Cinchonine derivative for preventing and treating agricultural diseases as well as preparation method and application thereof

Abstract

The invention discloses a cinchona alkaloid derivative for preventing and treating agricultural diseases as well as a preparation method and application thereof. The cinchona alkaloid derivative comprises a compound with a structural formula as shown in formula I, or pharmaceutically acceptable salt, solvate and tautomer thereof. It is found that the cinchona alkaloid derivative has an excellent inhibition effect on Xanthomonas oryzae pv. Oryzae and Xanthomonas citri pv. Citri, has great development value in the aspect of treating plant pathogenic bacteria, and provides more choices for agricultural disease control.

Description

Technical Field

[0001] The invention relates to the technical field of pesticides, and in particular to a cinchona alkaloid derivative for preventing and controlling agricultural diseases, and a preparation method and application thereof. Background Art

[0002] Plant bacterial diseases are the most difficult problems to control during the growth of crops. They not only cause large-scale crop damage, but also cause serious economic losses. For example, rice bacterial blight can reduce rice yields by 20% to 50%, while citrus canker poses a huge threat to major citrus fruits worldwide. Since the 1960s, chemical pesticides have become one of the main means of controlling pests. However, with the long-term and widespread use of chemical fungicides, plant pathogenic bacteria have gradually developed resistance to these drugs, which not only increases the difficulty of control, but also poses a serious threat to human health and environmental safety. Therefore, the development of new prevention and control strategies and alternative agents is urgent.

[0003] Quinine, also known as cinchona alkaloids, is an alkaloid extracted from the bark of the cinchona tree and its congeners in the Rubiaceae family. Studies have shown that the bark of the cinchona tree is particularly rich in alkaloids, and the quinine content in the dry bark can be as high as 70%. This type of alkaloids also includes components such as hydroquinine, quinidine, cinchonine and hydroquinidine. These compounds all contain chiral 1-bicyclo[2.2.2] nitrogen-containing octane and quinoline ring structures, which can provide a natural chiral environment and show excellent stereoselectivity in asymmetric catalytic reactions. At present, research on this type of alkaloids and their derivatives mainly focuses on antimalarial treatment. However, there are few reports on their application in the prevention and control of agricultural bacterial diseases.

[0004]

[0005] The inventors tried to use quinine, hydroquinine, quinidine, cinchonis and hydroquinidine to control rice bacterial blight and citrus canker, but the effect was not outstanding. It is of great research value whether more new compounds with good inhibition rates on both rice bacterial blight and citrus canker can be obtained through structural optimization. Summary of the invention

[0006] Purpose of the Invention

[0007] In order to overcome the above shortcomings, the purpose of the present invention is to provide a cinchona alkaloid derivative for preventing and controlling agricultural diseases, as well as a preparation method and application thereof. The cinchona alkaloid derivative of the present invention exhibits a potential inhibitory effect on two types of agricultural bacteria, namely, rice bacterial blight pathogen and citrus canker pathogen, and is significantly superior to the control drugs thiophanate-methyl and thiophanate-copper, and is expected to be developed into a new type of agricultural drug for resisting plant pathogenic bacteria.

[0008] Solution

[0009] To achieve the purpose of the present invention, the technical solution adopted by the present invention is as follows:

[0010] In a first aspect, the present invention provides a cinchona alkaloid derivative for preventing and controlling agricultural diseases, which includes a compound having a structural formula as shown in Formula I, or a pharmaceutically acceptable salt, a solvate and a tautomer thereof;

[0011]

[0012] Wherein, in Formula I, R1 is any of the following groups:

[0013] R2 is one of substituted phenyl and C3-C10 alkyl; substituted phenyl includes halogenated phenyl, halogenated alkyl substituted phenyl, oxyalkyl substituted phenyl, cyanophenyl or C1-C5 alkyl substituted phenyl.

[0014] Optionally, R1 is

[0015] Optionally, R2 includes halogenated phenyl, trifluoromethyl substituted phenyl or tert-butyl substituted phenyl; optionally R2 includes iodinated phenyl, fluorophenyl, chlorophenyl, trifluoromethyl substituted phenyl or tert-butyl substituted phenyl; R2 includes p-iodophenyl, p-fluorophenyl, p-chlorophenyl, p-trifluoromethylphenyl or p-tert-butylphenyl.

[0016] Optionally, it includes at least one of the compounds having the structural formula shown in any one of Formulas K1 to K4, K6 to K15, or a pharmaceutically acceptable salt, solvate or tautomer thereof:

[0017]

[0018]

[0019] Optionally, at least one of the compounds represented by any one of the structural formulae K2 to K4, K6, K7, K9 to K11, or a pharmaceutically acceptable salt, solvate or tautomer thereof is selected.

[0020] Optionally, it is selected from at least one of the compounds having structural formulae K2, K6, K9 to K11, or a pharmaceutically acceptable salt, solvate or tautomer thereof;

[0021]

[0022] Optionally, it is selected from at least one of the compounds having structural formulae K2, K10, and K11, or a pharmaceutically acceptable salt, solvate, and tautomer thereof:

[0023]

[0024] In a second aspect, a method for preparing the cinchona alkaloid derivatives described in the first aspect is provided, comprising: dissolving quinine alkaloids and amines in an organic solvent, adding an acyl chloride compound, stirring the reaction, and purifying to obtain the cinchona alkaloid derivatives;

[0025] The quinine alkaloid is selected from one or more of quinine sulfate, hydroquinine, quinidine, cinchonine and hydroquinidine;

[0026] The acyl chloride compound is selected from one or more of 4-chlorobenzoyl chloride, 4-trifluoromethylbenzoyl chloride, p-methoxybenzoyl chloride, p-cyanobenzoyl chloride, p-fluorobenzoyl chloride, p-iodobenzoyl chloride, p-tert-butylbenzoyl chloride, n-butyryl chloride, n-valeryl chloride, hexanoyl chloride and isobutyryl chloride;

[0027] Optionally, the amine is triethylamine;

[0028] Optionally, the organic solvent is a chlorinated alkane, optionally dichloromethane.

[0029] In a third aspect, a pesticide preparation is provided, wherein the active ingredient comprises the cinchona alkaloid derivative described in the first aspect or the cinchona alkaloid derivative prepared by the preparation method described in the second aspect;

[0030] Optionally, it also includes an agriculturally acceptable carrier;

[0031] Optionally, the weight percentage of the cinchona alkaloid derivative in the medicament is 1 to 99%;

[0032] Optionally, the pesticide preparation is in the form of a suspension concentrate, a dry suspension concentrate, an oil suspension concentrate, a wettable powder or a water dispersible granule;

[0033] Optionally, the pesticide formulation is used to prevent and control rice bacterial blight and / or citrus canker.

