A pyruvate dehydrogenase e2 inhibitor and preparation method and application thereof

Abstract

The application discloses a pyruvate dehydrogenase E2 inhibitor and a preparation method thereof. The application also discloses a bactericide containing the pyruvate dehydrogenase E2 inhibitor. The application occupies the binding site of lipoic acid in the active cavity by designing an analogue of lipoic acid, so as to hinder the catalytic reaction and achieve the purpose of inhibiting the growth of organisms. Based on this, the application takes the pyruvate dehydrogenase system in microorganisms as a target, designs and synthesizes a novel and efficient pyruvate dehydrogenase E2 (PDHc-E2) inhibitor, which can be used for developing a novel and efficient bactericide and is widely applied to the prevention and treatment of bacterial brown spot bacteria of rice or bacterial leaf blight bacteria of rice.

Description

Technical Field

[0001] This invention relates to the field of chemical technology, specifically to a pyruvate dehydrogenase E2 inhibitor. Background Technology

[0002] Exploring and discovering pesticide active compounds with novel structures and targets is currently a focus of research in new pesticide creation. In biological metabolism, the pyruvate dehydrogenase complex (PDHc) catalyzes the conversion of pyruvate to acetyl-CoA, serving as a key enzyme connecting glycolysis and the citric acid cycle, and also a crucial enzyme in energy metabolism. Therefore, the pyruvate dehydrogenase complex is a target of significant agronomic importance, and the rational design of pesticide molecules targeting this target has high research value. PDHc is mainly composed of a highly integrated combination of three enzymes, including the pyruvate dehydrogenase E1 component (PDHc-E1 EC 1.2.4.1), dihydrolipoic acid transacetylase E2 (PDHc-E2, EC 2.3.1.12), and dihydrolipoic acid dehydrogenase E3 (PDHc-E3, EC 1.8.1.4).

[0003] Currently, existing patents (CN 106588887 B, CN 116332859 A, CN 116283794ACN108976214A) have modified the structure of the coenzyme thiamine pyrophosphate (ThDP) of PDHc-E1 enzyme, disclosing highly effective inhibitors of PDHc-E1 in microorganisms. Although the disclosed inhibitors are highly effective against PDHc-E1 in microorganisms, these inhibitors have complex structures, requiring more than three steps in their synthesis. Currently, there are no publicly reported inhibitors targeting PDHc-E2 in microorganisms. Summary of the Invention

[0004] The purpose of this invention is to solve the problem that there is no PDHc-E2 inhibitor in the prior art that acts on microorganisms, and to provide a pyruvate dehydrogenase E2 inhibitor, its preparation method and application.

[0005] To solve the above-mentioned technical problems, the present invention adopts the following technical solution: a pyruvate dehydrogenase E2 inhibitor, the chemical structural formula of which is shown in Formula I:

[0006]

[0007] Wherein, R is any one of CH3, Et, OCH3, Cl, Br, F, NH2, and C(CH3)3.

[0008] The present invention also provides a method for preparing the above-mentioned pyruvate dehydrogenase E2 inhibitor, wherein the compound shown in Formula II and the compound shown in Formula III are dissolved in an organic solvent and a catalyst is added to react to obtain the pyruvate dehydrogenase E2 inhibitor shown in Formula I.

[0009] The compound shown in Formula II is:

[0010]

[0011] The compound shown in Formula III is:

[0012]

[0013] Wherein, R is any one of CH3, Et, OCH3, Cl, Br, F, NH2, and C(CH3)3.

[0014] The chemical synthesis equation for the pyruvate dehydrogenase E2 inhibitor, as shown in Formula I, is attached. Figure 1 As shown.

[0015] Preferably, the molar ratio of the compound shown in Formula II to the compound shown in Formula III and the catalyst is 1:1 to 1.5:0.1 to 1.5.

[0016] Preferably, the organic solvent is one or more of N,N-dimethylformamide, dimethyl sulfoxide, tetrahydrofuran, acetone, acetonitrile, and toluene.

[0017] Preferably, the catalyst is one or more of sulfuric acid, hydrochloric acid, acetic acid, p-toluenesulfonic acid, phosphoric acid, formic acid, dicyclohexylcarbodiimide (DCC), 4-dimethylaminopyridine (DMAP), and N,N'-carbonyldiimidazole (CDI).

