Compounds of the adamantane isopropanolamine structure, their preparation method and use

Abstract

The present application relates to a kind of adamantane isopropanol amine structure compound and its preparation method and purposes.The compound has the structure as shown in general formula (I):The present application is based on adamantane compound, isopropanol amine fragment is introduced into this system, synthesizes a series of adamantane isopropanol amine compound, and the compound has good inhibitory effect on plant pathogenic bacteria.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of pharmaceutical chemistry, and particularly relates to an isopropanolamine compound containing adamantane amide as well as a preparation method and application thereof. BACKGROUND

[0002] In recent years, plant bacterial diseases caused by pathogenic bacteria seriously affect the yield and quality of global crops, and are one of the main reasons for the yield loss of economic crops in the world. Among them, Xanthomonas oryzae pv. Oryzae and Xanthomonas axonopodis pv. Citri are typical gram-negative Xanthomonas, which respectively cause serious rice bacterial leaf blight and citrus canker disease. For example, Xanthomonas oryzae pv. Oryzae can cause rice leaf blight and whitening, and causes the global rice yield to decrease by 10-50% annually; Xanthomonas axonopodis pv. Citri can cause obvious yellow spots on citrus leaves and fruit rot, and has a serious impact on global citrus production. In the process of agricultural production, due to the long-term use of traditional pesticides, plant pathogens have developed certain resistance to them. Therefore, it is of great significance to create new green pesticides with high efficiency, low toxicity and safety.

[0003] According to literature reports, adamantane and its derivatives have broad-spectrum biological activity, and the research on adamantane and its derivatives mainly focuses on antibacterial, antituberculosis, anticancer, antiviral, anti-inflammatory and anti-Parkinson's disease, etc.; at the same time, in the aspect of antibacterial, Staphylococcus aureus, Bacillus subtilis, Escherichia coli, Pseudomonas aeruginosa and other pathogenic microorganisms have good biological activity, and such compounds are being vigorously developed for other fields. In order to find high-efficiency antibacterial active compounds, the present application ingeniously introduces an isopropanolamine skeleton into the system based on the adamantane structure and acylamide bond as the connecting chain, and synthesizes a series of isopropanolamine compounds with adamantane amide structure, so as to investigate the biological activity and provide an important scientific basis for the research and development of new pesticides.

[0004] The research progress of the biological activity of adamantane compounds is as follows:

[0005] In 2017, Maria Fesatidou et al. [Fesatidou, M.; Zagaliotis, P.; Camoutsis, C.; Petrou, A.; Eleftheriou, P.; Tratrat, C.; Haroun, M.; Geronikaki, A.; Ciric, A.; Sokovic, M. 5-Adamantan thiadiazole-based thiazolidinones as antimicrobial agents. Design, synthesis, molecular docking and evaluation. Bioorg. Med. Chem. 2018, 26: 4664-4676.] designed and synthesized a series of 5-adamantan thiadiazole-based thiazolidinones, and evaluated their antibacterial activity against 8 Gram-positive and Gram-negative bacteria by 1 H NMR, 13 C NMR and HRMS. The results showed that all the compounds had antibacterial activity against 8 Gram-positive and Gram-negative bacteria, 12 of the 17 compounds were more effective than streptomycin, and all the compounds were more effective than ampicillin; in addition, all the compounds had better antifungal activity than the control drugs biphenylazole and ketoconazole (3-115 times).

[0006] In 2019, Van Hien Pham et al. [Pham, V. H.; Phan, T. P. D.; Phan, D. C.; Vu, B. D. Synthesis and Bioactivity of Thiosemicarbazones Containing Adamantane Skeletons. Molecules. 2020, 25: 1-14.] designed and synthesized a series of novel aminothiosemicarbazones containing adamantane skeletons, and evaluated their antibacterial activity against 8 Gram-positive and Gram-negative bacteria by 1 H NMR, 13 C NMR and HRMS. The results showed that most of the compounds had good antibacterial activity against Enterococcus faecalis, Staphylococcus aureus, Bacillus cereus and Candida albicans. Among them, compound 2a had lower IC 50 values of 4.78, 4.12 and 6.78 μM against Staphylococcus aureus, Bacillus cereus and Candida albicans, respectively.

