Synthesis of amino acid derivatives containing 1, 3, 4-oxadiazole thioether and application of amino acid derivatives in resisting plant bacterial diseases

Abstract

The invention discloses an amino acid derivative containing 1, 3, 4-oxadiazole thioether, which is characterized in that the structural formula of the amino acid derivative is as follows: # imgabs0 #, M is phenyl or 4-phenol ethyl, and R is methyl, 2-naphthyl, benzyl or substituted benzyl. According to the invention, a series of novel amino acid derivatives containing 1, 3, 4-oxadiazole thioether are designed and synthesized, and a biological activity test shows that the compounds have excellent bacteriostatic activity on Xanthomonas oryzae pv. Oryzae and Citrus bacterial canker; in addition, the composition has good protection and prevention effects on citrus bacterial canker on citrus leaves.

Description

Technical Field

[0001] The present invention relates to the field of medicinal chemistry, and particularly to a preparation method of amino acid derivatives containing 1,3,4-oxadiazole thioether and their application in anti-plant pathogenic bacteria drugs. Background Art

[0002] Agriculture is the foundation of the national economy. Only by stabilizing agricultural production can food production and harvest be increased, and national peace and security be ensured. However, in the agricultural prevention and control system, crops are vulnerable to diseases caused by various plant pathogens (bacteria, fungi, and viruses), which restricts crop production and directly threatens global food security. Pesticides, as chemical products for controlling agricultural pests and regulating plant growth, play a key role in improving the comprehensive agricultural production capacity, protecting agricultural production, and promoting stable food production. Since the 1960s, when amino acid derivatives were reported as pesticides, amino acid pesticides have become one of the important directions for the creation of green pesticides. For example, Bayer launched the valinamide carbamate fungicide iprovalicarb in 1998, and its main target is oomycete pathogens. Currently, the structures of more than a dozen fungicidal drugs are designed based on the amino acid skeleton. However, in recent years, due to the long-term and repeated use of pesticides, the problem of pesticide resistance has become increasingly serious, and there is an urgent need to research and develop new green pesticides with novel structures, high efficiency, low toxicity, good selectivity, and high safety factors.

[0003] Our research group synthesized a class of phenylalanine derivatives containing "1,3,4-oxadiazole thioether" in CN113979964A, and its structural formula is as follows: In this structure, R is an alkyl group, a phenyl group, or a substituted phenyl group.

[0004] On the basis of previous research, replace the phenylalanine part in the structure with "β-phenylalanine" and "tyrosine" structures, hoping to discover a class of amino acid derivatives containing 1,3,4-oxadiazole thioether with novel structures and anti-plant pathogenic bacteria activities. Summary of the Invention

[0005] The technical problem to be solved by the present invention is to provide a class of amino acid derivatives containing 1,3,4-oxadiazole thioether for the prevention and control of plant bacterial diseases and their application in the prevention and control of bacterial diseases on citrus leaves.

[0006] The technical solution of the present invention: A class of amino acid derivatives containing 1,3,4-oxadiazole thioether, and its structural formula is as follows: Wherein M is a phenyl group or 4-phenol ethyl, and R is a methyl group, a 2-naphthyl group, a benzyl group, or a substituted benzyl group.

[0007] Preferably, the substitution position of the R-substituted benzyl is ortho, meta or para-disubstitution, and the substituents of the benzyl of R are fluorine, chlorine and bromine.

[0008] The substitution position of the R-substituted benzyl is mono-substitution or di-substitution at the ortho, meta or para-position.

[0009] A preparation method of an amino acid derivative containing 1,3,4-oxadiazole thioether, and the reaction formula is as follows:

[0010]

[0011] The application of the amino acid derivative containing 1,3,4-oxadiazole thioether in the preparation of an agent for preventing and controlling plant bacterial diseases; the plant bacterial diseases are Xanthomonas oryzae pv. oryzae and Xanthomonas axonopodis pv. citri.

[0012] The application of the amino acid derivative containing 1,3,4-oxadiazole thioether in the prevention and control of bacterial diseases on citrus leaves.

[0013] The beneficial effects of the present invention: On the basis of the structure of phenylalanine derivatives containing "1,3,4-oxadiazole thioether", the present invention replaces "phenylalanine" with "β-phenylalanine" and "tyrosine", and synthesizes a series of β-phenylalanine / tyrosine derivatives containing 1,3,4-oxadiazole thioether structure. Through the anti-plant pathogenic bacteria activity test of the compounds, it is found that this kind of compounds show good antibacterial activity against Xanthomonas oryzae pv. oryzae and Xanthomonas axonopodis pv. citri. In addition, it has good protective and control effects on citrus bacterial canker on citrus leaves. This kind of compounds has novel structures, and shows good in vitro and in vivo activities against plant pathogenic bacteria, providing an important scientific basis for the research and development of new pesticides.

[0014] It can be seen from Table 1 and Table 3 that under the concentration condition of 50 μg / mL, most of the target compounds show significant antibacterial activity against Xoo and Xac, and the activity reaches more than 90%.

[0015] As Figure 1 and Table 5 show, when compared with the leaves treated only with water (blank control), the CK treatment (negative control) causes obvious damage to citrus leaves; under the concentration condition of 200 μg / mL, the target compound I 11 shows good protective and therapeutic activities against citrus canker, which are 90.67% and 73.10% respectively, both better than the commercial control agent bismerthiazol 61.59% and 40.84%. Systematic analysis finds that compound I 11 shows strong comprehensive activities in in vitro and in vivo tests, and this kind of active compounds show potential application value in inhibiting plant pathogenic bacteria. Description of the Drawings

[0016] Figure 1 The compound and the commercial agent bismerthiazol have good protective and control effects on citrus bacterial canker on citrus leaves. Specific embodiments

[0017] Synthetic route of amino acid derivatives containing 1,3,4-oxadiazole thioether:

[0018]

[0019] Using β-phenylalanine and tyrosine as starting materials respectively, the target compounds I and II are synthesized through esterification, Boc group protection, hydrazinolysis, substitution, ring closure and de-Boc group.

[0020] Preparation of intermediates Preparation of intermediate ester (B)

[0021]

[0022] β-Phenylalanine (5.0 mmol) or tyrosine (5.5 mmol), methanol (8.0 mL) (MeOH) and 98% sulfuric acid (2.5 mmol) were successively added to a 50 mL round-bottom flask, heated under reflux at 100 °C, and the reaction progress was monitored by TLC. After the reaction was completed, the solvent was removed by vacuum distillation, and then 10% sodium hydroxide solution was added to adjust the pH to 7-8. Then it was extracted with dichloromethane (DCM) and purified by column chromatography (DCM / MeOH = 100 / 1, v / v) to obtain intermediate B. The physical and chemical data and spectroscopic data are as follows:

[0023]

[0024] Methyl 3-amino-3-phenylpropionate (B1): Pale yellow oily liquid, yield 72%. 1 H NMR (500 MHz, DMSO-d6) δ: 7.38 (d, J = 10.0 Hz, 2H, benzene H), 7.30 (t, J = 15.0 Hz, 2H, benzene H), 7.21 (t, J = 10.0 Hz, 1H, benzene H), 4.20 (t, J = 15.0 Hz, 1H, CH NH2), 3.55 (s, 3H, CH3), 2.62–2.56 (m, 2H, CH CH2 ); 13 C NMR (126 MHz, DMSO-d6) δ: 172.26, 146.50, 128.68, 127.24, 126.77, 53.18, 51.73, 44.60.

