS) were respectively Figures 7 to 9 shown.

[0099] Sample 4: 4-(4-chlorophenyl)-1-methyl-1H-naphtho[2,3-d]imidazole

[0100] White solid, Yield: 64.71%, mp259.4-259.6℃;

[0101] 1 H NMR (400MHz, Chloroform-d) δ8.11 (s, 1H), 8.02 (d, J = 8.4Hz, 1H), 7.97 (d, J = 8.7Hz, 1H ), 7.84(s,1H), 7.57-7.52(m,4H), 7.49-7.45(m,1H), 7.39-7.36(m,1H), 3.96(s,3H);

[0102] 13 C NMR (100MHz, CDCl3) δ147.64, 141.95, 135.01, 134.68, 133.58, 132.54, 130.89, 128.62, 128.13, 127.95, 125.99, 124.54, 123.94, 105.38, 31.27.

[0103] HR-ESI-MS[M+H] + calcd for C 18 H 14 ClN2 + , 293.0840, found 293.0840.

[0104] Among them, the NMR of sample 4 ( 1 H-NMR, 13 C-NMR) and high resolution mass spectrometry (HRMS) were respectively Figures 10 to 12 shown.

[0105] (2) Experiments on pharmacological effects

[0106] Experimental Materials:

[0107] In vitro pharmacological studies were conducted on the aforementioned compounds (Samples 1-4) using the in vitro linear mycelial growth rate method. Antifungal activity was tested against five plant pathogens, including apple anthrax, apple striata, rice blast, cabbage black spot, and corn Curvularia zea. The antifungal activity of each test compound was compared with that of the commonly used antifungal drug azoxystrobin. The results demonstrate that the 4-arylnaphthoimidazole compounds described herein are effective agents against plant pathogens. The tested plant pathogens are listed in Table 1.

[0108] Table 1 Plant pathogenic fungi tested

[0109] Fungus name Latin name abbreviation Apple Anthracnose Colletotrichum gloeosporioides CG Apple ring rot pathogen <![CDATA[ Physalospora piricola Nose]]> PPN Rice blast pathogen Pyricularia oryza PO Black spot pathogen of cabbage Altrnaria brassicae AB Curvularia spp. Curvularia lunata CL

[0110] Taking apple anthrax, apple stigma, rice blast, cabbage black spot and corn curvature as examples, the specific operation is as follows:

[0111] Preparation of PDA culture medium: Select potatoes, wash and peel them, accurately weigh 200g, and cut them into small pieces. Then, place the cut potato pieces in a container and add 2000mL of ultrapure water. Heat the mixture until it boils. After boiling, reduce the heat to a low simmer and maintain it at a slight boil for 30 minutes. After heating, filter it while it is still hot through three layers of gauze. Collect the filtrate. If the volume of the filtrate is less than 1000mL, adjust the volume to 1000mL with ultrapure water. To the 1000mL filtrate obtained, add 20g of glucose and 15g of agar in sequence. After addition, stir thoroughly with a glass rod to evenly disperse the glucose and agar in the filtrate. Quickly divide the mixed liquid into Erlenmeyer flasks according to the volume required for the experiment. Seal the Erlenmeyer flasks containing the culture medium with sterile breathable sealing film. After sealing, place the conical flask in an autoclave and sterilize at 0.11 MPa and 120°C for 30 minutes. After sterilization, the culture medium is ready for subsequent use.

[0112] Activate the test bacteria: Remove the sealed test tube containing the bacterial strain from the refrigerator at approximately 4°C. Under sterile conditions, inoculate the pathogenic fungus onto a pre-sterilized, solidified PDA medium plate using the streak method. Place the inoculated plate in an artificial climate chamber and incubate at 25°C and 65% humidity for 3-5 days. Regularly observe the size of the colonies on the plate. When the colonies have grown to 2 / 3 of the plate area, the activated strain is ready for use in subsequent experiments.

[0113] Initial screening for antifungal activity: Accurately weigh the test drug (30 μmol) using a 1 / 10,000th balance and place it in a small sample vial. Add 0.5 mL of DMSO to the vial to completely dissolve the test drug. Once dissolved, add 9.5 mL of sterile water for dilution. Under the sterile conditions of a clean bench, pour the solution into 190 mL of autoclaved PDA culture medium at approximately 50°C. After pouring, shake thoroughly to ensure uniform mixing of the drug and culture medium. While still hot, pour the medium containing the drug solution into culture dishes, adding approximately 18 mL to each dish. The final concentration of the drug solution in the dish is 150 μM, and the DMSO concentration is 0.25% (v / v). Experiments have confirmed that 0.25% DMSO in the culture medium has no significant effect on fungal growth. The culture medium containing 0.25% DMSO serves as a blank control. After the culture medium plate is completely solidified, use a pre-sterilized puncher (diameter d = 5 mm) to punch holes on the activated bacterial colony to obtain a bacterial cake. Use an inoculation needle to carefully inoculate the bacterial cake (d = 5 mm) in the center of the culture medium plate, making sure that the side containing mycelium is facing down and tightly attached to the culture medium. Mark the inoculated plate and place it in an incubator for incubation at a temperature of 25°C and a humidity of 65%. Set up three parallel samples for each experiment. After 72 hours of incubation, the diameter of the colony is measured using the cross-cross method (unit: mm). Then, calculate the inhibition rate of mycelial growth according to the following formula.