[0018] The present invention also provides a bactericide comprising the above-mentioned pyruvate dehydrogenase E2 inhibitor.

[0019] The present invention also provides the application of the above-mentioned pyruvate dehydrogenase E2 inhibitor or fungicide in the control of bacterial brown spot fungus or bacterial leaf blight fungus in rice.

[0020] The beneficial effects of this invention are as follows: This invention designs analogs of lipoic acid to occupy the binding sites of lipoic acid in the active cavity, thereby hindering the catalytic reaction and inhibiting biological growth. Based on this, this invention targets the pyruvate dehydrogenase system in microorganisms and designs and synthesizes novel, highly efficient pyruvate dehydrogenase E2 (PDHc-E2) inhibitors, which can be used to develop novel, highly efficient fungicides and widely applied to the control of bacterial brown spot or bacterial blight of rice. Attached Figure Description

[0021] Figure 1The chemical synthesis equation for the pyruvate dehydrogenase E2 inhibitor shown in Formula I is as follows:

[0022] Figure 2 A schematic diagram of the PDHc-E2 activity assay method. Detailed Implementation

[0023] The present invention will be further described below with reference to the accompanying drawings and specific embodiments.

[0024] Example 1: Preparation of PDHc-E2 Inhibitor 1

[0025] 1 mmol of lipoic acid and 1.2 mmol of phenol were dissolved in 6 mL of dimethyl sulfoxide solvent, and 0.1 mmol of sulfuric acid was added. The mixture was stirred at 80 °C for 24 h. After the reaction was complete, 50 mL of water was added, and a solid precipitated out upon stirring. The solid was filtered and dried to obtain a yellow solid, PDHc-E2 inhibitor 1. The chemical formula of PDHc-E2 inhibitor 1 is as follows:

[0026]

[0027] Its structural identification data are as follows:

[0028] 1 H NMR (CDCl3, 400MHz): δ (ppm) = 7.35 (t, J = 8.5Hz, 2H, Ar-H), 7.21 (t, J = 7.5Hz 1H, Ar-H), 7.06 (d, J = 8.5Hz, 2H, Ar-H), 3.65-3.50 (m, 1H, CH), 3.25 -3.05(m,2H,CH2),2.58(t,J=7.5Hz,2H,CH2),2.51-2.41(m,1H,CH2),1.98-1.87(m,1H,CH2),1.85-1.69(m,4H,CH2),1.65-1.50(m,2H,CH2); 13 C NMR (CDCl3, 400MHz): δ (ppm) = 171.8, 150.6, 129.4, 125.7, 121.5, 56.2, 40.2, 38.5, 34.6, 34.1, 28.6, 24.6.

[0029] Example 2: Preparation of PDHc-E2 Inhibitor 2

[0030] 1 mmol of lipoic acid and 1.2 mmol of p-methylphenol were dissolved in 6 mL of N,N-dimethylformamide solvent, and 0.01 mmol of sulfuric acid was added. The mixture was stirred at 80 °C for 24 h. After the reaction was complete, 50 mL of water was added, and a solid precipitated out upon stirring. The solid was filtered and dried to obtain a yellow solid, PDHc-E2 inhibitor 2. The chemical formula of PDHc-E2 inhibitor 2 is as follows:

[0031]

[0032] 1 H NMR (CDCl3, 400MHz): δ (ppm) = 7.35 (t, J = 8.5Hz, 4H, Ar-H), 3.65-3.50 (m, 1H, CH), 3.25-3.05 (m, 2H, CH2), 3.11 (s, 3H, CH3 ),2.61(t,J=7.5Hz,2H),2.51-2.41(m,1H,CH2),1.98-1.87(m,1H,CH2),1.85-1.69(m,4H,CH2),1.65-1.50(m,2H,CH2); 13 C NMR (CDCl3, 100MHz): δ (ppm) = 171.8, 149.6, 135.2, 129.7, 121.5, 56.3, 40.2, 38.5, 34.6, 34.1, 28.6, 24.6, 21.3.