[0025]

[0026] Methyl tyrosine (B2): White solid, yield 77%, melting point 182–183 °C. 1 H NMR (400 MHz, DMSO-d6) δ: 6.93–6.95 (m, 2H, benzene H), 6.64–6.66 (m, 2H, benzene H), 3.56 (s, 3H, CH3), 3.47 (t, J = 12 Hz, 1H, CH CH2), 2.63–2.76 (m, 2H, CH CH2 ); 13 C NMR (101 MHz, DMSO-d6) δ: 175.98, 156.30, 130.54, 128.22, 115.41, 56.41, 51.74. Preparation of Boc-protected amino acid ester intermediate (C)

[0027]

[0028] Intermediate ester B (5.6 mmol), triethylamine (16.7 mmol), methanol (8.0 mL), and Boc anhydride (6.7 mmol) were successively added to a 50 mL round-bottom flask, and the mixture was heated under reflux at 100 °C. The reaction progress was monitored by TLC. After the reaction was completed, the solvent was removed by vacuum distillation, and the pH value was adjusted to 4–5 with 5% hydrochloric acid. The mixture was extracted with ethyl acetate (EA), and the crude product was separated and purified by column chromatography (DCM / MeOH = 100 / 1, v / v) to obtain intermediate C. The physical and chemical data and spectroscopic data are as follows:

[0029]

[0030] Methyl 3-((tert-butoxycarbonyl)amino)-3-phenylpropionate (C1): White solid, yield 92%, melting point 80–81 °C. 1 H NMR (500 MHz, DMSO-d6) δ: 7.33–7.30 (m, 4H, benzene H), 7.27–7.21 (m, 1H, benzeneH), 4.94–4.89 (m, 1H, CH CH2), 3.54 (s, 3H, CH3), 2.77–2.65 (m, 2H, CH CH2 ), 1.35 (d, J = 60.0 Hz, 9H, (CH3)3); 1313C NMR (126 MHz, DMSO-d6) δ: 71.21, 155.24, 143.29, 128.82, 127.53, 126.80, 78.42, 51.89, 51.58, 41.53, 28.70.

[0031]

[0032] (tert-Butoxycarbonyl)tyrosine methyl ester (C2): White solid, yield 85%, melting point 83–84 °C. 1 1H NMR (400 MHz, CDCl3) δ: 7.95–7.93 (d, J = 8.0 Hz, 2H, benzene H), 6.74–6.72 (d, J = 8.0 Hz, 2H, benzene H), 4.55–4.50 (m, 1H, CH CH2), 3.70 (s, 3H, CH3), 3.04–2.90 (m, 2H, CH CH2 ), 1.41 (s, 9H, (CH3)3); 13 13C NMR (101 MHz, CDCl3) δ: 172.77, 155.33, 130.34, 127.25, 115.56, 80.34, 54.66, 52.36, 37.54, 28.32.

[0033] Preparation of Intermediate Hydrazide (D)

[0034]

[0035] Intermediate C (3.6 mmol), methanol (8.0 mL) and 80% hydrazine hydrate (35.8 mmol) were added to a 50 mL round-bottom flask, heated to reflux at 100 °C, and the reaction progress was monitored by TLC. After the reaction was completed, the solvent was removed by distillation under reduced pressure, and the residue was extracted with dichloromethane and purified by column chromatography (DCM / MeOH = 200 / 1, v / v) to obtain Intermediate D. The physical and chemical data and spectroscopic data are as follows:

[0036]

[0037] (3-Hydrazino-3-oxo-1-phenylpropyl)carbamic acid tert-butyl ester (D1): White solid, yield 85%, melting point 119–120 °C. 1 1H NMR (500 MHz, DMSO-d6) δ: 8.96 (s, 1H, CO NH ), 7.45 (d, J = 10.0 Hz, 1H, CH NH ), 7.30–7.25 (m, 5H, benzene H), 4.92–4.87 (m, 1H,CH NH), 4.14 (s, 2H, NH2), 2.46–2.38 (m, 2H, CH2), 1.34 (s, 9H, O(CH3)3); 13 C NMR (126 MHz, DMSO-d6) δ: 169.27, 155.20, 143.99, 128.67, 127.25, 126.78, 78.32, 51.84, 41.22, 28.75.

[0038]

[0039] (1-Hydrazino-3-(4-hydroxyphenyl)-1-oxopropan-2-yl) tert-butyl carbamate (D2): White solid, yield 87%, melting point 134–135 °C. 1 H NMR (500 MHz, DMSO-d6) δ: 9.19 (s, 1H, CO NH ), 9.09 (s, 1H, OH), 7.02 (d, J = 5.0 Hz, 2H, benzene H), 6.89 (d, J = 10.0 Hz, 1H, CH NH ), 6.64 (d, J = 10.0 Hz, 2H, benzene H), 4.21 (s, 2H, NH2), 4.01–3.97 (m, 1H, CH NH), 2.75–2.58 (m, 2H, CH2), 1.30 (s, 9H, O(CH3)3); 13 C NMR (126 MHz, DMSO-d6) δ: 171.74, 156.21, 155.64, 130.60, 128.69, 115.31, 78.34, 55.33, 37.54, 28.70.

[0040] Preparation of Intermediate 2-Substituted-1,3,4-Oxadiazole-5-Thiol (E)

[0041]

[0042] Add intermediate D (17.9 mmol) to a 100 mL round-bottom flask, then add 30 mL of anhydrous ethanol containing potassium hydroxide (KOH) (35.8 mmol). After 15 min, add CS2 (53.7 mmol), and stir and mix overnight at room temperature. Then add KOH (35.8 mmol) again, stir and reflux. After the reaction is completed, remove the solvent by distillation under reduced pressure, and adjust the pH to 4–5 with 5% hydrochloric acid. At this time, intermediate E precipitates, and the physical and chemical data and spectroscopic data are as follows:

[0043]

[0044] (2-(5-Mercapto-1,3,4-oxadiazol-2-yl)-1-phenylethyl) tert-butyl carbamate (E1): Pale yellow solid, yield 87%, melting point 179–180 °C. 1 H NMR (500 MHz, DMSO-d6) δ: 7.59 (d, J = 10.0 Hz, 1H, CH NH ), 7.31–7.29 (m, 4H, benzene H), 7.24–7.21 (m, 1H, benzene H), 4.88–4.85 (m, 1H, CH NH), 3.03–2.92 (m, 2H, CH2), 1.33 (s, 9H, O(CH3)3); 13 C NMR (126 MHz, DMSO-d6) δ: 178.95, 161.20, 155.31, 143.10, 128.84, 127.62, 126.83, 78.54, 55.46, 52.62, 49.12, 33.23, 28.70.