[0007] In 2020, Lamya H. Al-Wahaibi et al. [Al-Wahaibi, L. H.; Alvarez, N.; Blacque, O.; Veiga, N.; Al-Mutairi, A. A.; El-Emam, A. A. Synthesis and Structure Insights of Two Novel Broad-Spectrum Antibacterial Candidates Based on (E)-N'-[(Heteroaryl)methylene]adamantane-1-carbohydrazides. Molecules. 2020, 25: 1-17.] synthesized two novel adamantane-1-hydrazide derivatives and characterized their chemical structures by 1 H NMR, 13 C NMR, infrared and ultraviolet-visible spectroscopy, and single-crystal X-ray diffraction. In the antibacterial activity test, compounds 1 and 2 had good inhibitory effect on both gram-positive and gram-negative bacteria, and the MIC values against Staphylococcus aureus were 3.53 μg / mL and 1.50 μg / mL, respectively, which exceeded that of the antibacterial drug ampicillin (5.72 μg / mL).

[0008] In 2022, Eman T. Warda et al. [Warda, E. T.; El-Ashmawy, M. B.; Habib, E. E.; Abdelbaky, M. S. M.; Garcia-Granda, S.; Thamotharan, S.; El-Emam, A. A. Synthesis and in vitro antibacterial, antifungal, anti-proliferative activities of novel adamantane-containing thiazole compounds. Sci. Rep. 2022, 12: 21058.] designed and synthesized a series of adamantane thiazole compounds, and characterized their chemical structures by 1 H NMR, 13The structure of the synthetic compound was characterized by C NMR and x-ray crystallography. The antibacterial activity test results on plant pathogenic fungi and bacteria showed that compound 5c exhibited broad-spectrum antibacterial bioactivity, with MIC values of 2.0, 4.0, 3.0, 6.5 and 10.25 μg / mL for Staphylococcus aureus, Bacillus subtilis, Micrococcus luteus, Escherichia coli and Pseudomonas aeruginosa, respectively; in addition, the antiproliferative activity of the synthesized compounds on five human tumor cell lines was evaluated, and the results showed that compounds 5e and 5k had the best antiproliferative activity and had strong inhibition on all cell lines.

[0009] In 2022, Ji et al. [Ji, Q., Mu, X., Hu, D., Fan, L, Xiang, S., Ye, H., Gao, X., & Wang, P. Fabrication of Host-Guest Complexes between Adamantane-Functionalized 1, 3, 4-Oxadiazoles and β-Cyclodextrin with Improved Control Efficiency against Intractable Plant Bacterial Diseases. ACS Applied Materials & Interfaces. 2022, 14: 2564-2577.] designed and synthesized a series of adamantane derivatives containing 1, 3, 4-oxadiazole; preliminary antibacterial activity screening showed that most of the adamantane derivatives containing 1, 3, 4-oxadiazole had obvious bioactivity against three typical destructive plant pathogenic bacteria. Among them, the compounds with high in vitro activity against Xoo, Xac and Psa were 7a (0.936 μg / mL), 7a (0.889 μg / mL) and 7b (2.10 μg / mL), respectively; all of which were better than the control drugs BT (39.0, 56.5 and 118 μg / mL) and TC (62.3, 69.8 and 74.5 μg / mL). 50 SUMMARY

[0010] One of the purposes of the present application is to provide an adamantane-containing amide compound or a stereoisomer thereof, or a salt or a solvate thereof.

[0011] Another purpose of the present application is to provide an intermediate compound for preparing the above-mentioned compound or a stereoisomer thereof, or a salt or a solvate thereof, and a preparation method thereof.

[0012] ​The present application also aims to provide a composition containing the compound or its stereoisomer, or its salt or its solvate.

[0013] The present application also aims to provide the use of the compound or its stereoisomer, or its salt or its solvate, or the composition.

[0014] The present application also aims to provide a method for preventing and treating agricultural pests and diseases by using the compound or its stereoisomer, or its salt or its solvate, or the composition.

[0015] To achieve the above-mentioned purposes, the present application adopts the following technical solutions:

[0016] An amide compound of adamantane or its stereoisomer, or its salt or its solvate, the compound has a structure as shown in general formula (I):

[0017]

[0018] wherein R1 and R2 are each independently selected from one or more of hydrogen, optionally substituted or unsubstituted alkyl, optionally substituted or unsubstituted aryl, and optionally substituted or unsubstituted heteroaryl; or R1 and R2 are bonded to form a substituted or unsubstituted alicyclic ring.