[0034] In a fourth aspect, a use of a cinchona alkaloid derivative in preventing and controlling agricultural diseases is provided, wherein the cinchona alkaloid derivative includes a compound having a structural formula as shown in Formula I, or a pharmaceutically acceptable salt thereof, a solvate thereof, and a tautomer thereof;

[0035]

[0036] Wherein, in Formula I, R1 is any of the following groups:

[0037] R2 is one of substituted phenyl and C3-C10 alkyl; substituted phenyl includes halogenated phenyl, halogenated alkyl substituted phenyl, oxyalkyl substituted phenyl, cyanophenyl or C1-C5 alkyl substituted phenyl.

[0038] Optionally, R1 is

[0039] Optionally, R2 includes halogenated phenyl, trifluoromethyl substituted phenyl or tert-butyl substituted phenyl; optionally R2 includes iodinated phenyl, fluorophenyl, chlorophenyl, trifluoromethyl substituted phenyl or tert-butyl substituted phenyl; R2 includes p-iodophenyl, p-fluorophenyl, p-chlorophenyl, p-trifluoromethylphenyl or p-tert-butylphenyl.

[0040] Optionally, it includes at least one of the compounds having a structural formula as shown in any one of Formulas K1 to K15, or a pharmaceutically acceptable salt, a solvate, and a tautomer thereof:

[0041]

[0042]

[0043] Optionally, at least one compound selected from any one of the compounds having structural formulae K2 to K6, K7, K9 to K11, or a pharmaceutically acceptable salt, solvate or tautomer thereof;

[0044] Optionally, it is selected from at least one of the compounds having structural formulae K2, K5, K6, K9 to K11, or a pharmaceutically acceptable salt, solvate or tautomer thereof;

[0045]

[0046] Optionally, it is selected from at least one of the compounds having structural formulae K2, K10, and K11, or a pharmaceutically acceptable salt, solvate, and tautomer thereof:

[0047]

[0048] Optionally, the plant bacterial disease is one or more of rice bacterial blight and citrus canker.

[0049] Beneficial Effects

[0050] (1) The present invention found that cinchona alkaloid derivatives showed excellent inhibitory effects on rice bacterial blight and citrus canker, and have great development value in the treatment of plant pathogenic bacteria, providing more options for agricultural disease prevention and control.

[0051] (2) The cinchona alkaloid derivative of the present invention can be obtained by a one-step esterification reaction, with a short synthesis step, and has the characteristics of easy synthesis, simple structure, green and high efficiency, etc. It is worthy of further research and development as a lead compound in the prevention and treatment of agricultural bacterial pathogens. DETAILED DESCRIPTION

[0052] In order to make the purpose, technical solution and advantages of the embodiments of the present invention clearer, the technical solution in the embodiments of the present invention will be described clearly and completely below. Obviously, the described embodiments are part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0053] In addition, in order to better illustrate the present invention, numerous specific details are provided in the specific embodiments below. It should be understood by those skilled in the art that the present invention can be implemented without certain specific details. In some embodiments, raw materials, schemes, methods, means, etc. well known to those skilled in the art are not described in detail, so as to highlight the main purpose of the present invention.

[0054] Unless explicitly stated otherwise, throughout the specification and claims, the term “comprise” or variations such as “include” or “comprising”, etc., will be understood to include the stated elements or components but not to exclude other elements or components.

[0055] The cinchona alkaloid derivative of the present invention is a derivative obtained by introducing an ester group on the basis of cinchona alkaloid, and the pure product is separated by conventional methods such as silica gel column chromatography, and the structure of the cinchona alkaloid derivative is identified by nuclear magnetic resonance spectroscopy, mass spectrometry and other technologies. The activity screening results show that the cinchona alkaloid derivative has a good inhibitory effect on rice bacterial blight and citrus canker.

[0056] The experimental methods in the examples of the present invention without specifying specific conditions are usually carried out under conventional conditions or under conditions recommended by raw material or commodity manufacturers. Reagents without specifying specific sources are conventional reagents purchased from the market.

[0057] 1. Synthesis Example

[0058] Compounds K1-K4 and K6-K15 were prepared by esterification reaction of quinine derivatives with differently substituted acyl chlorides, respectively. Compound K5 (hydroquinoline 4-chlorobenzoate, CAS No. 113162-02-0) was purchased from Anage Chemical Reagent Company.

[0059] Example 1 Synthesis of Compound K1:

[0060] Dissolve quinine sulfate (0.78 mmol) and triethylamine (1.15 mmol) in dichloromethane (10 mL), add 4-chlorobenzoyl chloride (1.04 mmol) dropwise at 0°C, and stir the reaction solution at room temperature for 3 hours. Quench the reaction with saturated sodium bicarbonate aqueous solution, extract with dichloromethane, wash with water, dry, concentrate, and purify by silica gel column chromatography to obtain a white solid named K1. K1 yield: 82%; white solid; K1 NMR data are as follows:

[0061] 1 H NMR(400MHz,Chloroform-d)δ8.73(d,J=4.5Hz,1H),8.05–7.99(m,3H),7.50(d,J=2.7Hz,1H),7.45(d,J=8.3Hz,2H), 7.40(d,J=4.6Hz,1H),7.39–7.36(m,1H),6.73(d,J=6.8Hz,1H),5.85(ddd,J=17.4,10.4,7.4Hz,1H),5.10–4.98(m,2 H),3.98(s,3H),3.50(q,J=7.9Hz,1H),3.18(dq,J=14.4,6.5Hz,1H),3.09(dd,J=13.8,10.0Hz,1H),2.77–2.62(m,2H ),2.32(d,J=11.3Hz,1H),2.03–1.85(m,2H),1.73(dtd,J=31.1,12.8,12.3,5.7Hz,2H),1.58(q,J=10.9,9.9Hz,1H). 13 C NMR(101MHz,Chloroform-d)δ164.79,158.05,147.48,144.84,141.66,140.05,131.94,131.03(2C),129.04(2C),128.17 ,126.93,121.94,118.67,114.67,101.36,74.71,59.40,56.72,55.70,42.59,39.67,29.72,27.91,27.60,24.30.MS-ESI m / z:463.1892[M+H] + .