[0045]

[0046] (2-(4-Hydroxyphenyl)-1-(5-mercapto-1,3,4-oxadiazol-2-yl)ethyl) tert-butyl carbamate (E2): Yellow oil, yield 91%. 1 H NMR (400 MHz, DMSO-d6) δ: 14.46 (s, 1H, SH), 9.27 (s, 1H, OH), 7.02–6.99 (d, J = 12.0, 2H, benzene H), 6.66–6.64 (d, J = 8.0, 2H, benzene H), 4.75–4.69 (m, 1H, CH CH2), 3.01–2.87 (m, 2H, CH CH2 ), 1.32 (s, 9H, (CH3)3); 13 C NMR (101 MHz, DMSO-d6) δ: 178.18, 164.12, 156.53, 155.39, 130.61, 127.03, 115.50, 79.18, 55.39, 49.12, 28.53.

[0047] Preparation of intermediate 2-substituted-1,3,4-oxadiazole-5-thioether (F)

[0048]

[0049] Take 3.0 mmol of intermediate E in a 50 mL round-bottom flask, add acetonitrile (5.0 mL), water (5.0 mL), potassium carbonate (4.5 mmol) and methyl iodide / substituted benzyl (4.5 mmol) thereto, stir at room temperature, and monitor the reaction progress by TLC. After the reaction is completed, remove the solvent by distillation under reduced pressure, then extract with ethyl acetate, and purify by column chromatography (PE / EA = 30 / 1, v / v) to obtain intermediate F.

[0050] Target compound I n and II n Synthesis

[0051] (1) Take the synthesis of target compound I1 as an example

[0052]

[0053] Add 8.0 mL of dichloromethane and 2.0 mL of trifluoroacetic acid to the round-bottom flask containing intermediate F, then stir at room temperature overnight, and monitor the reaction progress by TLC. After the reaction is completed, quench with saturated sodium bicarbonate solution, adjust the pH to 8 - 9, then extract with dichloromethane, and perform gradient elution using a mixed system of dichloromethane and methanol to obtain target compound I1. Yellow oil, yield 51%. 1 H NMR (500 MHz, DMSO-d6) δ: 7.51 (s, 1H, benzene H), 7.37–7.34 (m, 4H, benzene H), 7.33 (s, 1H, benzene H), 7.30–7.27 (m, 2H, benzene H), 7.22–7.19 (m, 1H, benzene H), 4.43 (s, 2H, SCH2), 4.22 (t, J = 15 Hz, 1H, CH CH2), 3.14 - 3.04 (m, 2H, CH CH2 ); 13 C NMR (126 MHz, DMSO-d6) δ: 167.00, 162.83, 145.89, 139.94, 133.49, 130.93, 129.33, 128.73, 128.24, 128.19, 127.46, 126.74, 54.30, 35.71, 35.44; HRMS: calcd for C 17 H 16 ClN3OS, [M + H] + 346.07754, found 346.0767.

[0054] The synthesis methods of other target compounds are similar to that of target compound I1.

[0055] (2) Structures and physicochemical data of the target compounds

[0056]

[0057] I2, yellow oil, yield 55%. 1 H NMR (500 MHz, DMSO-d6) δ: 7.44–7.42 (m, 2H, benzene H), 7.40–7.38 (m, 2H, benzene H), 7.35–7.33 (m, 2H, benzene H), 7.30–7.27 (m, 2H, benzene H), 7.23–7.20 (m, 1H, benzene H), 4.42 (s, 2H, SCH2), 4.21 (t, J = 15 Hz, 1H, CH CH2), 3.14–3.05 (m, 2H, CH CH2 ); 13 C NMR (126 MHz, DMSO-d6) δ: 166.99, 162.83, 145.90, 136.43, 132.84, 131.41, 129.04, 128.73, 127.46, 126.76, 54.31, 35.66, 35.42; HRMS: calcd for C 17 H 17 ClN3OS, [M + H] + 346.07754, found 346.0767.

[0058]

[0059] I3: pale yellow solid, yield 45%, melting point 106–107 °C. 1 H NMR (500 MHz, DMSO-d6) δ: 7.66 (d, J = 5 Hz, 1H, benzene H), 7.53 (m, J = 10 Hz, 1H, benzene H), 7.38–7.35 (m, 3H, benzene H), 7.31–7.28 (m, 2H, benzene H), 7.26–7.24 (m, 1H, benzene H), 7.23–7.20 (m, 1H, benzene H), 4.51 (s, 2H, SCH2), 4.24 (t, J = 15 Hz, 1H, CH CH2), 3.15–3.08 (m, 2H, CHCH2); 1313C NMR(126MHz,DMSO-d6)δ:167.17,162.52,145.91,135.93,133.42,132.07,130.67,128.74,128.57,127.48,126.77,124.53,54.31,37.27,35.72; HRMS(ESI):calcd for C 17 H 16 BrN3OS,[M+Na] + 412.00896,found:412.0084.

[0060]

[0061] I4: Pale yellow solid, yield 41%, melting point 105 - 106 °C. 1 1H NMR(500MHz,DMSO-d6)δ:7.55–7.50(m,2H,benzene H),7.36–7.34(m,4H,benzene H),7.30–7.27(m,2H,benzene H),7.23–7.21(m,1H,benzene H),4.39(s,2H,SCH2),4.26(t,J = 15Hz,1H, CH CH2),3.10–3.20(m,2H,CH CH2 ); 13 13C NMR(101MHz,DMSO-d6)δ:166.94,162.75,145.88,136.81,131.89,131.67,128.66,127.39,126.70,121.35,54.26,35.62,35.42; HRMS:calcd for C 17 H 17 ON3BrS,[M+H] + 390.02702,found 390.0263.

[0062]

[0063] I5: Pale yellow oil, yield 56%. 11H NMR (400 MHz, DMSO-d6) δ: 7.47–7.45 (m, 3H, benzene H), 7.35–7.33 (m, 2H, benzene H), 7.29–7.25 (m, 3H, benzene H), 7.22–7.18 (m, 1H, benzene H), 4.48 (s, 2H, SCH2), 4.21 (t, J = 16 Hz, 1H, CH CH2), 3.13–3.04 (m, 2H, CH CH2 ); 13 13C NMR (101 MHz, DMSO-d6) δ: 166.94, 162.74, 148.70, 145.83, 140.22, 130.97, 128.64, 128.63, 127.39, 126.68, 121.92, 120.67, 54.25, 35.61, 35.31; 19 19F NMR (376 MHz, DMSO-d6) δ: -56.74; HRMS: calcd for C 18 H 17 O2N3F3S, [M+H] + 396.09881, found 396.0979.

