Novel borate bactericide and preparation method thereof

Abstract

The invention provides a series of novel borate compounds as shown in a formula I and a preparation method thereof. The compound has the effects of remarkably inhibiting conidium germination, bud tube growth or appressorium formation of fungi and oomycetes, effectively preventing pathogenic bacteria from infecting host plants and preventing and treating important plant diseases such as rice blast, mango anthracnose, wheat scab, wheat powdery mildew, potato late blight and phytophthora capsici.

Description

Technical Field

[0001] This invention belongs to the field of fungicide technology, specifically relating to borate ester compounds that can inhibit spore germination and appressorium formation of pathogenic fungi and oomycetes, their preparation methods, and their uses in the prevention and control of plant diseases caused by pathogenic fungi and oomycetes. Background Technology

[0002] It is estimated that over 80% of plant diseases are caused by fungi and oomycetes. A single plant can be affected by several or even dozens of different fungi and oomycetes causing diseases. For example, rice diseases such as sheath blight, rice blast, rice false smut, sesame leaf spot, and bakanae disease; wheat diseases such as Fusarium head blight, powdery mildew, stripe rust, stem rust, leaf rust, and root rot; and corn diseases such as large leaf spot, small leaf spot, stem base rot, rust, sheath blight, Curvularia leaf spot, head smut, and powdery mildew are all caused by fungi. Potato late blight, soybean Phytophthora blight, pepper Phytophthora blight, grape downy mildew, and cucumber downy mildew are caused by oomycetes.

[0003] Due to their economic and efficient nature, chemical fungicides are the preferred method of agricultural pest control. From 1990 to 2018, global usage of agricultural fungicides increased from 393 million kg to 530 million kg. Currently, commonly used fungicides in chemical control include boscalid, cyazofamid, chlorothalonil, thiophanate-methyl, carbendazim, azoxystrobin, pyraclostrobin, prochloraz, and tricyclazole. Most of these fungicides were screened based on their target organisms, and they have varying degrees of toxicity to non-target organisms in the farmland environment. Furthermore, they exhibit similar and singular modes of action, field resistance development, and severe cross-resistance issues among fungicides of the same class, leading to poor control efficacy. Therefore, the development of low-toxicity, highly efficient, and environmentally friendly fungicides is an urgent need for safe production.

[0004] Most plant pathogenic fungi and oomycetes spread primarily through asexual spores in the field. For example, when *Pyrospora oryzae* and *Anthracnose* infect plants, spores adhere to the plant surface and germinate into germ tubes. Appressoria then form at the tips of these germ tubes, and under significant turgor pressure, infection nails differentiate from the base of the appressoria, invading the plant tissue and causing disease. However, currently, there are very few fungicides on the pesticide market that specifically inhibit spore germination and appressoria formation; only tricyclazole prevents disease by inhibiting the maturation of pathogen appressoria. Therefore, developing inhibitors targeting pathogen spore germination and appressoria formation could provide a new avenue for the development of novel fungicides.

[0005] Aryl heterocyclic borate esters and their derivatives have long been used as molecular building blocks in organic synthesis, exhibiting a variety of bioactivities applicable in medicine due to their unique structural features. Examples include novel antitumor drugs developed targeting proteasome inhibitors and drugs used to treat inflammatory bowel disease. However, there are no reports of these aryl heterocyclic borate esters being used to control diseases caused by fungi and oomycetes in crops. Summary of the Invention

[0006] This invention provides novel aryl heterocyclic borate esters that significantly inhibit the germination of conidia and the formation of appressorium by *Pyrrosia oryzae*, exhibiting significant preventative and curative effects against pathogens such as rice blast. Furthermore, this series of compounds also demonstrates significant control effects against various other plant pathogenic fungi and oomycetes.