[0062] Example 2 Synthesis of Compound K2

[0063] The operation method is as in Example 1, except that hydrogenated quinine is substituted for quinine sulfate to prepare compound K2 (which has the same cis-trans structure as K5).

[0064] K2: Yield: 83%; white solid; K2 NMR data are as follows:

[0065] 1 H NMR(400MHz,Chloroform-d)δ8.70(d,J=4.5Hz,1H),8.05–8.01(m,3H),7.55(d,J=2.7Hz,1H),7.50 –7.44(m,2H),7.41–7.35(m,2H),6.95(s,1H),4.00(s,3H),3.50(td,J=8.7,4.9Hz,1H),3.32(s,1H) ,3.22(dd,J=13.6,10.1Hz,1H),2.88–2.78(m,1H),2.51(d,J=13.8Hz,1H),1.96(q,J=3.2Hz,1H),1 .86(s,3H),1.61(d,J=14.9Hz,2H),1.34(td,J=7.6,1.7Hz,1H),1.25(s,1H),0.86(t,J=7.3Hz,3H). 13 C NMR(101MHz,Chloroform-d)δ164.30,158.46,147.25,144.79,140.23,131.89,131.07,130.99(2C),129.15(2C), 128.10,128.03,126.61,122.39,118.09,101.15,58.96,57.98,56.09,42.77,36.83,27.59,25.20,11.97.MS-ESI m / z:465.2082[M+H] + .

[0066] Example 3 Synthesis of Compound K3

[0067] The operation method is as in Example 1, except that quinidine is used instead of quinine sulfate to prepare compound K3.

[0068] K3: yield: 80%; white solid; K3 NMR data are as follows:

[0069] 1H NMR(400MHz,Chloroform-d)δ8.71(d,J=4.6Hz,1H),8.02(dd,J=8.9,5.1Hz,3H),7.49(d,J=2.7Hz,1H),7 .46–7.42(m,2H),7.38(dt,J=5.4,2.3Hz,2H),6.80(d,J=6.6Hz,1H),6.01(ddd,J=17.2,10.4,6.7Hz,1H), 5.17–5.04(m,2H),3.98(s,3H),3.43(td,J=9.0,6.5Hz,1H),2.95(dd,J=44.5,7.8Hz,3H),2.78(dt,J=13 .4,8.7Hz,1H),2.32(q,J=8.3Hz,1H),2.01(dd,J=13.4,9.1Hz,1H),1.91–1.87(m,1H),1.64–1.57(m,3H). 13 C NMR(101MHz,Chloroform-d)δ164.48,157.91,147.22,144.56,143.30,139.80(d,J=10.7Hz),131.69,130.95(2C),128.77(2C) ,127.90,126.73,121.87,118.18,114.93,101.08,74.02,59.10,55.52,49.62,49.00,39.11,27.39,25.99,23.22,0.84.MS-ESI m / z:463.1922[M+H] + .

[0070] Example 4 Synthesis of Compound K4

[0071] The operation method is as in Example 1, except that cinchonine is used instead of quinine sulfate to prepare compound K4.

[0072] K4: Yield: 82%; white solid; K4 NMR data are as follows:

[0073] 1H NMR(400MHz,Chloroform-d)δ8.88(d,J=4.5Hz,1H),8.30(dd,J=8.5,1.4Hz,1H),8.14(dd,J=8.5,1.3Hz,1H),8 .05–7.98(m,2H),7.63(ddd,J=8.3,6.8,1.3Hz,1H),7.47–7.42(m,3H),6.79(d,J=6.9Hz,1H),5.84(ddd,J=17.4 ,10.4,7.4Hz,1H),5.15–4.91(m,2H),3.56–3.45(m,1H),3.19(dddd,J=13.1,10.2,5.4,2.4Hz,1H),3.07(dd,J= 13.9,10.0Hz,1H),2.74–2.59(m,2H),2.48–2.14(m,2H),1.94(ddp,J=20.0,9.8,3.4Hz,2H),1.83–1.54(m,3H). 13 C NMR(101MHz,Chloroform-d)δ164.53,149.79,148.45,144.88,141.37,139.84,130.85,130.38(2C),129.12,128.83(2C),127.9 3,126.86,125.70,123.04,118.30,114.51,74.66,59.67,56.51,42.31,39.41,27.63,27.41,24.20.MS-ESIm / z:433.1812[M+H] + .

[0074] Example 5 Synthesis of Compound K6

[0075] The operation was carried out in accordance with Example 1, except that quinine sulfate was replaced by hydroquinidine and 4-trifluoromethylbenzoyl chloride was replaced by 4-chlorobenzoyl chloride to prepare compound K6.

[0076] K6: Yield: 80%; white solid; K6 NMR data are as follows:

[0077] 1H NMR(400MHz,Chloroform-d)δ8.73(d,J=4.5Hz,1H),8.20(d,J=8.1Hz,2H),8.02(d,J=9.2Hz,1H),7.74(d,J=8.2Hz, 2H),7.50(d,J=2.7Hz,1H),7.41(d,J=4.5Hz,1H),7.38(dd,J=9.3,2.7Hz,1H),6.80(d,J=7.2Hz,1H),3.99(s,3H),3 .45(q,J=8.5Hz,1H),2.95(dd,J=13.9,8.1Hz,1H),2.85(t,J=11.6Hz,1H),2.74(dt,J=13.1,8.4Hz,2H),1.90(t,J= 11.2Hz, 1H), 1.78 (d, J = 4.7Hz, 1H), 1.60 (dd, J = 9.0, 4.8Hz, 1H), 1.50 (dt, J = 10.9, 4.9Hz, 3H), 0.91 (t, J = 6.9Hz, 3H). 13 C NMR(101MHz,Chloroform-d)δ163.45,157.05,146.41,143.77,142.38,134.06,133.74,131.95,130.89,129.05(2C),126.01,124.63 (d,J=3.9Hz),123.84,120.97,117.54,100.32,73.62,58.42,54.64,49.79,48.91,36.24,26.01,25.05,24.42,22.52,10.87.MS-ESI m / z:499.2312[M+H] + .

[0078] Example 6 Synthesis of Compound K7

[0079] The operation method was similar to that of Example 1, except that hydroquinidine was used instead of quinine sulfate, and p-methoxybenzoyl chloride was used instead of 4-chlorobenzoyl chloride to prepare compound K7.