[0064]

[0065] I6: Pale yellow oil, yield 30%. 1 1H NMR (500 MHz, DMSO-d6) δ: 7.55–7.53 (m, 2H, benzene H), 7.35–7.32 (m, 4H, benzene H), 7.30–7.27 (m, 2H, benzene H), 7.22–7.19 (m, 1H, benzene H), 4.47 (s, 2H, SCH2), 4.22 (t, J = 15 Hz, 1H, CH CH2), 3.14–3.05 (m, 2H, CH CH2 ); 13 13C NMR (126 MHz, DMSO-d6) δ: 167.00, 162.84, 148.22, 145.91, 136.94, 131.49, 128.71, 127.45, 126.75, 121.63, 54.31, 35.68, 35.26; 19 19F NMR (471 MHz, DMSO-d6) δ: -56.71; HRMS: calcd for C 18 H 17O2N3F3S, [M+H] + 396.09881, found 396.0979.

[0066]

[0067]

[0068] I7: Yellow oil, yield 63%. 1 H NMR (500 MHz, DMSO-d6) δ: 7.7 (d, J = 10 Hz, 1H, benzene H), 7.68–7.67 (m, 2H, benzene H), 7.57–7.54 (m, 1H, benzene H), 7.36–7.35 (m, 2H, benzene H), 7.30–7.27 (m, 2H, benzene H), 7.20–7.23 (m, 1H, benzene H), 4.59 (s, 2H, SCH2), 4.23 (t, J = 15 Hz, 1H, CH CH2), 3.16–3.07 (m, 2H, CH CH2 ); 13 C NMR (126 MHz, DMSO-d6) δ: 167.25, 162.42, 145.88, 134.79, 133.60, 132.50, 129.28, 128.73, 127.47, 126.94, 126.90, 126.76, 54.31, 35.71, 33.45; 19 F NMR (471 MHz, DMSO-d6) δ: -57.99; HRMS: calcd for C 18 H 17 O2N3F3S, [M+H] + 380.10389, found 380.1029.

[0069]

[0070] I8: Yellow oil, yield 44%. 1 H NMR (500 MHz, DMSO-d6) δ: 7.91–7.87 (m, 4H, benzene H), 7.56–7.50 (m, 3H, benzene H), 7.32–7.31 (m, 2H, benzene H), 7.26–7.23 (m, 2H, benzene H), 7.20–7.17 (m, 1H, benzene H), 4.60 (s, 2H, SCH2), 4.20 (t, J = 10 Hz, 1H,CH CH2), 3.14–3.04 (m, 2H, CH CH2 ); 13 C NMR (126 MHz, DMSO-d6) δ: 166.96, 162.94, 145.91, 134.65, 133.22, 132.82, 128.82, 128.70, 128.22, 128.17, 128.11, 127.46, 127.43, 126.98, 126.80, 126.74, 54.31, 36.63, 35.72;HRMS: calcd for C 21 H 20 ON3S, [M+H] + 362.13216, found 360.1313.

[0071]

[0072] I9: Yellow oil, yield 39%. 1 H NMR (500 MHz, DMSO-d6) δ: 7.58 (d, J = 10 Hz, 1H, benzene H), 7.45–7.38 (m, 2H, benzene H), 7.36–7.34 (m, 2H, benzene H), 7.30–7.27 (m, 2H, benzene H), 7.23–7.20 (m, 1H, benzene H), 4.43 (s, 2H, SCH2), 4.22 (t, J = 15 Hz, 1H, CH CH2), 3.14–3.05 (m, 2H, CH CH2 ); 13 C NMR (126 MHz, DMSO-d6) δ: 167.23, 162.35, 145.93, 133.40, 128.72, 128.23, 127.45, 126.76, 123.87, 122.08, 119.55, 119.35, 54.31, 35.72, 29.71; 19 F NMR (471 MHz, DMSO-d6) δ: -113.48;HRMS: calcd for C 17 H 16 ON3BrFS, [M+H] + 480.01760, found 480.0168.

[0073]

[0074] I 10: Yellow oil, yield 62%. 1 H NMR (500 MHz, DMSO-d6) δ: 7.67 (s, 1H, benzene H), 7.57–7.55 (m, 1H, benzene H), 7.31–7.23 (m, 5H, benzene H), 7.18–7.16 (m, 1H, benzeneH), 4.39 (s, 2H, SCH2), 4.18 (t, J = 10 Hz, 1H, CHCH2), 3.09–3.02 (m, 2H, CHCH2); 13 C NMR (126 MHz, DMSO-d6) δ: 167.01, 162.72, 145.74, 138.83, 131.51, 131.42, 131.19, 130.81, 129.92, 128.73, 127.50, 126.76, 54.27, 35.59, 34.81; HRMS: calcd for C 17 H 16 ON3FC l2 S, [M + H] + 380.03856, found 380.0376.

[0075]

[0076] I 11 : Yellow solid, yield 41%, melting point 100 - 101 °C. 1 H NMR (500 MHz, DMSO-d6) δ: 7.68 (s, 1H, benzene H), 7.55 (d, J = 5 Hz, 1H, benzene H), 7.42–7.40 (m, 1H, benzene H), 7.36 (d, J = 10 Hz, 2H, benzene H), 7.29 (t, J = 15 Hz, 2H, benzene H), 7.22 (t, J = 15 Hz, 1H, benzene H), 4.49 (s, 2H, SCH2), 4.23 (t, J = 10 Hz, 1H, CH CH2), 3.16–3.06 (m, 2H, CH CH2 ); 13 C NMR (126 MHz, DMSO-d6) δ: 167.23, 162.34, 145.81, 134.79, 134.05, 133.69, 133.29, 129.62, 128.74, 128.12, 127.49, 126.79, 54.28, 35.62, 34.02; HRMS: calcd for C 17 H16 ON3Cl2S, [M+H] + 380.03856, found 380.0379.

[0077]

[0078] I 12 : Yellow oil, yield 40%. 1 H NMR (500 MHz, DMSO-d6) δ: 7.55–7.50 (m, 1H, benzene H), 7.37–7.35 (m, 2H, benzene H), 7.30–7.26 (m, 3H, benzene H), 7.23–7.20 (m, 1H, benzene H), 7.08–7.04 (m, 1H, benzene H), 4.44 (s, 2H, SCH2), 4.22 (t, J=10 Hz, 1H, CH CH2), 3.14–3.05 (m, 2H, CH CH2 ); 13 C NMR (126 MHz, DMSO-d6) δ: 167.19, 162.45, 145.94, 133.08, 128.73, 127.46, 126.76, 120.53, 112.24, 104.67, 54.31, 35.71, 29.66; 19 F NMR (471 MHz, DMSO-d6) δ: -109.82, -112.07; HRMS: calcd for C 17 H 16 ON3F2S, [M+H] + 348.09767, found 348.0971.