[0019] Preferably, R1 is selected from hydrogen, methyl, ethyl; R2 is selected from methyl, phenyl, fluorophenyl, difluorophenyl, benzyl, methylbenzyl, tert-butylbenzyl, fluorobenzyl, trifluoromethylbenzyl, dichlorobenzyl, methoxybenzyl, dimethoxybenzyl; when R1 and R2 are bonded to form a ring, it is tetrahydropyrrole, piperazine; most preferably, R1 is selected from hydrogen, and R2 is selected from tert-butylbenzyl.

[0020] wherein the substituents on the phenyl group, if not specified, indicate that the substituents can be substituted at any position on the phenyl ring. For example, difluorophenyl indicates that the two fluorines can be at the ortho, meta or para position, and correspondingly, the N atom can be connected at any position on the phenyl ring.

[0021] By adopting the above technical solutions, the present application synthesizes a series of amide compounds containing adamantane by using adamantane as a starting material, and it is found that the compound has a good inhibitory effect on pathogenic plant pathogenic bacteria, such as Xanthomonas oryzae pv. oryzae (Xoo), Xanthomonas axonopodis pv. Citri (Xac), Xanthomnas citri pv. Mangiferaeindicae (Xcm) and the like, which provides an important scientific basis for the research and development of new pesticides. BRIEF DESCRIPTION OF DRAWINGS

[0022] Figure 1 is the control effect of compound 8, 8@β-CD, β-CD and other related compounds on rice bacterial leaf blight;

[0023] Figure 2 is the control effect of compound 8, 8@β-CD, β-CD and other related compounds on citrus canker; Examples

[0024] The application will be further described by the following examples. It should be understood that the methods described in the examples of the application are only used to illustrate the application, but not to limit the application, and the simple improvement of the preparation method of the application under the concept of the application belongs to the scope of the application claimed. All raw materials and solvents used in the examples are commercially available.

[0025] Example 1: Preparation of intermediate N-((3S,5S,7S)-adamantane-1-yl)-3- hydroxybenzamide

[0026] 1-adamantamine (2.0 g, 13.2 mmol), 3-hydroxybenzoic acid (1.8 g, 13.2 mmol), benzotriazol-N, N, N', N'-tetramethyluronium hexafluorophosphate borate (5.1 g, 15.9 mmol), N, N-diisopropylethylamine (4.6 mL, 26.5 mmol) and 4-dimethylaminopyridine (0.32 g, 2.64 mmol) were mixed in a 100 mL round-bottom flask with dichloromethane (60 mL) as the solvent. The mixture was reacted at room temperature for 8 hours until the reaction was completed. Then a saturated salt solution (180 mL) was added and extracted with dichloromethane (40 mL). The organic phase was collected, dried over anhydrous Na2SO4, and the organic layer was concentrated under reduced pressure. Column chromatography purification was performed with ethyl acetate / petroleum ether (gradient from 5 / 1 to 3 / 1, v / v) to obtain intermediate 1 (white solid powder, 2.2 g, 8.11 mmol, yield 62%). Its nuclear magnetic resonance data are as follows: 1 H NMR (500 MHz, CDCl3) δ 7.96 (s, 1H, -OH), 7.71 (t, J = 2.2 Hz, 1H, phenyl-H), 7.24 (t, J = 7.9 Hz, 1H, phenyl-H), 7.06 (d, J = 9.0 Hz, 1H, phenyl-H), 6.99 (dd, J = 8.1, 2.6 Hz, 1H, phenyl-H), 5.94 (s, 1H, -NH-CO), 2.12 (d, J = 12.1 Hz, 9H, adamantane-H), 1.72 (s, 6H, adamantane-H).