[0080] K7: Yield: 81%; white solid; K7 NMR data are as follows:

[0081] 1H NMR(400MHz,Chloroform-d)δ8.69(d,J=4.5Hz,1H),8.09–8.03(m,2H),8.03–7.99(m,1 H),7.59(d,J=2.7Hz,1H),7.42–7.34(m,2H),7.05(s,1H),6.99–6.92(m,2H),4.01(s,3H ),3.85(d,J=13.6Hz,3H),3.44(td,J=9.2,5.0Hz,1H),3.12–2.85(m,4H),2.14(t,J=11. 4Hz,1H),1.87–1.83(m,1H),1.59(ddt,J=27.8,24.8,8.4Hz,6H),0.92(t,J=7.1Hz,3H). 13 C NMR(101MHz,Chloroform-d)δ164.75,163.87,158.41,147.22,144.71,143.17,131.74(2C),131.55,126.69,122.47,121.91 ,118.07,113.94(2C),113.12,101.18,72.71,59.05,56.14,55.55,55.32,50.27,49.65,36.68,26.09,25.26,11.75.MS-ESI m / z:461.2535[M+H] + .

[0082] Example 7 Synthesis of Compound K8

[0083] The operation method was similar to that of Example 1, except that hydroquinidine was used instead of quinine sulfate, and p-cyanobenzoyl chloride was used instead of 4-chlorobenzoyl chloride to prepare compound K8.

[0084] K8: Yield: 79%; white solid; K8 NMR data are as follows:

[0085] 1H NMR(400MHz,Chloroform-d)δ8.73(d,J=4.6Hz,1H),8.21–8.14(m,2H),8.02(d,J= 9.2Hz,1H),7.80–7.74(m,2H),7.49(d,J=2.7Hz,1H),7.38(dd,J=9.1,3.3Hz,2H), 6.81(d,J=6.9Hz,1H),3.98(s,3H),3.45(q,J=8.6Hz,1H),2.98–2.67(m,4H),1.89 (t,J=11.2Hz,1H),1.78(d,J=4.5Hz,1H),1.69–1.42(m,6H),0.90(t,J=7.0Hz,3H). 13 C NMR(101MHz,Chloroform-d)δ164.50,158.57,147.85,145.23,143.61,133.97,132.87(2C),132.38,130.58(2C),127.4 5,122.46,118.20,117.35,101.76,75.19,59.86,56.14,51.23,50.33,37.63,27.39,26.48,25.90,24.00,12.33.MS-ESI m / z:456.2381[M+H] + .

[0086] Example 8 Synthesis of Compound K9

[0087] The operation method was similar to that of Example 1, except that hydroquinidine was used instead of quinine sulfate, and p-fluorobenzoyl chloride was used instead of 4-chlorobenzoyl chloride to prepare compound K9.

[0088] K9: Yield: 83%; white solid; K9 NMR data are as follows:

[0089] 1H NMR(400MHz,Chloroform-d)δ8.72(d,J=4.5Hz,1H),8.15–8.07(m,2H),8.01(d,J=9.2Hz,1H), 7.51(d,J=2.7Hz,1H),7.43–7.34(m,2H),7.14(t,J=8.6Hz,2H),6.82(d,J=6.8Hz,1H),3.99(s ,3H),3.43(q,J=8.5Hz,1H),2.97(dd,J=14.4,7.7Hz,1H),2.87(t,J=11.5Hz,1H),2.82–2.70( m,2H),1.94(t,J=11.2Hz,1H),1.78(d,J=4.6Hz,1H),1.66–1.44(m,6H),0.90(t,J=6.9Hz,3H). 13 C NMR(101MHz,Chloroform-d)δ167.75,165.12(d,J=20.1Hz),158.53,147.85,145.22,144.02,132.68(d,J=9.4Hz,2C),132.30,127.45,126.4 3(d,J=2.9Hz),122.51,118.93,116.39,116.17,101.80,74.45,59.87, 56.19,51.17,50.35,37.63,27.36,26.56,25.86,23.77,12.31.MS-ESI m / z:449.2329[M+H] + .

[0090] Example 9 Synthesis of Compound K10

[0091] The operation method was similar to that of Example 1, except that hydroquinidine was used instead of quinine sulfate, and p-iodobenzoyl chloride was used instead of 4-chlorobenzoyl chloride to prepare compound K10.

[0092] K10: Yield: 80%; white solid; K10 NMR data are as follows:

[0093] 1H NMR(400MHz,Chloroform-d)δ8.72(d,J=4.5Hz,1H),8.01(d,J=9.2Hz,1H),7.86–7.75(m ,4H),7.49(d,J=2.7Hz,1H),7.42–7.33(m,2H),6.76(d,J=7.0Hz,1H),3.98(s,3H),3.41( q,J=8.5Hz,1H),2.94(dd,J=14.2,8.0Hz,1H),2.89–2.79(m,1H),2.74(dt,J=13.6,8.6Hz ,2H),1.94–1.84(m,1H),1.76(d,J=4.6Hz,1H),1.65–1.41(m,6H),0.90(t,J=7.0Hz,3H). 13 C NMR(101MHz,Chloroform-d)δ165.29,158.15,147.56,144.91,143.70,138.11(2C),132.00,131.15(2C),129.34,127. 15,122.12,118.68,101.49(2C),74.47,59.55,55.80,50.92,50.07,37.40,27.17,26.22,25.56,23.59,12.04.MS-ESI m / z:557.1329[M+H] + .

[0094] Example 10 Synthesis of Compound K11

[0095] The operation method was similar to that of Example 1, except that quinine sulfate was replaced by hydroquinidine and 4-chlorobenzoyl chloride was replaced by p-tert-butylbenzoyl chloride to prepare compound K11.

[0096] K11: Yield: 81%; white solid; K11 NMR data are as follows:

[0097] 1H NMR(400MHz,Chloroform-d)δ8.71(d,J=4.6Hz,1H),8.07–7.97(m,3H),7.52(d,J=2.7H z,1H),7.42(d,J=4.6Hz,1H),7.36(dd,J=9.2,2.7Hz,1H),6.77(d,J=7.0Hz,1H),3.98( s,3H),3.42(q,J=8.5Hz,1H),2.94(dd,J=13.7,8.7Hz,1H),2.89–2.68(m,3H),1.98–1. 88(m,1H),1.75(d,J=4.7Hz,1H),1.66–1.44(m,6H),1.34(s,9H),0.90(t,J=7.1Hz,3H). 13 C NMR(101MHz,Chloroform-d)δ165.40,157.74,157.03,147.25,144.57,143.83,131.60,129.39(2C),126.90,126.77,125.37(2C) ,121.76,118.45,101.24,73.70,59.28,55.46,50.59,49.77,37.16,34.96,30.89(3C),26.92,25.96,25.21,23.28,11.73.MS-ESI m / z:487.2994[M+H] + .