[0079]

[0080] I 13 : White solid, yield 39%, melting point 84 - 85 °C. 1 H NMR (500 MHz, DMSO-d6) δ: 7.38–7.34 (m, 3H, benzene H), 7.31–7.27 (m, 3H, benzene H), 7.24–7.19 (m, 2H, benzene H), 4.45 (s, 2H, SCH2), 4.22 (t, J=10 Hz, 1H, CH CH2), 3.15–3.05 (m, 2H, CH CH2 ); 1313C NMR (126 MHz, DMSO-d6) δ: 167.23, 162.40, 145.92, 128.72, 127.46, 126.74, 118.28, 118.09, 117.69, 117.50, 117.15, 116.96, 54.30, 35.75, 29.85; 19 19F NMR (471 MHz, DMSO-d6) δ: -118.31, -122.17; HRMS: calcd for C 17 H 16 ON3F2S, [M+H] + 348.09767, found 348.0969.

[0081]

[0082] I 14 : Yellow oil, yield 50%. 1 1H NMR (500 MHz, DMSO-d6) δ: 7.35–7.33 (m, 2H, benzene H), 7.29–7.26 (m, 2H, benzene H), 7.22–7.16 (m, 4H, benzene H), 4.45 (s, 2H, SCH2), 4.21 (t, J = 10 Hz, 1H, CH CH2), 3.14–3.05 (m, 2H, CH CH2 ); 13 13C NMR (126 MHz, DMSO-d6) δ: 167.09, 162.69, 145.93, 142.00, 128.71, 127.45, 126.72, 112.86, 112.66, 104.00, 103.79, 54.31, 35.72, 35.20; 19 19F NMR (471 MHz, DMSO-d6) δ: -109.60; HRMS: calcd for C 17 H 16 ON3F2S, [M+H] + 348.09767, found 348.0968.

[0083]

[0084] I 15 : Pale yellow oil, yield 45%. 11H NMR (500 MHz, DMSO-d6) δ: 7.53–7.49 (m, 1H, benzene H), 7.42–7.20 (m, 7H, benzene H), 4.43 (s, 2H, SCH2), 4.22 (t, J = 15 Hz, 1H, CH CH2), 3.14–3.05 (m, 2H, CH CH2 ); 13C NMR (126 MHz, DMSO-d6) δ: 167.03, 162.75, 145.94, 135.22, 128.70, 127.44, 126.73, 118.66, 118.52, 118.12, 117.99, 54.30, 35.67, 35.04; 19 19F NMR (471 MHz, DMSO-d6) δ: -138.26, -139.73; HRMS: calcd for C 17 H 16 ON3F2S, [M+H] + 348.09767, found 348.0970.

[0085]

[0086] II1: Yellow oil, yield 58%. 1 1H NMR (500 MHz, DMSO-d6) δ: 9.25 (s, 1H, OH), 6.93–6.91 (m, 2H, benzene H), 6.63–6.61 (m, 2H, benzene H), 4.18 (t, J = 15 Hz, 1H, CH CH2), 2.89–2.88 (m, 2H, CH CH2 ), 2.66 (s, 1H, CH3); 13 13C NMR (126 MHz, DMSO-d6) δ: 170.76, 164.35, 156.42, 130.57, 128.01, 115.53, 50.24, 41.03, 14.73; HRMS: calcd for C 11 H 14 O2N3S, [M+H] + 252.08012, found 252.0797.

[0087]

[0088] II2: White solid, yield 49%, melting point 118 - 119 °C. 11H NMR (500 MHz, DMSO-d6) δ: 9.24 (s, 1H, OH), 7.48–7.46 (m, 3H, benzene H), 7.30–7.28 (m, 1H, benzene H), 6.85–6.84 (m, 2H, benzene H), 6.60–6.59 (m, 2H, benzene H), 4.52 (s, 2H, SCH2), 4.15 (t, J = 15 Hz, 1H, CHCH2), 2.86 (d, J = 5 Hz, 2H, CHCH2); 13 13C NMR (126 MHz, DMSO-d6) δ: 171.03, 162.80, 156.40, 148.79, 140.30, 131.00, 130.51, 128.64, 127.95, 121.99, 120.72, 115.49, 50.30, 40.98, 35.32; 19 19F NMR (376 MHz, DMSO-d6) δ: -56.64; HRMS: calcd for C 18 H 17 O3N3F3S, [M + H] + 412.09372, found 412.0929.

[0089]

[0090] II3: Pale yellow solid, yield 62%, melting point 111 - 112 °C. 1 1H NMR (400 MHz, DMSO-d6) δ: 9.27 (s, 1H, OH), 7.57–7.54 (m, 2H, benzene H), 7.34–7.32 (d, J = 8 Hz, 2H, benzene H), 6.86–6.84 (m, 2H, benzene H), 6.61–6.59 (m, 2H, benzene H), 4.50 (s, 2H, SCH2), 4.16 (t, J = 16 Hz, 1H, CH CH2), 2.86 (d, J = 8 Hz, 2H, CH CH2 ); 13C NMR (101 MHz, DMSO-d6) δ: 170.95, 162.79, 156.33, 148.15, 136.92, 131.42, 130.46, 127.90, 121.58, 115.43, 50.22, 40.92, 35.14; 19 19F NMR (376 MHz, DMSO-d6) δ: -56.82; HRMS: calcd for C 18 H17 O3N3F3S, [M+H] + 412.09372, found 412.0928.

[0091]

[0092] II4: Yellow solid, yield 49%, melting point 101 - 102 °C. 1 H NMR (500 MHz, DMSO-d6) δ: 9.23 (s, 1H, OH), 7.48–7.45 (m, 2H, benzene H), 7.17–7.14 (m, 2H, benzene H), 6.87–6.85 (m, 2H, benzene H), 6.62–6.60 (m, 2H, benzene H), 4.46 (s, 2H, SCH2), 4.15 (t, J = 15 Hz, 1H, CH CH2), 2.87 (d, J = 5 Hz, 2H, CH CH2 ; 13 C NMR (101 MHz, DMSO-d6) δ: 170.89, 162.86, 156.34, 133.47, 131.59, 131.51, 130.48, 127.90, 115.93, 115.72, 115.44, 50.20, 40.92, 35.31; 19 F NMR (376 MHz, DMSO-d6) δ: -114.44; HRMS: calcd for C 17 H 17 O2N3FS, [M+H] + 346.10200, found 346.1012.