[0033] Example 3: Preparation of PDHc-E2 Inhibitor 3

[0034] 1 mmol of lipoic acid and 1.2 mmol of m-methylphenol were dissolved in 6 mL of dimethyl sulfoxide solvent, and 0.1 mmol of p-toluenesulfonic acid was added. The mixture was stirred at 80 °C for 24 h. After the reaction was complete, 50 mL of water was added, and a solid precipitated out upon stirring. The solid was filtered and dried to obtain a yellow solid PDHc-E2 inhibitor 3. The chemical formula of PDHc-E2 inhibitor 3 is as follows:

[0035]

[0036] 1 H NMR (CDCl3, 400MHz): δ (ppm) = 7.36 (m, 2H, Ar-H), 7.12 (m, 2H, Ar-H), 3.60-3.55 (m, 1H, CH), 3.25-3.05 (m, 2H, CH2), 3.21 (s, 3H ,CH3),2.62(t,J=7.5Hz,2H),2.51-2.41(m,1H,CH2),1.98-1.87(m,1H,CH2),1.85-1.69(m,4H,CH2),1.65-1.50(m,2H,CH2); 13 C NMR (CDCl3, 100MHz): δ (ppm) = 172.2, 151.2, 138.3, 129.3, 125.9, 122.3, 118.6, 56.6, 40.5, 38.6, 34.7, 34.2, 28.7, 24.5, 21.4.

[0037] Example 4: Preparation of PDHc-E2 Inhibitor 4

[0038] 1 mmol of lipoic acid and 1.2 mmol of m-methylphenol were dissolved in 6 mL of dimethyl sulfoxide solvent. 1.1 mmol of dicyclohexylcarbodiimide was added, and the mixture was stirred at 80 °C for 24 h. After the reaction was complete, 50 mL of water was added, and a solid precipitated out upon stirring. The solid was filtered and dried to obtain a yellow solid, PDHc-E2 inhibitor 4. The chemical formula of PDHc-E2 inhibitor 4 is as follows:

[0039]

[0040] 1 H NMR (CDCl3, 400MHz): δ (ppm) = 7.40 (m, 2H, Ar-H), 7.20 (m, 2H, Ar-H), 3.61-3.56 (m, 1H, CH), 3.24-3.04 (m, 2H, CH2), 3.22 (s, 3H ,CH3),2.62(t,J=7.5Hz,2H),2.51-2.41(m,1H,CH2),1.99-1.88(m,1H,CH2),1.86-1.70(m,4H,CH2),1.66-1.50(m,2H,CH2); 13 C NMR (CDCl3, 100MHz): δ (ppm) = 172.4, 150.7, 130.1, 131.2, 125.1, 124.1, 122.4, 56.5, 40.8, 38.8, 34.3, 34.1, 28.9, 24.6, 15.8.

[0041] Example 5: Preparation of PDHc-E2 Inhibitor 5

[0042] 1 mmol of lipoic acid and 1.2 mmol of p-methoxyphenol were dissolved in 6 mL of dimethyl sulfoxide, and 1.1 mmol of N,N'-carbonyldiimidazole was added. The mixture was stirred at 80 °C for 24 h. After the reaction was complete, 50 mL of water was added, and a solid precipitated out upon stirring. The solid was filtered and dried to obtain a yellow solid, PDHc-E2 inhibitor 5. The chemical formula of PDHc-E2 inhibitor 5 is as follows:

[0043]

[0044] 1H NMR (CDCl3, 400MHz): δ (ppm) = 6.99 (dd, J = 8.5, 8.7Hz, 4H, Ar-H), 3.60-3.51 (m, 1H, CH), 3.24-3.15 (m, 2H, CH2), 3.81 (s, 3H, O CH3),2.63(t,J=7.5Hz,2H),2.48-2.44(m,1H,CH2),1.88-1.77(m,1H,CH2),1.86-1.70(m,4H,CH2),1.65-1.50(m,2H,CH2); 13 C NMR (CDCl3, 100MHz): δ (ppm) = 172.6, 156.4, 143.2, 126.6, 114.5, 56.3, 55.3, 40.1, 38.4, 34.5, 33.6, 28.5, 24.6.