[0098] Example 11 Synthesis of Compound K12

[0099] The operation method was similar to that of Example 1, except that quinine sulfate was replaced by hydroquinidine and 4-chlorobenzoyl chloride was replaced by n-butyryl chloride to prepare compound K12.

[0100] K12: Yield: 80%; white solid; K12 NMR data are as follows:

[0101] 1H NMR(400MHz,Chloroform-d)δ8.71(d,J=4.5Hz,1H),8.00(d,J=9.2Hz,1H),7.44(d,J=2.7Hz,1H),7.3 6(dd,J=9.3,2.7Hz,1H),7.31(d,J=4.5Hz,1H),6.61(d,J=6.4Hz,1H),3.96(s,3H),3.26(td,J=8.9,6 .2Hz,1H),2.94(dd,J=13.7,8.3Hz,1H),2.86–2.68(m,3H),2.37(t,J=7.4Hz,2H),1.88–1.79(m,1H), 1.75 (s, 1H), 1.67 (h, J = 7.4Hz, 2H), 1.49 (dtt, J = 23.4, 13.4, 4.0Hz, 5H), 0.92 (td, J = 7.2, 3.5Hz, 7H). 13 C NMR(101MHz,Chloroform-d)δ172.86,158.44,147.75,145.14,144.22,132.16,127.38,122.46,118.82,1 01.78,73.47,59.39,56.18,51.02,37.54,36.80,27.30,26.45,25.81,23.37,18.79,14.12,12.36.MS-ESI m / z:397.2539[M+H] + .

[0102] Example 12 Synthesis of Compound K13

[0103] The operation method was similar to that of Example 1, except that hydroquinidine was used instead of quinine sulfate, and n-valeryl chloride was used instead of 4-chlorobenzoyl chloride to prepare compound K13.

[0104] K13: Yield: 80%; white solid; K13 NMR data are as follows:

[0105] 1H NMR(400MHz,Chloroform-d)δ8.72(d,J=4.6Hz,1H),8.00(d,J=9.2Hz,1H),7.43(d,J=2.7Hz,1H),7.36 (dd,J=9.2,2.7Hz,1H),7.31(d,J=4.5Hz,1H),6.59(d,J=6.3Hz,1H),3.97(s,3H),3.26(td,J=8.9,6.1 Hz,1H),2.95(dd,J=13.8,8.5Hz,1H),2.88–2.66(m,3H),2.43–2.35(m,2H),1.89–1.79(m,1H),1.75(d ,J=4.8Hz,1H),1.67–1.60(m,2H),1.58–1.44(m,3H),1.44–1.24(m,3H),0.91(dt,J=11.0,7.2Hz,6H). 13 C NMR(101MHz,Chloroform-d)δ173.05,158.48,147.76,145.14,144.27,132.17,127.38,122.49,118.82,101.78,73.56, 59.32,56.18,51.01,50.21,37.59,34.68,28.00,27.35(d,J=3.0Hz),26.51,25.86,23.32,22.70,14.12,12.41.MS-ESI m / z:411.2694[M+H] + .

[0106] Example 13 Synthesis of Compound K14

[0107] The operation method was similar to that of Example 1, except that quinine sulfate was replaced by hydroquinidine and 4-chlorobenzoyl chloride was replaced by hexanoyl chloride to prepare compound K14.

[0108] K14: Yield: 81%; white solid; K14 NMR data are as follows:

[0109] 1H NMR(400MHz,Chloroform-d)δ8.71(d,J=4.5Hz,1H),8.00(d,J=9.2Hz,1H),7.43(d,J=2.7Hz,1H),7.36(dd ,J=9.2,2.7Hz,1H),7.31(d,J=4.5Hz,1H),6.60(d,J=6.6Hz,1H),3.97(s,3H),3.27(td,J=8.9,6.2Hz,1H) ,2.94(dd,J=13.8,8.3Hz,1H),2.86–2.68(m,3H),2.38(dd,J=8.1,7.0Hz,2H),1.88–1.80(m,1H),1.76(s, 1H),1.69–1.59(m,2H),1.59–1.37(m,5H),1.27(qd,J=7.9,7.0,4.4Hz,5H),0.89(dt,J=25.6,7.1Hz,6H). 13 CNMR(101MHz,Chloroform-d)δ172.75,158.13,147.46,144.86,143.91,127.09,122.14,118.56,101.49,73. 21,59.17,55.88,50.80,50.02,37.27,34.59,31.38,27.02,25.53,24.68,23.12,22.39,13.98,12.07.MS-ESI m / z:425.2852[M+H] + .

[0110] Example 14 Synthesis of Compound K15

[0111] The operation method was similar to that of Example 1, except that hydroquinidine was used instead of quinine sulfate, and isobutyryl chloride was used instead of 4-chlorobenzoyl chloride to prepare compound K15.

[0112] K15: Yield: 80%; white solid; K15 NMR data are as follows:

[0113] 1H NMR(400MHz,Chloroform-d)δ8.71(d,J=4.6Hz,1H),8.00(d,J=9.2Hz,1H),7.42(d,J=2.7Hz,1H),7.36(dd,J=9 .2,2.7Hz,1H),7.31(d,J=4.5Hz,1H),6.54(d,J=6.8Hz,1H),3.96(s,3H),3.69(q,J=7.0Hz,1H),3.31–3.24(m, 1H),2.93(dd,J=13.8,8.4Hz,1H),2.80(ddt,J=12.5,9.6,2.7Hz,1H),2.75–2.66(m,2H),2.65–2.56(m,1H),1. 84–1.76(m,1H),1.74(d,J=4.7Hz,1H),1.61–1.40(m,6H),1.19(dd,J=12.6,7.0Hz,7H),0.91(t,J=7.1Hz,3H). 13 C NMR(101MHz,Chloroform-d)δ175.98,158.09,147.44,144.81,144.15,131.81,127.15,122.14,118.51,101.46,73. 28,59.18,55.78,50.71,49.86,37.35,34.34,27.08,26.23,25.50,23.29,18.99(d,J=4.0Hz),18.56,12.08.MS-ESI m / z:397.2538[M+H] + .