[0093]

[0094] II5: Pale yellow solid, yield 54%, melting point 134 - 135 °C. 1 H NMR (500 MHz, DMSO-d6) δ: 9.24 (s, 1H, OH), 7.54 (s, 1H, benzene H), 7.40–7.38 (m, 1H, benzene H), 7.36–7.35 (m, 2H, benzeneH), 6.85–6.83 (m, 2H, benzene H), 6.60–6.59 (m, 2H, benzene H), 4.47 (s, 2H, SCH2), 4.16 (t, J = 15 Hz, 1H, CH CH2), 2.86 (d, J = 10 Hz, 2H, CHCH2 ); 13 C NMR (126 MHz, DMSO-d6) δ: 170.97, 162.82, 156.39, 140.00, 133.50, 130.92, 130.52, 129.36, 128.23, 128.20, 127.94, 115.50, 50.30, 40.97, 35.35; HRMS: calcd for C 18 H 20 O2N3S, [M+H] + 342.112707, found 342.1266

[0095]

[0096] II6: White solid, yield 58%, melting point 106 - 107 °C. 1 H NMR (500 MHz, DMSO-d6) δ: 9.27 (s, 1H, OH), 7.45–7.43 (m, 2H, benzene H), 7.40–7.38 (m, 2H, benzene H), 6.85–6.84 (m, 2H, benzene H), 6.61–6.59 (m, 2H, benzene H), 4.45 (s, 2H, SCH2), 4.16 (t, J = 15 Hz, 1H, CH CH2), 2.86 (d, J = 10 Hz, 2H, CH CH2 ); 13 C NMR (126 MHz, DMSO-d6) δ: 170.97, 162.82, 156.39, 140.00, 133.50, 130.92, 130.52, 129.36, 128.23, 128.20, 127.94, 115.50, 50.30, 40.97, 35.35; HRMS: calcd for C 17 H 17 O2N3ClS, [M+H] + 362.07245, found 362.0714.

[0097]

[0098] II7: Pale yellow oil, yield 36%. 11H NMR (500 MHz, DMSO-d6) δ: 9.25 (s, 1H, OH), 7.67 (d, J = 10 Hz, 1H, benzene H), 7.55–7.53 (m, 1H, benzene H), 7.36 (t, J = 15 Hz, 1H, benzene H), 7.28–7.25 (m, 2H, benzene H), 6.89–6.87 (m, 2H, benzene H), 6.61–6.59 (m, 2H, benzene H), 4.45 (s, 2H, SCH2), 4.17 (t, J = 15 Hz, 1H, CH CH2), 2.89–2.87 (m, 2H, CH CH2 ); 13 13C NMR (126 MHz, DMSO-d6) δ: 171.20, 162.50, 156.40, 135.92, 133.46, 132.05, 130.70, 130.56, 128.57, 127.98, 124.53, 115.51, 50.28, 40.97, 37.20; HRMS: calcd for C 17 H 17 O2N3BrS, [M + H] + 406.02194, found 406.0209.

[0099]

[0100] II8: Pale yellow solid, yield 52%, melting point 103 - 104 °C. 1 1H NMR (500 MHz, DMSO-d6) δ: 9.30 (s, 1H, OH), 7.54–7.52 (m, 2H, benzene H), 7.38–7.37 (m, 2H, benzene H), 6.85–6.84 (m, 2H, benzene H), 6.61–6.59 (m, 2H, benzene H), 4.44 (s, 2H, SCH2), 4.16 (t, J = 15 Hz, CH CH2), 2.86 (d, J = 5 Hz, 2H, CH CH2 ); 13 13C NMR (126 MHz, DMSO-d6) δ: 171.02, 162.79, 156.41, 136.90, 131.96, 131.71, 130.53, 127.94, 121.42, 115.51, 50.27, 40.98, 35.44; HRMS: calcd for C 17 H 17O2N3BrS, [M+H] + 346.10200, found 346.1011.

[0101]

[0102] II9: Yellow oil, yield 48%. 1 H NMR(500MHz, DMSO-d6) δ: 9.29(s, 1H, OH), 7.33(d, J = 10Hz, 1H, benzene H), 7.22–7.21(m, 2H, benzene H), 7.15–7.12(m, 1H, benzene H), 6.89–6.88(m, 2H, benzene H), 6.62–6.60(m, 2H, benzene H), 4.44(s, 2H, SCH2), 4.17(t, J = 15Hz, 1H, CH CH2), 2.88(d, J = 5Hz, 2H, CH CH2 ), 2.36(s, 3H, CH3); 13 C NMR(126MHz, DMSO-d6) δ: 171.01, 162.86, 156.42, 137.29, 134.31, 131.01, 130.56, 130.47, 128.73, 127.97, 126.66, 115.52, 50.28, 41.02, 34.81, 19.27; HRMS: calcd for C 18 H 20 O2N3S, [M+H] + 342.12707, found 342.1263.

[0103]

[0104] II 10 : Pale yellow solid, yield 58%, melting point 122 - 123 °C. 1 H NMR(500MHz, DMSO-d6) δ: 9.25(s, 1H, OH), 7.24–7.21(m, 3H, benzene H), 7.10–7.09(m, 1H, benzene H), 6.86–6.83(m, 2H, benzene H), 6.61–6.58(m, 2H, benzene H), 4.42(s, 2H, SCH2), 4.16(t, J = 10Hz, 1H, CH CH2), 2.87(d, J = 5Hz, 2H, CH CH2), 2.27 (s, 3H, CH3); 13 C NMR (126 MHz, DMSO-d6) δ: 170.86, 163.03, 156.38, 138.28, 136.96, 130.54, 130.07, 129.01, 128.93, 127.96, 126.59, 115.50, 50.31, 41.00, 36.20, 21.45; HRMS: calcd for C 18 H 20 O2N3S, [M+H] + 342.12707, found 342.1264.

[0105]

[0106] II 11 : Yellow solid, yield 43%, melting point 107 - 108 °C. 1 H NMR (500 MHz, DMSO-d6) δ: 9.26 (s, 1H, OH), 7.30–7.28 (m, 2H, benzene H), 7.13 (d, J = 10 Hz, 2H, benzene H), 6.86–6.84 (m, 2H, benzene H), 6.61–6.59 (m, 2H, benzene H), 4.42 (s, 2H, SCH2), 4.16 (t, J = 15 Hz, 1H, CH CH2), 2.87 (d, J = 5 Hz, 2H, CH CH2 ), 2.26 (s, 3H, CH3); 13 C NMR (126 MHz, DMSO-d6) δ: 170.87, 163.03, 156.39, 137.57, 133.99, 130.55, 129.65, 129.43, 127.97, 115.50, 50.29, 40.99, 36.06, 21.25. HRMS: calcd for C 18 H 20 O2N3S, [M+H] + 342.12707, found 342.1262.