[0007] The technical solution of the present invention is as follows:

[0008] The compounds represented by Formula I, their stereoisomers, racemates, pharmaceutically acceptable salts, or solvates:

[0009]

[0010] in, R1 and R2, together with their two attached O atoms and B, constitute an unsubstituted or optionally substituted group consisting of one, two or more Ra groups: a 5-12 membered heterocyclic group or a benzo5-12 membered heterocyclic group; wherein Ra is selected from =O, C 1-12 Alkyl or halogenated C 1-12 alkyl;

[0011] R3 is selected from H or R 33 R 33 Selected from -C=NX-Rb; X is selected from NH or O; Rb is selected from C 1-12 Alkyl, Halogenated C 1-12 Alkyl, C 6-12 Aryl, 5-12 heteroaryl, -C 1-12 Alkyl-C 6-12 Aryl, -C 1-12 Alkyl-5-12-membered heteroaryl, -CO-C 1-12 Alkyl, -CO-C 6-12 Aryl, -CO-5-12 heteroaryl, -S(O)2-C 6-12 Aryl-C 1-12 Alkyl or -S(O)2-5-12-membered heteroaryl-C 1-12 alkyl;

[0012] R4 and R5 may be the same or different, and are independently selected from H, CN, halogens, and C. 1-12 Alkyl, Halogenated C 1-12 Alkyl, C1-12 Alkoxy, halogenated C 1-12 Alkoxy, -OC 6-12 Aryl or -O-5-12 heteroaryl; the -OC 6-12 C in aryl and -O-5-12-membered heteroaryl 6-12 The aryl group and the 5-12 heteroaryl group are independently unsubstituted, or optionally substituted by one, two or more Rc groups; said Rc group is selected from CN, halogen, C. 1-12 Alkyl, C 1-12 Alkyl groups, -COOC 1-12 Alkyl, -N(C) 1-12 alkyl)2 or -NHC 1-12 alkyl.

[0013] According to an embodiment of the present invention, R1 and R2 together with their two attached O atoms constitute unsubstituted or optionally substituted groups with one, two or more Ra: 5-8 membered heterocyclic groups or benzo5-6 membered heterocyclic groups; wherein Ra is selected from =O, C 1-6 Alkyl or halogenated C 1-6 alkyl.

[0014] In some embodiments of the present invention R1 and R2, together with the two O atoms attached to them and B, constitute an unsubstituted or optionally substituted group consisting of one, two or more Ra groups: a 5-8 membered heterocyclic group or a benzo5-8 membered heterocyclic group; wherein Ra is selected from =O, C 1-6 Alkyl or halogenated C 1-6 Alkyl group; the 5-8 membered heterocyclic group contains B and O, and further contains one or both of N or O; when N is present, Ra is substituted on N or on a carbon atom.

[0015] According to an embodiment of the present invention, The following groups are indicated to be unsubstituted or optionally substituted by one, two or more Ra atoms, together with R1 and R2 and the two O atoms attached to them and B:

[0016]

[0017] Ra is selected from =O, methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, or trifluoromethyl.

[0018] In some embodiments of the present invention This indicates that R1 and R2, together with the two O atoms attached to them and B, form the following groups:

[0019] Ra is selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, or trifluoromethyl.

[0020] According to an embodiment of the present invention, R3 is selected from H or R 33 R 33 Selected from -C=NX-Rb; X is selected from NH or O; Rb is selected from C 1-6 Alkyl, C 6-12 Aryl, 5-12 heteroaryl, -C 1-6 Alkyl-C 6-12 Aryl, -C 1-6 Alkyl-5-12-membered heteroaryl, -CO-C 1-6 Alkyl, -CO-C 6-12 Aryl, -CO-5-12 heteroaryl, -S(O)2-C 6-12 Aryl-C 1-6 Alkyl or -S(O)2-5-12-membered heteroaryl-C 1-6 alkyl.