[0114] Test Example 1: Determination of the activity of cinchona alkaloid derivatives against agricultural pathogenic bacteria and its results

[0115] 1) Test agents: cinchona alkaloid derivatives K1 to K15.

[0116] 2) Test strains: Xanthomonas oryzae ACCC 11602, the pathogen of rice bacterial blight, and Xanthomonas axonopodis pv. Citri, the pathogen of citrus canker, were provided by Guangxi Tianyuan Biochemical Co., Ltd. They are common pathogens of rice bacterial blight or citrus canker. Other strains may also be used.

[0117] 3) Antimicrobial activity test:

[0118] The strain used in this experiment is a strain frozen at -80℃ in the laboratory with 30% glycerol. Take out the frozen strain, streak it on NA solid culture medium (beef extract: 3g, peptone: 5g, yeast powder: 1g, sucrose: 10g, agar: 15g, distilled water: 1L, pH7.0; sterilize at 121℃ for 20min), and culture it at a constant temperature of 28℃ until a single colony grows. Pick up the single colonies on the solid culture medium and transfer them to NB liquid culture medium (beef extract: 3g, peptone: 5g, yeast powder: 1g, sucrose: 10g, distilled water: 1L; sterilize at 121℃ for 20min), and culture it on a constant temperature shaker at 28℃ and 180rpm until it reaches the logarithmic growth phase. Dilute the strain in the logarithmic growth phase to about 10 with NB liquid culture medium. 6 Dissolve compounds K1 to K15 in DMSO, add them to the liquid culture medium, mix them evenly, and prepare a drug-containing liquid culture medium with a concentration of 200 μg / mL. Take 50 μL of the drug-containing culture medium and the same volume of the drug-containing medium containing about 10 6 CFU / mL bacterial culture was added to the wells of a 96-well plate, and the final drug concentration was 100μg / mL. 100μL of bacterial solution of the same concentration containing an equal amount of DMSO was used as a control. The 96-well plate was cultured in a 28°C constant temperature incubator for 24-48h until the bacterial solution in the control group became turbid, and the OD value (OD 600 ). In addition, the OD values ​​of 100 μL of liquid culture medium and the drug with a concentration of 100 μg / mL were measured to correct the OD values ​​caused by the culture medium and the drug itself. The calculation formula for the corrected OD value and inhibition rate is as follows:

[0119] Corrected OD value = OD value of bacterial culture medium - OD value of sterile culture;

[0120] Inhibition rate = (corrected control culture medium bacterial solution OD value - corrected drug-containing culture medium OD value) / corrected control culture medium bacterial solution OD value × 100%

[0121] All experiments were repeated three times, and the inhibition rates of the compounds were shown in Table 1.

[0122] Table 1 Inhibition rate of cinchona alkaloid derivatives on plant pathogenic bacteria at 100 μg / mL (%)

[0123]

[0124]

[0125] From the test results in Table 1, it can be seen that the cinchona alkaloid derivatives of the present invention exhibit good antibacterial activity against Xanthomonas oryzae and Xanthomonas citri odoratus, and some of the compounds exhibit high activity, especially K1 to K11. Compared with the parent compounds quinine, hydroquinine, quinidine, cinchonis and hydroquinidine, the antibacterial activity is significantly improved, especially against Xanthomonas citri odoratus.

[0126] The compound-containing liquid culture medium was diluted by two-fold dilution in a 96-well plate to obtain 50 μL of a series of concentrations of the drug-containing culture medium, and then the inhibition rate corresponding to the series of concentrations was determined according to the same test method as above. All experiments were set up in triplicate to determine the MIC of the compound. 90 The values ​​(the lowest drug concentration that inhibits 90% bacterial growth) are shown in Table 2.

[0127] Table 2 MIC90 (μg / mL) of cinchona alkaloid derivatives K1-K15 against plant pathogenic bacteria in vitro

[0128]

[0129]

[0130] From the activity test results in Table 2, it can be seen that the cinchona alkaloid derivatives K1 to K15 described in the present invention show different degrees of inhibitory activity against two plant pathogenic bacteria, among which K2, K10 and K11 have a minimum inhibitory concentration MIC90 value of 6.25 μg / mL against rice bacterial blight and citrus canker, and K5, K6 and K9 also have relatively good antibacterial activity; significantly better than the control drugs thiophanate-methyl and thiophanate-copper, and the antibacterial activity is significantly improved compared with the parent compound. The raw materials of this type of derivatives are easy to obtain and easy to synthesize. Among them, the antibacterial activity of hydrogenated quinidine aromatic ester compounds is significantly higher than that of the control drugs thiophanate-methyl and thiophanate-copper, avoiding the problem of complicated preparation process of other derivatives. This shows that these compounds have the value of further development and are expected to be developed into new agricultural antibacterial agents.

[0131] The preparation methods of the dosage forms in the following formulation examples of the present invention are as follows:

[0132] The preparation method of the suspension concentrate is as follows: weigh a wetting agent, a dispersant, an antifreeze agent, a preservative, a defoaming agent, and deionized water according to a ratio, add them into a beaker and mix them evenly, then add a cinchona alkaloid derivative into the beaker, and then transfer it to a sand mill, grind it in the sand mill for 2-3 hours, add a thickener and continue grinding for 0.5 hours, control the particle size D95 to be below 5 microns, and filter it to obtain the suspension concentrate.

[0133] The laboratory preparation method of the oil suspension is: weigh the dispersant, wetting agent, emulsifier, defoamer and solvent according to the ratio, add them into a beaker and mix them evenly, then add the cinchona alkaloid derivative into the beaker, and then transfer it to a sand mill and grind it for 2-3 hours, add the thickener and continue grinding for 0.5 hours, so that the particle size D95 is controlled below 5 microns, and filter it to obtain it.

[0134] The preparation method of the dry suspension is as follows: weigh the wetting agent, dispersant, filler and water according to the proportion, add them into a beaker and mix them evenly, then add the cinchona alkaloid derivative into the beaker, and then transfer it to a sand mill and grind it for 2-3 hours to make the particle size D 95 The particle size is controlled below 5 microns, filtered and the obtained material is dried by a spray dryer to obtain the product.

[0135] The preparation method of the wettable powder is as follows: weigh the cinchona alkaloid derivative, wetting agent, dispersant and filler according to the proportion, add them into a mixer and mix them evenly, and then put them into a jet mill to grind them to obtain the wettable powder.