[0045] Example 6: Preparation of PDHc-E2 Inhibitor 6

[0046] 1 mmol of lipoic acid and 1.2 mmol of p-tert-butylphenol were dissolved in 6 mL of dimethyl sulfoxide. 1.1 mmol of dicyclohexylcarbodiimide and 0.1 mmol of 4-dimethylaminopyridine (DMAP) were added, and the mixture was stirred at 80 °C for 24 h. After the reaction was complete, 50 mL of water was added, and a solid precipitated out upon stirring. The solid was filtered and dried to obtain a yellow solid, PDHc-E2 inhibitor 6. The chemical formula of PDHc-E2 inhibitor 6 is as follows:

[0047]

[0048] 1 H NMR (CDCl3, 400MHz): δ (ppm) = 7.56 (d, J = 8.5Hz, 2H, Ar-H), 7.21 (d, J = 8.7Hz, 2H, Ar-H), 3.54-3.45 (m, 1H, CH), 3.25-3.18 (m, 2H, CH2), 2.6 3(t,J=7.5Hz,2H,CH2),2.45-2.38(m,1H,CH2),1.87-1.70(m,1H,CH2),1.78-1.72(m,4H,CH2),1.54-1.48(m,2H,CH2),,1.35(s,9H,CH3); 13 C NMR (CDCl3, 100MHz): δ (ppm) = 172.4, 148.8, 148.3, 125.6, 121.5, 56.6, 55.5, 40.2, 38.6, 34.6, 33.5, 28.6, 24.6.

[0049] The PDHc-E2 inhibitors 7-14 in Examples 7-14 could all be prepared according to the preparation method in Example 6, and the structural identification data are as follows:

[0050] Example 7: Preparation of PDHc-E2 Inhibitor 7

[0051]

[0052] 1 H NMR (CDCl3, 400MHz): δ (ppm) = 7.06 (d, J = 8.8Hz, 2H, Ar-H), 6.74 (d, J = 9.7Hz, 2H, Ar-H), 6.27 (s, 2H, NH2), 3.15-3.01 (m, 1H, CH), 2.98-2.7 8(m,2H,CH2),2.43(t,J=7.5Hz,2H,CH2),2.34-2.35(m,1H,CH2),1.77-1.65(m,1H,CH2),1.51-1.48(m,4H,CH2),1.40-1.38(m,2H,CH2); 13 C NMR (CDCl3, 100MHz): δ (ppm) = 172.3, 145.8, 141.3, 122.6, 115.4, 56.4, 55.3, 40.1, 38.3, 34.3, 33.4, 28.2, 24.6.

[0053] Example 8: Preparation of PDHc-E2 Inhibitor 8

[0054]

[0055] 1 H NMR (CDCl3, 400MHz): δ (ppm) = 7.60 (d, J = 6.5Hz, 1H, Ar-H), 7.33 (t, J = 8.0Hz, 1H, Ar-H), 7.16-7.10 (m, 2H, Ar-H), 3.64-3.56 (m, 1H, CH), 3.25-3. 05(m,2H,CH2),2.67-2.62(t,J=7.0Hz,2H,CH2),2.52-2.44(m,1H,CH2),1.97-1.89(m,1H,CH2),1.88-1.71(m,4H,CH2),1.66-1.55(m,2H,CH2); 13 C NMR (CDCl3, 100MHz): δ (ppm) = 171.2, 148.4, 133.6, 128.7, 127.5, 124.0, 116.4, 56.5, 40.5, 38.8, 35.1, 34.1, 28.9, 24.7.

[0056] Example 9: Preparation of PDHc-E2 Inhibitor 9

[0057]

[0058] 1 H NMR (CDCl3, 400MHz): δ (ppm) = 7.62 (d, J = 6.5Hz, 2H, Ar-H), 7.23 (d, J = 7.8Hz, 2H, Ar-H), 3.65-3.57 (m, 1H, CH), 3.20-3.10 (m, 2H, CH2 ),2.60-2.56(t,J=7.0Hz,2H,CH2),2.50-2.42(m,1H,CH2),1.96-1.88(m,1H,CH2),1.83-1.70(m,4H,CH2),1.65-1.56(m,2H,CH2); 13 C NMR (CDCl3, 100MHz): δ (ppm) = 172.6, 150.4, 132.9, 123.6, 119.6, 56.3, 40.2, 38.5, 35.1, 34.6, 28.6, 24.6.

[0059] Example 10: Preparation of PDHc-E2 Inhibitor 10

[0060]

[0061] 1 H NMR (CDCl3, 400MHz): δ (ppm) = 7.56 (dd, J = 6.5, 7.3Hz, 4H, Ar-H), 3.68-3.60 (m, 1H, CH), 3.23-3.12 (m, 2H, CH2), 2.65-2. 59(t,J=7.0Hz,2H,CH2),2.52-2.44(m,1H,CH2),1.97-1.84(m,1H,CH2),1.70-1.68(m,4H,CH2),1.65-1.56(m,2H,CH2); 13 C NMR (CDCl3, 100MHz): δ (ppm) = 172.3, 149.4, 131.9, 130.2, 123.6, 56.2, 40.1, 38.6, 35.3, 34.5, 28.5, 24.4.