[0114]

[0115] Test results: The inhibition rates of the test compounds at a concentration of 150 μM against five plant pathogenic fungi, namely, apple anthracnose, apple striata, rice blast, cabbage black spot and corn curvature, are shown in Table 2:

[0116] Table 2 Inhibitory effect of samples at 150 μM concentration on plant pathogenic fungi for 72 h

[0117]

[0118] Antifungal potency assay: The present invention uses the half-dilution method to prepare the liquid. The specific operation is as follows: weigh 60 μmol of the test compound, add 0.5 mL of DMSO to completely dissolve the sample, and then add 9.5 mL of sterile water; use the half-dilution method to prepare 7 concentrations of the test solution; pour the prepared test solution (5 mL) into 195 mL of culture medium, and after mixing, a culture medium with a concentration gradient of 150, 75, 37.5, 18.75, 9.375, 4.6875, and 2.34375 μM can be obtained, and the concentration of DMSO in the culture medium is 0.25% (v / v). According to the initial screening method, the dish is poured, inoculated, cultured, and the diameter is measured, and the inhibition rate is calculated. Three parallel groups are set for each experiment. Ensure that there are 5 suitable concentrations within the linear range (20%-80%). The results are shown in Table 3.

[0119] Table 3 EC of samples 50 Value (72h) and toxicity equation

[0120]

[0121] Note: y is the probability value of the average inhibition rate; x is the logarithm of mass concentration lg [C (μM)].

[0122] The results showed that, compared with the commonly used antifungal drug azoxystrobin, the test compounds (samples 1-4) exhibited moderate inhibitory activity against five plant pathogens: apple anthracnose, apple scab, rice blast, cabbage black spot, and corn Curvularia. Specifically, samples 1-4 exhibited higher inhibitory activity than azoxystrobin against apple anthracnose; samples 2 and 3 exhibited higher inhibitory activity than azoxystrobin against apple scab; samples 1-4 exhibited higher inhibitory activity than azoxystrobin against rice blast; samples 1-3 exhibited higher inhibitory activity than azoxystrobin against cabbage black spot; and samples 1-4 all exhibited higher inhibitory activity than azoxystrobin against corn Curvularia.

[0123] The above description is merely a specific embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Any modifications or substitutions that can be easily conceived by a person skilled in the art within the technical scope disclosed in the present invention should be included in the scope of protection of the present invention. Therefore, the scope of protection of the present invention should be based on the scope of protection of the claims.

Claims

1. A 4-aryl naphthoimidazole compound, characterized in that The chemical structural formula is shown in Formula I: Wherein, R is methyl, ethyl, isopropyl or chlorine.

2. The method for preparing the 4-aryl naphthoimidazole compound according to claim 1, wherein The preparation method comprises the following steps: (1) Under an inert gas atmosphere, 4,5-diiodo-1-methyl-1H-imidazole is dissolved in anhydrous tetrahydrofuran, and C2H5MgBr is added after dissolution, and then stirred under heating conditions to react to obtain a first reaction solution; (2) adding benzaldehyde to the first reaction solution, maintaining the temperature and continuing to stir the reaction to obtain a second reaction solution; (3) quenching the second reaction solution, separating the liquid, collecting the organic phase, washing, drying, concentrating, and filtering to obtain an intermediate; (4) dissolving the intermediate in anhydrous tetrahydrofuran, adding C2H5MgBr, and stirring under heating conditions to react to obtain a third reaction solution; (5) adding substituted benzaldehyde to the third reaction solution to continue the reaction, removing the Grignard reagent after completion, then adding dichloromethane and HBr to carry out cyclization, and finally purifying to obtain the corresponding 4-aryl naphthoimidazole compound.

3. The method for preparing a 4-aryl naphthoimidazole compound according to claim 2, wherein: In step (1): The inert gas atmosphere is a nitrogen atmosphere; And / or, the heating temperature is 20-30° C., and the reaction time is 2-3 hours.

4. The method for preparing a 4-aryl naphthoimidazole compound according to claim 2, wherein: In step (2), the reaction temperature is 20-30° C., and the reaction time is 20-24 h.

5. The method for preparing the 4-aryl naphthoimidazole compound according to claim 2, wherein: In step (3), the second reaction solution is quenched with a saturated aqueous ammonium chloride solution, and then separated using a separatory funnel and the organic phase is collected; the aqueous phase is extracted with ethyl acetate, and the combined organic phases are washed with saturated brine, dried over anhydrous Na2SO4, and concentrated; the residue is washed with ethyl acetate and filtered to obtain an intermediate.

6. The method for preparing the 4-aryl naphthoimidazole compound according to claim 2, wherein: In step (4), the heating temperature is 20-30° C., and the reaction time is 3-4 h.

7. The method for preparing the 4-aryl naphthoimidazole compound according to claim 2, wherein: In step (5): The substituted benzaldehyde is methyl substituted benzaldehyde, ethyl substituted benzaldehyde, isopropyl substituted benzaldehyde or chlorine substituted benzaldehyde; And / or, the reaction temperature is 20-30° C., and the reaction time is 20-24 h; And / or, the ring closing temperature is 20-30° C., and the ring closing time is 12-14 hours.

8. Use of the 4-aryl naphthoimidazole compound according to claim 1 in the preparation of antifungal drugs.

9. The use according to claim 9, characterized in that The fungi are apple anthracnose pathogen, apple ring rot pathogen, rice blast pathogen, cabbage black spot pathogen and / or corn Curvularia spp. pathogen.

10. An antifungal drug, characterized in that: The antifungal drug comprises the 4-aryl naphthoimidazole compound according to claim 1.

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