[0136] The preparation method of water dispersible granules is as follows: cinchona alkaloid derivatives, wetting agents, dispersants, disintegrants, sustained-release agents and fillers are weighed according to the proportion, added into a mixer and mixed evenly, then put into a jet mill for pulverization, mixed again with a mixer, and then an appropriate amount of water is added, and the water dispersible granules are obtained after extrusion granulation with a granulator.

[0137] The preparation method of the emulsifiable concentrate is as follows: weigh the cinchona alkaloid derivative, emulsifier, solvent and filler according to the proportion, add them into a beaker, mix and stir evenly to obtain the emulsifiable concentrate.

[0138] Preparation Example 1, 20% Compound K10 Suspension

[0139] Compound K10 20%, nonylphenol polyoxyethylene ether 3%, alkyl naphthalene sulfonate 4%, calcium dodecylbenzene sulfonate 1.5%, ethylene glycol 2%, xanthan gum 1.2%, benzoic acid 1%, organosilicon 0.3%, water to 100%.

[0140] Formulation Example 2: 60% Compound K10 Water Dispersible Granules

[0141] Compound K10 60%, sodium naphthalene sulfonate 3.4%, alkylphenol polyoxyethylene ether formaldehyde condensate 3.6%, sodium lignin sulfonate 1.4%, modified starch 5%, sodium sulfate 4.2%, and bentonite to make up 100%.

[0142] Preparation Example 3, 20% Compound K11 Suspension

[0143] Compound K11 20%, high molecular carboxylate 4.2%, EO-PO block polymer 1.8%, alkyl naphthalene sulfonate 2.6%, glycerol 2%, magnesium aluminum silicate 1.3%, kason 1%, organic silicon 0.5%, water to make up to 100%.

[0144] Formulation Example 4, 40% Compound K9 Wettable Powder

[0145] Compound K9 40%, naphthalenesulfonic acid formaldehyde condensate sodium salt 5%, sodium lignin sulfonate 2%, white carbon black 1%, kaolin to make up 100%.

[0146] Preparation Example 5, 10% Compound K5 dry suspension

[0147] Compound K5 10%, sodium dodecylbenzenesulfonate 2%, naphthalenesulfonic acid formaldehyde condensate sodium salt 3.8%, corn starch to 100%.

[0148] Preparation Example 6, 30% Compound K6 Oil Suspension

[0149] Compound K6 30%, alkylbenzene polyoxyethylene ether phosphate 2%, sodium polycarboxylate 3%, calcium dodecylbenzene sulfonate 2%, silicone 1.8%, hydroxyethyl cellulose 2.6g, sodium benzoate 2%, N,N-dimethylformamide to 100%.

[0150] Formulation Example 7: 50% Compound K2 Water Dispersible Granules

[0151] Compound K2 50%, BX powder 3%, sodium dodecylbenzene sulfonate 2%, alkylphenol polyoxyethylene ether formaldehyde condensate 3.6%, modified starch 5%, ammonium sulfate 4%, diatomaceous earth 6%, and bentonite to make up 100%.

[0152] Formulation Example 8, 20% Compound K3 emulsifiable concentrate

[0153] Compound K3 20%, alkylphenol polyoxyethylene ether 5%, calcium dodecylbenzene sulfonate 3.5%, cyclohexanone 10%, and xylene to make up 100%.

[0154] V. Efficacy test for preventing and controlling rice bacterial blight:

[0155] Test agents: 50% water dispersible granules of compound K2 of Formulation Example 7, 20% emulsifiable concentrate of compound K3 of Formulation Example 8, 10% dry suspension of compound K5 of Formulation Example 5, 30% oil suspension of compound K6 of Formulation Example 6, 40% wettable powder of compound K9 of Formulation Example 4, 20% suspension of compound K10 of Formulation Example 1, and 20% suspension of compound K11 of Formulation Example 3.

[0156] Control agent: 20% thiophanate-methyl suspension, registration certificate PD20086024, Zhejiang Longwan Chemical Co., Ltd., commercially available.

[0157] Experimental design: A total of 8 agents were set up in the experiment. The leaves were dipped in the fungus and inoculated, and then sprayed with water (CK1). There were 9 treatments in total, 3 replicates per treatment, and a total of 27 plots, each with an area of ​​2.16m 2 , 72 seedlings were planted. Each plot was arranged in a random block, with a spacing of more than 40 cm between plots and a protective row around them. No other fungicide was sprayed during the experiment.

[0158] The inoculum concentration was 3×10 8 cfu / mL, 72 seedlings were inoculated in each plot, the inoculation date was October 7, 2023, the first spraying time was October 8 (24h after artificial inoculation) afternoon, and the second spraying time was October 15 afternoon. During the first spraying, there were sporadic diseased plants with rice white leaf disease. The water consumption for each spraying was 50kg / 667m 2 , use 3WBD-20L backpack manual sprayer to apply the pesticide.

[0159] No other fungicides were applied during the experiment. Sampling was carried out on October 22, 2023. Sampling was carried out at five points in each plot, and six seedlings were randomly surveyed at each point, for a total of 30 seedlings. The disease status of the two upper functional leaves of each seedling was graded.

[0160] The grading standards are as follows:

[0161] Grade 0: No disease;

[0162] Level 1: The leaf lesion area accounts for less than 10% of the leaf area;

[0163] Level 3: The leaf lesions account for 11-25% of the leaf area;

[0164] Level 5: The leaf lesions account for 26-45% of the leaf area;

[0165] Level 7: The leaf lesions account for 46-65% of the leaf area;

[0166] Level 9: The leaf spot area accounts for more than 65% of the leaf area.

[0167] Disease index (%) = [∑ (number of diseased leaves at each level × representative value at each level) / (total number of leaves surveyed × highest representative value)] × 100.

[0168] Relative protective effect (%) = (control disease index - treatment disease index) / control disease index × 100.

[0169] The results are shown in Table 3.