[0027] Example 2: Preparation of intermediate N-((3S,5S,7S)-adamantan-l-yl)-3- (oxiran-2-ylmethoxy)benzamide

[0028] N-((3S,5S,7S)-adamantan-l-yl)-3-hydroxybenzamide (700 mg, 2.58 mmol), epibromohydrin (459.35 mg, 3.35 mmol) and KOH (217 mg, 3.87 mmol) were mixed in a 100 mL round bottom flask, after reaction at 0 °C for 40 minutes, the reaction was continued at room temperature for 6 hours until the reaction was complete. The reaction mixture was dissolved with ethyl acetate (30 mL) and washed with saturated ammonium chloride (3 x 50 mL). The organic phase was collected, dried over anhydrous Na2SO4, the organic layer was concentrated under reduced pressure, purified by column chromatography with petroleum ether / ethyl acetate (5 / 1, v / v) to give intermediate 2 (white solid powder, 701 mg, 2.14 mmol, 83%). Its NMR data were: 1 H NMR (500 MHz, CDC13) δ 7.33 (t, J = 2.1 Hz, 1H, phenyl-H), 7.30 (d, J = 7.9 Hz, 1H, phenyl-H), 7.26-7.23 (m, 1H, phenyl-H), 7.03 (ddd, J = 8.1, 2.7, 1.1 Hz, 1H, phenyl-H), 5.81 (s, 1H, -NH-CO), 4.31 (dd, J = 11.1, 2.9 Hz, 1H, methylene-H), 3.96 (dd, J = 11.0, 5.9 Hz, 1H, methylene-H), 3.37 (ddt, J = 5.7, 4.1, 2.7 Hz, 1H, methine-H), 2.92 (dd, J = 4.9, 4.1 Hz, 1H, oxirane-H), 2.77 (dd, J = 4.9, 2.7 Hz, 1H, oxirane-H), 2.11 (s, 9H, adamantane-H), 1.71 (s, 6H, adamantane-H).

[0029] Example 3: Preparation of N-((3s,5s,7s)-adamantanamine-l-yl)-3-(3-(benzyl(methyl)amino)- 2-hydroxypropoxy)benzamide

[0030] N-((3S,5S,7S)-adamantan-l-yl)-3-(oxan-2-ylmethoxy)benzamide (0.855 mmol), aniline (1.28 mmol) and potassium carbonate (0.684 mmol) and 5 mL of isopropanol were added to a 15 mL pressure tube and reacted at 55 °C for 20 hours. The mixture was washed with dichloromethane (50 mL x 3) and water (20 mL x 3). The organic layer was dried over anhydrous sodium sulfate and concentrated in vacuo. Purification by column chromatography with dichloromethane / methanol gradient (100 / 1, v / v) as eluent gave the target compound. (pale yellow oil, yield 89.5%)

[0031] Example 4: Preparation of N-((3s,5s,7s)-adamantan-l-yl)-3-(2-hydroxy-3-(phenylamino))propoxy)benzamide

[0032] N-((3S,5S,7S)-adamantan-l-yl)-3-(oxan-2-ylmethoxy)benzamide (0.855 mmol), aniline (1.28 mmol) and potassium carbonate (0.684 mmol) and 5 mL of isopropanol were added to a 15 mL pressure tube and reacted at 55 °C for 20 hours. The mixture was washed with dichloromethane (50 mL x 3) and water (20 mL x 3). The organic layer was dried over anhydrous sodium sulfate and concentrated in vacuo. Purification by column chromatography with dichloromethane / methanol gradient (100 / 1, v / v) as eluent gave the target compound. (pale yellow oil, yield 89.5%)

[0033] Example 5: Preparation of N-((3s,5s,7s)-adamantan-l-yl)-3-(3-(4-(tert-butyl))benzyl)amino)-2-hydroxypropoxy)benzamide

[0034] N-((3S,5S,7S)-adamantan-l-yl)-3-(oxan-2-ylmethoxy)benzamide (0.855 mmol), aniline (1.28 mmol) and potassium carbonate (0.684 mmol) and 5 mL of isopropanol were added to a 15 mL pressure tube and reacted at 55 °C for 20 hours. The mixture was washed with dichloromethane (50 mL x 3) and water (20 mL x 3). The organic layer was dried over anhydrous sodium sulfate and concentrated in vacuo. Purification by column chromatography with dichloromethane / methanol gradient (100 / 1, v / v) as eluent gave the target compound. (pale yellow oil, yield 89.5%)

[0035] Example 4: Preparation of binary complex 8@β-CD

[0036] A solution of guest molecule 8 (8.0 μL, 101.9 mM) in tetrahydrofuran was gradually added into 2.0 mL of deionized water containing host molecule β-CD (0.408 mM). After waiting for the THF to evaporate naturally, the self-assembled supramolecular binary complex 8@β-CD was formed.