[0062] Example 11 Preparation of PDHc-E2 Inhibitor 11

[0063]

[0064] 1H NMR (CDCl3, 400MHz): δ (ppm) = 7.21-7.27 (m, 4H, Ar-H), 3.70-3.65 (m, 1H, CH), 3.26-3.18 (m, 2H, CH2), 2.67-2.60 (t ,J=7.0Hz,2H,CH2),2.54-2.48(m,1H,CH2),1.97-1.84(m,1H,CH2),1.70-1.68(m,4H,CH2),1.65-1.56(m,2H,CH2); 13 C NMR (CDCl3, 100MHz): δ (ppm) = 172.3, 159.4, 146.6, 123.6, 116.2, 56.3, 40.2, 38.7, 35.4, 34.7, 28.6, 24.7.

[0065] Example 12 Preparation of PDHc-E2 Inhibitor 12

[0066]

[0067] 1 H NMR (CDCl3, 400MHz): δ (ppm) = 7.25 (t, J = 7.6Hz, 4H, Ar-H), 3.65-3.50 (m, 1H, CH), 3.20-3.11 (m, 2H, CH2), 2.60 (t, J = 7.5Hz, 2H, CH2), 2.8 8(s,3H,CH3),2.48-2.40(m,1H,CH2),1.97-1.87(m,1H,CH2),1.85-1.69(m,4H,CH2),1.65-1.50(m,2H,CH2);1.25(t,J=5.2Hz,3H,CH3); 13 C NMR (CDCl3, 100MHz): δ (ppm) = 171.9, 149.8, 141.2, 129.6, 121.8, 56.2, 40.3, 38.6, 34.5, 33.9, 28.3, 24.4, 28.2, 4.6.

[0068] Example 13 Preparation of PDHc-E2 Inhibitor 13

[0069]

[0070] 1H NMR (CDCl3, 400MHz): δ (ppm) = 7.69 (d, J = 8.6Hz, 2H, Ar-H), 7.21 (d, J = 8.8Hz, 2H, Ar-H), 3.65-3.55 (m, 1H, CH), 3.24-3.07 (m, 2H, C H2),2.62(t,J=7.5Hz,2H,CH2),2.52-2.43(m,1H,CH2),1.97-1.87(m,1H,CH2),1.83-1.768(m,4H,CH2),1.63-1.50(m,2H,CH2); 13 CNMR (CDCl3, 400MHz): δ (ppm) = 171.1, 154.0, 133.7, 122.8, 118.3, 109.8, 56.3, 40.3, 38.6, 34.6, 34.2, 28.7, 24.5.

[0071] Example 14 Preparation of PDHc-E2 Inhibitor 14

[0072]

[0073] 1 H NMR (CDCl3, 500MHz): δ (ppm) = 8.32-8.20 (d, J = 9.5Hz, 2H, Ar-H), 7.30-7.25 (d, J = 9.0Hz, 2H, Ar-H), 3.65-3.55 (m J=6.5Hz,1H,CH),3.25-3.07(m,2H,CH2),2.66-2.59(t,J=7.5Hz,2H,CH2),2.53-2.4 3(m,1H,CH2),1.97-1.89(m,1H,CH2),1.86-1.70(m,4H,CH2),1.64-1.50(m,2H,CH2); 13 C NMR (CDCl3, 400MHz): δ (ppm) = 171.0, 155.6, 145.4, 125.2, 22.5, 56.3, 40.3, 38.6, 34.6, 34.2, 28.7, 24.5.

[0074] Example 15

[0075] In this embodiment, the PDHc-E2 inhibitors 1-14 prepared in Examples 1-14 were used to conduct PDHc-E2 inhibitory activity tests and agricultural bacteria activity tests.

[0076] 1. PDHc-E2 inhibitory activity test experiment

[0077] Using PDHc-E2 in *E. coli* as a model, the 2,6-DCIP method was used to determine the activities of the PDHc-E2 inhibitors 1-14 prepared in Examples 1-14 against PDHc-E2. 2,6-DCIP acts as an electron acceptor, and enzyme activity was represented by measuring the reduction of 2,6-DCIP by hydroxyethyl-ThDP (a decrease in light absorption at 600 nm). Figure 2 The experimental results are shown in Table 1.