[0170] Table 3. Results of field efficacy test on control of rice bacterial blight

[0171] Test drug Dosage of preparation (g / mu) Disease index Relative efficacy (%) Compared with the control, the degree of enhancement 50% Compound K2 Water Dispersible Granules 50 0.37 92.00 29.33 20% Compound K3 EC 120 1.42 69.33 6.67 10% Compound K5 dry suspension 250 1.11 76.00 13.33 30% Compound K6 Oil Suspension 120 1.05 77.33 14.67 40% Compound K9 wettable powder 90 0.99 78.67 16.00 20% Compound K10 Suspension 120 0.56 88.00 25.33 20% Compound K11 Suspension 120 0.49 89.33 26.67 20% Thiophanate-copper suspension 180 1.73 62.67 Blank control / 4.63 / /

[0172] As shown in Table 3 above, the preparations containing cinchona alkaloid derivatives of the present invention, such as 20% compound K3 emulsifiable concentrate, have a 6%-29.33% higher control effect on rice bacterial blight than the control agent 20% thiophanate-copper suspension, and the control effect of compounds K2, K10, and K11 can be increased by more than 25%. In summary, cinchona alkaloid derivatives are superior to conventional agents 20% thiophanate-copper suspension in both indoor antibacterial effect and field efficacy test, and the compound has the value of further development and is expected to become a new agricultural antibacterial agent.

[0173] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit it. Although the present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that they can still modify the technical solutions described in the aforementioned embodiments, or make equivalent replacements for some of the technical features therein. However, these modifications or replacements do not deviate the essence of the corresponding technical solutions from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. A cinchona alkaloid derivative for preventing and controlling agricultural diseases, comprising a compound having a structural formula as shown in Formula I, or a pharmaceutically acceptable salt, a solvate and a tautomer thereof; in, In formula I, R1 is any of the following groups: R2 is one of substituted phenyl and C3-C10 alkyl; substituted phenyl includes halogenated phenyl, halogenated alkyl substituted phenyl, oxyalkyl substituted phenyl, cyanophenyl or C1-C5 alkyl substituted phenyl.

2. The cinchona alkaloid derivative according to claim 1, characterized in that R1 is Optionally, R2 includes halogenated phenyl, trifluoromethyl substituted phenyl or tert-butyl substituted phenyl; optionally R2 includes iodinated phenyl, fluorophenyl, chlorophenyl, trifluoromethyl substituted phenyl or tert-butyl substituted phenyl; R2 includes p-iodophenyl, p-fluorophenyl, p-chlorophenyl, p-trifluoromethylphenyl or p-tert-butylphenyl.

3. The cinchona alkaloid derivative according to claim 1, characterized in that It includes at least one of the compounds having the structural formulae K1 to K4, K6 to K15, or a pharmaceutically acceptable salt, solvate or tautomer thereof: Optionally, at least one of the compounds represented by any one of the structural formulae K2 to K4, K6, K7, K9 to K11, or a pharmaceutically acceptable salt, solvate or tautomer thereof is selected.

4. The cinchona alkaloid derivative according to any one of claims 1 to 3, characterized in that It is selected from at least one of the compounds having structural formulae K2, K6, K9 to K11, or a pharmaceutically acceptable salt, solvate or tautomer thereof; Optionally, it is selected from at least one of the compounds having structural formulae K2, K10, and K11, or a pharmaceutically acceptable salt, solvate, and tautomer thereof:

5. A method for preparing the cinchona alkaloid derivative according to any one of claims 1 to 4, characterized in that: include: The quinine alkaloids and amines are dissolved in an organic solvent, an acyl chloride compound is added, the mixture is stirred for reaction, and the mixture is purified to obtain a cinchona alkaloid derivative; The quinine alkaloid is selected from one or more of quinine sulfate, hydroquinine, quinidine, cinchonine and hydroquinidine; The acyl chloride compound is selected from one or more of 4-chlorobenzoyl chloride, 4-trifluoromethylbenzoyl chloride, p-methoxybenzoyl chloride, p-cyanobenzoyl chloride, p-fluorobenzoyl chloride, p-iodobenzoyl chloride, p-tert-butylbenzoyl chloride, n-butyryl chloride, n-valeryl chloride, hexanoyl chloride and isobutyryl chloride; Optionally, the amine is triethylamine; Optionally, the organic solvent is a chlorinated alkane, optionally dichloromethane.

6. A pesticide preparation, characterized in that: The active ingredient comprises the cinchona alkaloid derivative according to any one of claims 1 to 4 or the cinchona alkaloid derivative prepared by the preparation method according to claim 5; Optionally, it also includes an agriculturally acceptable carrier; Optionally, the weight percentage of the cinchona alkaloid derivative in the medicament is 1 to 99%; Optionally, the pesticide preparation is in the form of a suspension concentrate, a dry suspension concentrate, an oil suspension concentrate, a wettable powder or a water dispersible granule; Optionally, the pesticide formulation is used to prevent and control rice bacterial blight and / or citrus canker.

7. The use of cinchona alkaloid derivatives in preventing and controlling agricultural diseases, characterized in that: Cinchona alkaloid derivatives include compounds having a structural formula as shown in Formula I, or pharmaceutically acceptable salts, solvates and tautomers thereof; Wherein, in Formula I, R1 is any of the following groups: R2 is one of substituted phenyl and C3-C10 alkyl; substituted phenyl includes halogenated phenyl, halogenated alkyl substituted phenyl, oxyalkyl substituted phenyl, cyanophenyl or C1-C5 alkyl substituted phenyl.

8. The use according to claim 7, characterized in that: R1 is Optionally, R2 includes halogenated phenyl, trifluoromethyl substituted phenyl or tert-butyl substituted phenyl; optionally R2 includes iodinated phenyl, fluorophenyl, chlorophenyl, trifluoromethyl substituted phenyl or tert-butyl substituted phenyl; R2 includes p-iodophenyl, p-fluorophenyl, p-chlorophenyl, p-trifluoromethylphenyl or p-tert-butylphenyl.

9. The use according to claim 7 or 8, characterized in that: It includes at least one of the compounds having the structural formula shown in any one of Formulas K1 to K15, or a pharmaceutically acceptable salt, a solvate, and a tautomer thereof: Optionally, at least one compound selected from any one of the compounds having structural formulae K2 to K6, K7, K9 to K11, or a pharmaceutically acceptable salt, solvate or tautomer thereof; Optionally, it is selected from at least one of the compounds having structural formulae K2, K5, K6, K9 to K11, or a pharmaceutically acceptable salt, solvate or tautomer thereof; Optionally, it is selected from at least one of the compounds having structural formulae K2, K10, and K11, or a pharmaceutically acceptable salt, solvate, and tautomer thereof:

10. The use according to any one of claims 7 to 9, characterized in that: The plant bacterial diseases are one or more of rice bacterial blight and citrus canker.

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