[0037] Other compounds were prepared by replacing the corresponding starting materials in the similar manner as in Example 1-5.

[0038] The structure, 1H NMR and 13C NMR data of the synthesized substituted phenyl isopropyl amine compounds are shown in Table 1, and the physicochemical properties are shown in Table 2.

[0039] Table 1 1H NMR and 13C NMR data of the compounds

[0040]

[0041]

[0042]

[0043]

[0044]

[0045]

[0046] Table 2 Physicochemical properties of the target compounds

[0047]

[0048]

[0049] Pharmacological Example 1:

[0050] EC 50 The median effective concentration (EC) is an important indicator for evaluating the sensitivity of plant pathogens to compounds, and is also an important parameter for setting the concentration of the target compound when studying the mechanism of action. In the concentration gradient experiment, five appropriate concentrations were set by using the double dilution method, and finally the inhibition rate of the fungicide on the plant pathogen and the concentration of the fungicide were converted into logarithmic values. Through regression analysis by SPSS software, the virulence curve was obtained, and the EC 50 .

[0051] The effective concentration EC 50, test object is Xoo and Xac. DMSO dissolved in the culture medium as a blank control. The Xoo (rice bacterial blight pathogen in M210 solid medium) is put into NB medium, and is cultured in a constant temperature shaker at 28°C, 180 rpm to the logarithmic growth phase for standby; the Xac (in M210 solid medium) is put into NB medium, and is cultured in a constant temperature shaker at 28°C, 180 rpm to the logarithmic growth phase for standby. The drug (compound) is configured into different concentrations (for example: 100, 50, 25, 12.5, 6.25 μg / mL) of NB liquid medium containing poison 5 mL into the test tube, 40 μL of NB liquid medium containing plant disease bacteria is added respectively, and is oscillated in a constant temperature shaker at 28-30°C, 180 rpm, and the Xoo is cultured for 36 h, and the Xac is cultured for 48 h. The OD 595 value of each concentration of bacterial liquid is determined on a spectrophotometer, and the OD 595 value of the corresponding concentration of sterile NB liquid medium containing poison is additionally determined.

[0052] The corrected OD value = the OD value of the bacterial culture medium - the OD value of the sterile culture medium

[0053] The inhibition rate % = [(the OD value of the corrected control medium bacterial liquid - the OD value of the corrected toxic culture medium) / the OD value of the corrected control medium bacterial liquid] x 100

[0054] The embodiments of the present application assist in illustrating the technical solutions of the present application, but the contents of the embodiments are not limited thereto, and the experimental results of the target compounds are shown in Tables 3 and 4.

[0055] Table 3 Activity of isopropanolamine compounds containing adamantane on plant pathogenic bacteria in preliminary screening

[0056]

[0057] “TC” represents a commercially available drug, “KSM” represents a commercially available drug, and “KSM” represents a commercially available drug.

[0058] Table 4 EC of isopropanolamine compounds containing adamantane on plant pathogenic bacteria 50

[0059]

[0060] “NT” represents not tested, “TC” represents a commercially available drug, and “KSM” represents a commercially available drug.

[0061] As can be seen from Table 3 and Table 4, the target compounds showed good inhibitory activity against plant pathogenic bacteria (such as Xanthomonas oryzae pv. oryzae and Xanthomonas axonopodis pv. citri) in vitro. The compounds showed excellent inhibitory activity against Xanthomonas oryzae pv. oryzae (Xoo), with EC 50 values of 1.25-19.6 μg / mL; the EC 50 values of compounds 5, 8, 11 were 3.51, 1.25, 3.74 μg / mL, respectively, and they also showed excellent inhibitory activity against Xanthomonas axonopodis pv. citri (Xac), with EC 50 values of 3.00, 1.60, 3.65, 4.07, 3.94, 2.87 μg / mL, respectively; in addition, the results of in vitro anti-Xanthomnas citri pv. Mangiferaeindicae (Xcm) analysis showed that the compounds had relatively obvious inhibitory effect against Xanthomnas citri pv. Mangiferaeindicae, with EC 50 values in the range of 1.28-31.8 μg / mL, and in particular, compounds 5, 8, 9, 16, 17 had lower EC 50 values of 6.00, 1.28, 5.74, 9.94, 6.29 μg / mL, respectively; and can be used for preparing anti-plant pathogenic bacteria pesticides.