[0078] 2. Experiment on the activity of agricultural bacteria

[0079] Experimental materials: Bacterial brown spot fungus of rice, bacterial blight fungus of rice

[0080] Experimental Methods: The antibacterial effect of the compound was mainly determined using the bacterial plate count method. The specific steps were as follows: first, 10 μL of bacterial suspension was diluted in 90 μL of physiological saline, and then the bacterial suspension was diluted 10-fold using the 10-fold dilution method to a final concentration of 10 μL. -7 cfu / ml; then pipette from 10 -1 cfu / mL, 10 -2 cfu / mL, 10 -3 cfu / mL, 10 -4 cfu / mL, 10 -5 cfu / mL, 10 -6 cfu / mL, 10 -7 Three different concentrations of bacterial suspension were prepared and dropped onto plates (10 μL each for three different concentrations: *Bacillus thuringiensis* (rice bacterial brown streak) on LB plates, and *Bacillus thuringiensis* (rice bacterial blight) on NA plates). Each treatment was repeated three times. After the plates dried, they were incubated at 3°C ​​for 24 hours. Plates with colony counts between 10 and 200 were used for bacterial counting to determine the original bacterial load and thus the bactericidal activity of the compound. Agricultural streptomycin sulfate was used as a control group.

[0081] Calculation formula:

[0082] Total viable bacteria count per milliliter of reaction solution = average colony count at the same dilution × dilution factor × 10

[0083] Antibacterial inhibition rate = (Number of bacteria treated without compound - Number of bacteria treated with compound or positive control agent) / Number of bacteria treated without compound × 100%.

[0084] Table 1. Bioactivity of PDHc-E2 inhibitors 1-14 prepared in Examples 1-14

[0085]

[0086]

[0087] The data in Table 1 show that the PDHc-E2 inhibitors 1-14 (i.e., PDHc-E2 inhibitors of general formula I) prepared in Examples 1-14 of this invention not only have superior inhibitory activity against PDHc-E2 in Escherichia coli, but also exhibit excellent bactericidal activity. They can be used to control bacterial brown spot and bacterial blight of rice. The control effect of some inhibitors on bacteria is comparable to or better than that of the control commercial fungicides.

[0088] The specification and drawings of this invention are intended to be illustrative rather than restrictive. Based on this invention, those skilled in the art can make substitutions and modifications to some of the technical features without creative effort, and all such modifications are within the scope of protection of this invention.

Claims

1. A pyruvate dehydrogenase E2 inhibitor, characterized in that, The chemical structural formula of the pyruvate dehydrogenase E2 inhibitor is shown in Formula I: Wherein, R is any one of CH3, Et, OCH3, Cl, Br, F, NH2, and C(CH3)3.

2. The method for preparing the pyruvate dehydrogenase E2 inhibitor as described in claim 1, characterized in that, The compounds shown in Formula II and Formula III were dissolved in an organic solvent and reacted with a catalyst to obtain the pyruvate dehydrogenase E2 inhibitor shown in Formula I. The compound shown in Formula II is: The compound shown in Formula III is: Wherein, R is any one of CH3, Et, OCH3, Cl, Br, F, NH2, and C(CH3)3.

3. The preparation method according to claim 2, characterized in that, The molar ratio of the compound shown in Formula II to the compound shown in Formula III and the catalyst is 1:1 to 1.5:0.1 to 1.

5.

4. The preparation method according to claim 2, characterized in that, The organic solvent is one or more of N,N-dimethylformamide, dimethyl sulfoxide, tetrahydrofuran, acetone, acetonitrile, and toluene.

5. The preparation method according to claim 2, characterized in that, The catalyst is one or more of sulfuric acid, hydrochloric acid, acetic acid, p-toluenesulfonic acid, phosphoric acid, formic acid, dicyclohexylcarbodiimide (DCC), 4-dimethylaminopyridine (DMAP), and N,N'-carbonyldiimidazole (CDI).

6. A bactericide, characterized in that, It contains the pyruvate dehydrogenase E2 inhibitor as described in claim 1.

7. The application of the pyruvate dehydrogenase E2 inhibitor as described in claim 1 or the fungicide as described in claim 6 in the control of bacterial brown spot fungus or bacterial leaf blight fungus of rice.

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