[0107]

[0108]

[0109] II 12 : Yellow solid, yield 39%, melting point 94 - 95 °C. 11H NMR (500 MHz, DMSO-d6) δ: 9.26 (s, 1H, OH), 7.77 (d, J = 10 Hz, 1H, benzene H), 7.69–7.65 (m, 2H, benzene H), 7.57–7.53 (m, 1H, benzene H), 6.89–6.86 (m, 2H, benzene H), 6.62–6.59 (m, 2H, benzene H), 4.63 (s, 2H, SCH2), 4.19 (t, J = 15 Hz, 1H, CH CH2), 2.88 (d, J = 5 Hz, 2H, CH CH2 ); 13 13C NMR (126 MHz, DMSO-d6) δ: 171.27, 162.45, 156.41, 134.78, 133.58, 132.39, 130.54, 129.29, 127.94, 126.97, 126.93, 115.52, 50.29, 40.95, 33.41; 19 19F NMR (417 MHz, DMSO-d6) δ: -58.02; HRMS: calcd for C 18 H 17 O2N3F3S, [M + H] + 396.09881, found 392.0979.

[0110]

[0111] II 13 : Yellow solid, yield 45%, melting point 99 - 100 °C. 1 1H NMR (500 MHz, DMSO-d6) δ: 9.33 (s, 1H, OH), 7.71 (d, J = 5 Hz, 2H, benzene H), 7.65 (d, J = 5 Hz, 2H, benzene H), 6.84–6.82 (m, 2H, benzene H), 6.60–6.58 (m, 2H, benzene H), 4.55 (s, 2H, SCH2), 4.16 (t, J = 15 Hz, 1H, CH CH2), 2.85 (d, J = 5 Hz, 2H, CH CH2 ); 13 13C NMR (126 MHz, DMSO-d6) δ: 171.05, 162.71, 156.42, 142.42, 130.50, 130.31, 127.91, 125.94, 125.91, 115.49, 50.27, 40.96, 35.42;19 F NMR(417MHz,DMSO-d6)δ: -60.88; HRMS: calcd for C 18 H 17 O2N3FS, [M + H] + 396.09881, found 392.0982.

[0112]

[0113] II 14 : Yellow solid, yield 51%, melting point 142 - 143 °C. 1 H NMR(500MHz,DMSO-d6)δ: 9.26(s, 1H, OH), 7.43–7.41(m, 2H, benzene H), 7.35–7.28(m, 3H, benzene H), 6.86–6.83(m, 2H, benzene H), 6.61–6.59(m, 2H, benzene H), 4.46(s, 2H, SCH2), 4.16(t, J = 15Hz, 1H, CH CH2), 2.87(d, J = 5Hz, 2H, CH CH2 ); 13 C NMR(101MHz,DMSO-d6)δ: 170.84, 162.95, 156.33, 137.08, 130.49, 129.44, 129.04, 128.21, 127.90, 115.45, 50.22, 40.93, 36.15; HRMS: calcd forC 17 H 18 O2N3S, [M + H] + 328.11142, found 328.1106.

[0114]

[0115] II 15 : Pale yellow solid, yield 44%, melting point 111 - 112 °C. 11H NMR (500 MHz, DMSO-d6) δ: 9.25 (s, 1H, OH), 7.69 (d, J = 5 Hz, 1H, benzene H), 7.55 (d, J = 10 Hz, 1H, benzene H), 7.42–7.40 (m, 1H, benzene H), 6.90–6.87 (m, 2H, benzene H), 6.62–6.60 (m, 2H, benzene H), 4.53 (s, 2H, SCH2), 4.17 (t, J = 15 Hz, 1H, CH CH2), 2.89–2.85 (m, 2H, CH CH2 ); 13 13C NMR (126 MHz, DMSO-d6) δ: 171.25, 162.36, 156.41, 134.81, 134.08, 133.67, 133.24, 130.56, 129.66, 128.10, 127.97, 115.51, 50.25, 40.92, 33.97; HRMS (ESI): calcd for C 17 H 15 Cl2N3O2S, [M+Na] + 418.01542, found: 418.01473.

[0116]

[0117] II 16 : Pale yellow solid, yield 48%, melting point 105 - 106 °C. 1 1H NMR (500 MHz, DMSO-d6) δ: 9.32 (s, 1H, OH), 7.93 (s, 1H, benzene H), 7.91–7.85 (m, 3H, benzene H), 7.58–7.56 (m, 1H, benzeneH), 7.52–7.50 (m, 2H, benzene H), 6.83–6.82 (m, 2H, benzene H), 6.58–6.56 (m, 2H, benzeneH), 4.64 (s, 2H, SCH2), 4.16 (t, J = 15 Hz, 1H, CH CH2), 2.85 (d, J = 5 Hz, 2H, CH CH2 ); 1313C NMR (126 MHz, DMSO-d6) δ: 170.90, 162.97, 156.37, 134.68, 133.21, 132.83, 130.53, 128.82, 128.21, 128.18, 128.11, 127.93, 127.43, 127.00, 126.80, 115.50, 50.26, 40.93, 36.57; HRMS: calcd for C 21 H 20 O2N3S, [M+H] + 378.12707, found 378.1260.

[0118]

[0119] II 17 : Yellow oil, yield 47%. 1 1H NMR (500 MHz, DMSO-d6) δ: 9.33 (s, 1H, OH), 7.59–7.57 (m, 1H, benzene H), 7.45–7.38 (m, 2H, benzene H), 6.88–6.86 (m, 2H, benzene H), 6.62–6.60 (m, 2H, benzene H), 4.46 (s, 2H, SCH2), 4.17 (t, J = 15 Hz, 1H, CH CH2), 2.87–2.85 (m, 2H, CH CH2 ); 13 13C NMR (126 MHz, DMSO-d6) δ: 171.24, 162.37, 156.44, 133.39, 130.54, 128.24, 127.92, 124.00, 123.88, 122.11, 122.03, 119.57, 119.38, 115.52, 50.27, 40.93, 29.67; 19 19F NMR (417 MHz, DMSO-d6) δ: -113.36; HRMS: calcd for C 17 H 16 O2N3BrFS, [M+H] + 424.01251, found 424.0116.

[0120] Bioactivity test method of the target compound

[0121] Bacterial antibacterial activity test

[0122] The turbidimetry method was used to preliminarily screen the activities of the target compounds against Xanthomonas oryzae pv. oryzae (Xoo), Xanthomonas axonopodis pv. citri (Xac), and Pseudomonas syringae pv. actinidiae (Psa) at a concentration of 50 μg / mL.

[0123] EC 50 Determination of value

[0124] According to the preliminary screening data, the method of serial dilution was used to set 5 concentration values for the target compounds with better activities, and further determine the bacterial inhibition rates of the target compounds with better activities. The calculation method of the inhibition rate was the same as above for calculating the inhibition rate.

[0125] Control test for citrus canker

[0126] Two-year-old new leaf citrus plants were selected for the experiment. The commercial drug thiodiazole copper was used as the positive control drug, and an equal amount of DMSO was used as the negative control. First, the leaves of citrus trees were washed with sterile water, and then a disposable sterilized syringe was used to puncture rectangular wounds of 3×3 on both sides of the leaves.