[0062] Pharmacological Example 2:

[0063] Based on the fact that compound 8 showed relatively good in vitro activity (EC 50 value of 1.25 μg / mL) against Xanthomonas oryzae pv. oryzae, the in vivo anti-Xanthomonas oryzae pv. oryzae biological activity of the compound was studied by the leaf clipping method. The specific method was as follows: sterile scissors were dipped in Xanthomonas oryzae pv. oryzae (OD 595The bacterial liquid with the optical density (OD) of 0.6-0.8 is inoculated on rice plants (rice variety: Fengyouxiang, cultivation time: 8 weeks), and each treatment has three repetitions. The protection activity is that 200 μg / mL of the liquid (compound 8, 8@β-CD, β-CD, and positive control drug thiodiazole copper (20% content preparation, TC), kasugamycin (98% active ingredient, KSM)) is uniformly sprayed on the rice leaves until liquid drops are formed, and an equal amount of DMSO aqueous solution without the agent is used as a control, and then the bacteria are inoculated after 24 hours; the treatment activity is that the bacteria are inoculated on the rice plants first, and then 200 μg / mL of the liquid is uniformly sprayed on the rice leaves after 24 hours. Finally, the treated samples are placed in an artificial climate chamber (temperature: 28°C, humidity: 90%) for cultivation for 14 days, the lesion length and total length of the rice leaves are recorded, and the corresponding prevention and control effect is obtained by the grading standard calculation method.

[0064] The grading standard is as follows: first, the diseased length and total length of each leaf are measured, and then the percentage of the diseased length and the total length is calculated. Secondly, the leaves are classified according to the following grading standard: 1st grade, the diseased length is less than 5% of the total length of the leaf; 3rd grade, the diseased length accounts for 6-10% of the total length; 5th grade, the diseased length accounts for 11-20% of the total length; 7th grade, the diseased length accounts for 21-50% of the total length; and 9th grade, the diseased length accounts for more than 50% of the total length. Wherein, β-CD represents β-cyclodextrin.

[0065] The calculation method of the disease index is as follows:

[0066] Disease index = ∑ (number of leaves of each grade × corresponding grade) / (total number of leaves × highest grade)

[0067] The calculation method of the disease index is as follows:

[0068] Disease index = ∑ (number of leaves of each grade × corresponding grade) / (total number of leaves × highest grade)

[0069] The technical scheme of the present application is assisted by the examples of the present application, but the implementation content is not limited thereto, and the experimental results of the target compound are shown in Table 5, Figure 1

[0070] Table 5 Prevention and control effect of compound 8, 8@β-CD, and β-CD on rice bacterial leaf blight

[0071]

[0072] ​From Table 5, it can be seen that β-CD has no control effect on rice bacterial leaf blight, compound 8 has good protective activity (43.78%) and therapeutic activity (39.55%), but the activity is lower than that of the supramolecular binary complex 8@β-CD (protective and therapeutic activities are 51.06% and 46.49%, respectively) at the same concentration, and the protective and therapeutic activities of them are slightly better than those of the positive control drugs TC and CMM.

[0073] Pharmacological Example 3:

[0074] Based on the fact that compound 8 shows the best activity (EC 50 1.60 μg / mL) against X. axonopodis, a pot experiment in vivo was carried out on compound 8 against X. axonopodis, and the specific experimental steps are as follows:

[0075] Protective activity: Select citrus plants with uniform leaf growth, prick the leaves with a needle, and add 200 μg / mL of drug (compound 8, 8@β-CD, β-CD) adsorbed with filter paper to the wound site, with DMSO and water as negative controls, and TC as a positive control. Dry the leaves naturally after adding the drug, and then place them in an incubator with light conditions at 25°C for 24 h. Then inoculate with X. axonopodis bacterial solution with OD 595 = 0.01, and place it in an incubator with dark conditions at 20°C for 24 h. Finally, change the incubator conditions to a day-night exchange mode (day: 10-15 h, 10-15°C, humidity greater than 80%; night: 10-15 h, 10-15°C, humidity greater than 80%).