[0021] According to an embodiment of the present invention, R4 and R5 may be the same or different, and are independently selected from H, CN, halogens, and C. 1-6 Alkyl, C 1-6 Alkoxy, -OC 6-12 Aryl or -O-5-12 heteroaryl; the -OC 6-12 C in aryl and -O-5-12-membered heteroaryl 6-12 The aryl group and the 5-12 heteroaryl group are independently unsubstituted, or optionally substituted by one, two or more Rc groups; said Rc group is selected from CN, halogen, C. 1-6 Alkyl, C 1-6 Alkyl groups, -COOC 1-6 Alkyl, -N(C) 1-6 alkyl)2 or -NHC 1-6 alkyl.

[0022] According to an embodiment of the present invention, the compound represented by Formula I is selected from the structures represented by Formula A, or Formula B, or Formula C:

[0023]

[0024] in, and R 33 It has the definition as described above;

[0025] In formula A, R 31 and R 41 They may be the same or different, and are independently selected from H, CN, halogens, and C. 1-6 Alkyl or C 1-6 Alkoxy; and R 31 and R41 Not both H;

[0026] In formula B, R 32 Selected from -OC 6-12 Aryl or -O-5-12 heteroaryl; the -OC 6-12 C in aryl and -O-5-12-membered heteroaryl 6-12 The aryl group and the 5-12 heteroaryl group are independently unsubstituted, or optionally substituted by one, two, or three Rc groups; said Rc groups are selected from CN, halogens, C. 1-6 Alkyl, C 1-6 Alkyl groups, -COOC 1-6 Alkyl, -N(C) 1-6 alkyl)2 or -NHC 1-6 alkyl;

[0027] In formula C, R 42 and R 51 Whether the same or different, they are independently selected from CN, halogen, and C. 1-6 Alkyl or halogenated C 1-6 alkyl.

[0028] According to an embodiment of the present invention, in formula A, This indicates that R1 and R2, together with the two O atoms attached to them and B, form the following groups: Ra may be the same as or different from each other, and are independently selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, or trifluoromethyl; R 31 The 4- or 5-substituent is attached to benzothiophene; R 41 It is a substituent at the 7-position of benzothiophene;

[0029] R 31 Selected from CN, F, Cl, methyl, ethyl, or methoxy;

[0030] R 41 Selected from H, F, Cl or methoxy.

[0031] According to an embodiment of the present invention, in formula B, This indicates that R1 and R2, together with the two O atoms attached to them and B, form the following groups: Ra may be the same or different, and is independently selected from methyl, ethyl, n-propyl, isopropyl, or n-butyl.

[0032] According to an embodiment of the present invention, in formula B, R 32 Selected from -O-phenyl, -O-1,3-benzoxyl, or -O-pyridyl; wherein the phenyl, 1,3-benzoxyl, or pyridyl group is independently unsubstituted, or optionally substituted by one, two, or more Rc groups; wherein the Rc group is selected from CN, F, Cl, C.1-3 Alkyl, C 1-3 Alkyl groups, -COOC 1-3 Alkyl, -N(C) 1-3 alkyl)2 or -NHC 1-6 alkyl.

[0033] According to an embodiment of the present invention, in formula B, R 32 Substituents at positions 4, 5, 6, or 7.

[0034] According to an embodiment of the present invention, in formula B, when R 32 When selected from -O-1,3-benzoxyl groups, it is

[0035]

[0036] According to an embodiment of the present invention, in formula B, when R 32 When selected from -O-pyridyl, it is 2-pyridoxy.

[0037] According to an embodiment of the present invention, in formula C, This indicates that R1 and R2, together with the two O atoms attached to them and B, form the following groups: Ra may be the same or different, and is independently selected from methyl, ethyl, n-propyl, isopropyl, n-butyl or tert-butyl.