[0127] Protection activity test: Prepare a solution of the test compound or the positive control drug at 200 μg / mL, then immerse the filter paper in it for 1 h, and then evenly attach it to the wound and leave it for 24 h. After that, discard the drug-containing filter paper and replace it with a new filter paper soaked in the Xac suspension (OD 595 = 0.01) and attach it to the above wound again for 24 h.

[0128] Therapeutic activity test: First inoculate Xac, and then apply the drug. A total of 5 independent experiments were carried out. (The citrus plants were cultivated in an incubator with 16 h of light, a temperature of 28 °C, 8 h of darkness, a temperature of 25 °C, and a humidity of 95%). After 14 days of cultivation, calculate the chlorophyll content according to the kit, and calculate the control effect according to the chlorophyll. The method is as follows:

[0129] Determine the chlorophyll content of different treatment groups under the same culture conditions: Accurately weigh 0.1 g of leaves (cut each small hole), place them in a 2 mL centrifuge tube, add 1 mL of distilled water, grind them into a homogenate (50 Hz, 900 s), transfer them to a 15 mL centrifuge tube, add the extraction solution (95% anhydrous ethanol) to make the volume up to 10 mL, shake well, and let it stand in the dark at room temperature for 2 h. Take 200 μL of the supernatant and put it in a 96-well plate, and use an enzyme-linked immunosorbent assay (ELISA) reader to detect the absorbance at 663 nm and 645 nm. Calculate the chlorophyll a content, chlorophyll b content, total chlorophyll content, and inhibition rate according to the following formula.

[0130] Ca (mg / L) = 12.7 OD 663 –2.69 OD 645

[0131] Cb (mg / L) = 22.9 OD 645 –4.68 OD 663

[0132] Ct (mg / L) = Ca + Cb = 20.21 OD 663 +8.02 OD 645

[0133] Chlorophyll content (mg / g) = [Concentration (mg / L) × Total volume of extraction solution (mL)] / Total mass of leaves (g)

[0134] Where Ct, Cb, and Ca represent the total concentration of chlorophyll, the concentration of chlorophyll b, and the concentration of chlorophyll a, respectively.

[0135] Antibacterial activity data of the target compound

[0136] According to the above experimental procedures, the in vitro biological activities of all target compounds against Xanthomonas oryzae pv. oryzae (Xoo), Xanthomonas axonopodis pv. citri (Xac), and Pseudomonas syringae pv. actinidiae (Psa) were tested by the turbidimetry method, and the results are shown in Tables 1 - 4.

[0137] Table 1 Compounds I1 - I 15 Antibacterial test results against Xoo, Xac, and Psa at a concentration of 50 μg / mL a

[0138]

[0139]

[0140] "a" Each experiment was repeated three times.

[0141] Table 2 EC values of some target compounds in Series I against Xoo and Xac 50 Value a

[0142]

[0143]

[0144] "a" Each experiment was repeated three times. "-" indicates not measured.

[0145] Table 3 Compounds II1-II 17 Antibacterial test results against Xoo, Xac and Psa at a concentration of 50 μg / mL a

[0146]

[0147] "a" Each experiment was repeated three times.

[0148] Table 4 EC of some target compounds in Series II against Xoo and Xac 50 value a

[0149]

[0150]

[0151] "a" Each experiment was repeated three times. "-" means not measured.

[0152] As can be seen from Table 1 and Table 3, at a concentration of 50 μg / mL, most of the target compounds showed significant antibacterial activity against Xoo and Xac, with an activity above 90%. According to the preliminary antibacterial activity test results, compounds with better activity were selected for further activity screening against Xoo and Xac. As can be seen from Table 2, when R is dichlorosubstituted benzyl, the inhibitory effect of the target compounds on phytopathogenic bacteria can be improved. For example, compound I 11 (EC 50 = 2.3 μg / mL) had better antibacterial activity against Xac than compounds I1 (EC 50 = 5.8 μg / mL) and I2 (EC 50 = 3.5 μg / mL), and compound I 10 (EC 50 = 3.0 μg / mL) had better antibacterial activity against Xoo than compounds I1 (EC 50 = 14.0 μg / mL) and I2 (EC 50 = 11.8 μg / mL). When the R group is the same and M is phenyl, the inhibitory effect of the target compounds on Xoo and Xac increased significantly, such as II 11 <I5, II 15 <I 11 and II7<I3.

[0153] Table 5 Compound I 11 In vivo control effect against citrus bacterial canker at a concentration of 200 μg / mL

[0154]

[0155] Note: P represents protective activity, and C represents therapeutic activity; different lowercase letters indicate significant differences between treatment groups (P < 0.05).

[0156] As Figure 1 shown in Table 5, when compared with the leaves treated with only water (blank control), the CK treatment (negative control) caused obvious damage to citrus leaves; at a concentration of 200 μg / mL, the target compound I 11 showed good protective and therapeutic activities against citrus canker, which were 90.67% and 73.10% respectively, both superior to those of the commercial control agent bismerthiazol, which were 61.59% and 40.84%. Systematic analysis found that compound I 11 showed strong comprehensive activities in in vitro and in vivo tests, and such active compounds showed potential application value in inhibiting phytopathogenic bacteria.

Claims

1. An amino acid derivative containing 1,3,4-oxadiazole sulfide, characterized in that: Its structural formula is as follows: Wherein M is phenyl or 4-phenylethyl, and R is methyl, 2-naphthyl, benzyl or substituted benzyl.

2. The amino acid derivative containing 1,3,4-oxadiazole sulfide according to claim 1, characterized in that: The substitution position of the R-substituted benzyl group is single substitution at the ortho, meta or para position, and the substituent is methyl, methoxy, trifluoromethyl, trifluoromethoxy, fluorine, chlorine and bromine.

3. The amino acid derivative containing 1,3,4-oxadiazole sulfide according to claim 1, characterized in that: The substitution position of the R-substituted benzyl group is di-substitution at the ortho, meta or para position, and the substituent is fluorine, chlorine or bromine.

4. A method for preparing an amino acid derivative containing 1,3,4-oxadiazole sulfide according to any one of claims 1 to 3, characterized in that: The reaction formula is as follows:

5. Use of an amino acid derivative containing 1,3,4-oxadiazole sulfide as claimed in any one of claims 1 to 3 in the preparation of an agent for preventing and controlling plant bacterial diseases.

6. The use according to claim 5, characterized in that: The plant bacterial diseases are rice bacterial blight pathogen and citrus bacterial canker pathogen.

7. Use of an amino acid derivative containing 1,3,4-oxadiazole sulfide as claimed in any one of claims 1 to 3 in preventing and controlling bacterial diseases on citrus leaves.

Images