[0076] The control effect calculation method is as follows:

[0077] Control effect (%) = (chlorophyll content of water treatment group - chlorophyll content) / (chlorophyll content of water treatment group - chlorophyll content of CK treatment group) x 100

[0078] Therapeutic activity: prick the leaves of citrus with X. axonopodis bacterial solution with OD 595 = 0.05-0.1, and then place the dried leaves in an incubator with dark conditions at 20-25°C for 24 h. Then add 200 μg / mL of drug (compound 8, 8@β-CD, β-CD) to the filter paper to adhere to the leaves, with DMSO and water as negative controls, and TC as a positive control. Place it in an incubator with light conditions at 10-20°C for 24 h. Finally, change the incubator conditions to a day-night exchange mode (day: 10-15 h, 25°C, humidity greater than 80%; night: 10-15 h, 20°C, humidity greater than 80%). The control efficiency calculation method is the same as above.

[0079] The embodiment of the present application is assisted to illustrate the technical scheme of the present application, but the content of the embodiment is not limited thereto. The experimental results of the target compound are shown in Table 6.

[0080] Table 6 Protective and therapeutic activities of compound 8 and 8@β-CD on citrus canker

[0081]

[0082] As can be seen from Table 6, in the living body test, the target compound 8 at a concentration of 200 μg / mL showed good protective activity (45.29%) and therapeutic activity (54.61%) against Xanthomonas campestris, which were lower than those of the supramolecular binary compound 8@β-CD (protective activity and therapeutic activity were 73.22% and 67.13%, respectively), and both were better than the control drug (protective activity 37.37%; therapeutic activity 38.95%); it is indicated that the series of compounds can be used for preparing an agricultural pesticide against plant pathogenic bacteria.

Claims

1. A compound containing adamantane isopropanolamine or a salt thereof, characterized in that... The compound has a structure as shown in general formula (I): R1 and R2 are independently selected from hydrogen, methyl, ethyl, propyl, benzyl, o-methylbenzyl, m-methylbenzyl, p-methylbenzyl, o-tert-butylbenzyl, m-tert-butylbenzyl, p-tert-butylbenzyl, o-fluorobenzyl, m-fluorobenzyl, p-fluorobenzyl, o-trifluoromethylbenzyl, m-trifluoromethylbenzyl, p-trifluoromethylbenzyl, dichlorobenzyl, o-methoxybenzyl, m-methoxybenzyl, p-methoxybenzyl, and dimethoxybenzyl; when R1 and R2 form a ring, they are tetrahydropyrrole and piperazine.

2. The adamantane-containing isopropanolamine compound or its salt according to claim 1, characterized in that... Selected from the following compounds:

3. An intermediate compound for preparing the adamantane isopropanolamine compound or its salt as described in claim 1, characterized in that... As shown below:

4. The method for preparing the adamantane-containing isopropanolamine compound or its salt as described in claim 1 or 2, characterized in that... Includes the following steps: R1 and R2 are as described in claim 1.

5. A composition, characterized in that... The composition contains the compound or salt thereof as described in claim 1 or 2, and agriculturally available adjuvants or fungicides, insecticides or herbicides; the dosage form of the composition is selected from emulsifiable concentrates, powders, granules, aqueous solutions, suspensions, ultra-low volume sprays, microcapsules, fumigants, and water-in-oil emulsions.

6. Use of the compound of claim 1 or 2 or its salt or the composition of claim 5 in the prevention and control of agricultural pests and diseases, wherein the agricultural pests and diseases are rice bacterial blight fungus or mango angular leaf spot fungus.

7. A method for preventing and controlling agricultural pests and diseases, characterized in that: The compound or its salt as described in claim 1 or 2, or the composition as described in claim 5, is applied to a harmful substance or its living environment; the harmful substance is rice bacterial blight fungus or mango angular leaf spot fungus.

8. A method for protecting plants from agricultural pests and diseases, comprising the step of contacting the plant with the compound of claim 1 or 2 or a salt thereof, or the composition of claim 5.

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