[0038] According to an embodiment of the present invention, in formula C, R 33 Selected from -C=NX-Rb; X is selected from NH or O; Rb is selected from C 1-6 Alkyl, phenyl, pyridyl, -C 1-6 Alkyl-phenyl, -C 1-6 alkyl-pyridyl, -CO-C 1-6 Alkyl, -CO-phenyl, -CO-pyridyl, -S(O)2-phenyl-C 1-6 Alkyl or -S(O)2-pyridyl-C 1-6 alkyl.

[0039] According to an embodiment of the present invention, in formula C, R 42 and R 51 They may be the same or different, and are selected independently from halogens, such as F or Cl.

[0040] According to an embodiment of the present invention, in formula C, R 42 and R 51 The substituents are at positions 5 and 7, respectively.

[0041] According to an embodiment of the present invention, in formula C, R 42 and R 51 The substituents are at positions 5 and 7, respectively, and are both Cl.

[0042] According to an exemplary embodiment of the present invention, Formula A is selected from compounds defined by the following groups, including their stereoisomers, racemates, pharmaceutically acceptable salts, or solvates:

[0043]

[0044]

[0045]

[0046]

[0047] Formula B is selected from compounds defined by the following groups, their stereoisomers, racemates, pharmaceutically acceptable salts, or solvates:

[0048]

[0049]

[0050]

[0051]

[0052] Formula C is selected from compounds defined by the following groups, their stereoisomers, racemates, pharmaceutically acceptable salts, or solvates:

[0053]

[0054]

[0055] The present invention also provides a method for preparing the compound represented by Formula I as described above, comprising the following steps:

[0056]

[0057] Among them, R1, R2, R3, R4 and R5 have the definitions described above;

[0058] Compound Ia reacts with Ib to give the compound shown in Formula I.

[0059] According to embodiments of the present invention, the compounds represented by formula A, formula B, or formula C are prepared by the following method:

[0060] The compound shown in Formula A was prepared using general synthetic route I:

[0061]

[0062] Sodium ethoxide or cesium carbonate is placed in a reaction flask, a solvent is added, and compound GA-0 is added while stirring. After no more bubbles are produced, bromoacetaldehyde diethanol is slowly added to react and compound GA-1 is obtained.

[0063] Polyphosphoric acid was placed in a reaction flask, a solvent was added, and the mixture was stirred to dissolve it. Then, the dissolved compound GA-1 was added to react and compound GA-2 was obtained.

[0064] Compound GA-2 was placed in a reaction flask, ultra-dry tetrahydrofuran was added, the mixture was cooled to -78°C, then n-butyllithium solution was added dropwise, and the reaction was stirred at -78°C. Triisopropyl borate was then added dropwise, and the reaction was continued at -78°C to obtain compound GA-3.

[0065] Compound GA-3 was placed in a reaction flask, a solvent was added, and compound GA-4 was added under stirring to react and obtain compound A.

[0066] The compound shown in Formula B was prepared using general synthetic route II:

[0067]

[0068] The base was placed in a reaction flask, a solvent was added, and compound GB-0 was added while stirring. After no more bubbles were produced, bromoacetaldehyde diethanol condensation was slowly added to react and compound GB-1 was obtained.

[0069] Polyphosphoric acid was placed in a reaction flask, a solvent was added, and the mixture was stirred to dissolve it. Then, the dissolved compound GB-1 was added to react and compound GB-2 was obtained.

[0070] Compounds GB-2 and R 32 H, inorganic base, cuprous iodide and solvent were placed in a reaction flask and heated under reflux to give compound GB-3;

[0071] Compound GB-3 was placed in a reaction flask, cooled to -78°C, and n-butyllithium solution was added dropwise. The reaction was stirred while maintaining the temperature at -78°C. Then, triisopropyl borate was added dropwise, and the reaction was continued with stirring at -78°C to obtain compound GB-4.

[0072] Compound GB-4 was placed in a reaction flask, a solvent was added, and compound GB-5 was added under stirring to react and obtain the compound shown in formula B.

[0073]

[0074] The compound shown in formula C was prepared using synthetic route III:

[0075]

[0076] The base was placed in a reaction flask, a solvent was added, and compound GC-0 was added while stirring. After no more bubbles were produced, bromoacetaldehyde diethanol condensation was slowly added to react and compound GC-1 was obtained.

[0077] Polyphosphoric acid was placed in a reaction flask, a solvent was added, and the mixture was stirred to dissolve it. Then, the dissolved compound GC-1 was added to react and compound GC-2 was obtained.

[0078] Compound GC-2 was placed in a reaction flask, a solvent was added, and after cooling to 0°C, a chloride salt was slowly added. The reaction was carried out while maintaining 0°C and stirring. 1,1-Dichlorodimethyl ether was added dropwise to give compound GC-3.

[0079] Compound GC-3 was placed in a reaction flask, a solvent was added, and ammonium chloride was added under stirring to reflux and react to obtain compound GC-4.

[0080] Compound GC-4 was placed in a reaction flask, a solvent was added, the mixture was cooled to -78°C, a solution of n-butyllithium was added dropwise, and the mixture was stirred at -78°C. Then, triisopropyl borate was added dropwise, and the mixture was stirred at -78°C to obtain compound GC-5.

[0081] Compound GC-5 was placed in a reaction flask, a solvent was added, and compound GC-6' was added under stirring to react and obtain compound GC-6.

[0082] Compound GC-6 was placed in a reaction flask, a solvent was added, and compound GC-7 was added while stirring. The mixture was then brought to room temperature to give compound C.

[0083] Among them, X, Rb, R1, R2, R 31 R 32 R 33 R 41 R 42 and R 51 It has the definition described above.

[0084] The present invention also provides the use of the compounds of Formula I, their isomers, pharmaceutically acceptable salts or solvates as bactericides.

[0085] According to an embodiment of the present invention, the fungicide is used to inhibit the germination of fungal and oomycete spores and the formation of appressoriums, as well as to prevent and control plant diseases caused by fungi and oomycetes.

[0086] According to an embodiment of the present invention, the fungus is at least one of *Pyrrosia lingua*, *Anthracis*, *Fusarium graminearum*, *Phytophthora indicum*, and *Phytophthora indicum*.

[0087] According to embodiments of the present invention, the plant diseases caused by the fungi and oomycetes are selected from the following: rice sheath blight, rice blast, rice false smut, sesame spot, and bakanae disease; wheat scab, powdery mildew, stripe rust, stem rust, leaf rust, root rot, and sheath blight; corn large leaf spot, small leaf spot, anthracnose, stem base rot, rust, sheath blight, Curvularia leaf spot, common smut, and powdery mildew; mango anthracnose, potato late blight, strawberry gray mold, soybean Phytophthora blight, pepper Phytophthora blight, grape downy mildew, and cucumber downy mildew.

[0088] The present invention also provides a bactericidal composition comprising: a compound of formula I, an isomer thereof, a pharmaceutically acceptable salt thereof, or a solvate thereof.

[0089] Beneficial effects

[0090] The borate ester compounds of the present invention have a significant inhibitory effect on the germination and appressorium formation of various plant pathogenic fungi and oomycete spores, and their preventive value has been demonstrated through indoor pot inoculation experiments.

[0091] Terminology Definitions and Explanations

[0092] In partially substituents Or, the "*" indicates a connection point.

[0093] "More than" means three or more, such as 3, 4, 5 or 6.

[0094] In this document, the term "halogen" refers to fluorine, chlorine, bromine, and / or iodine. Correspondingly, the term "halogenated" refers to fluorination, chlorination, bromination, and / or iodination. Within the scope of this document, when an atom, residue, group, or part is halogenated, the atom at the halogenated position can be monosubstituted, disubstituted, or polysubstituted up to fully substituted by the halogen atom, for example, "halogenated C..." 1-12 Alkyl and Halogenated C 1-12 Alkoxy groups, etc.

[0095] Term "C" 1-12 "alkyl" should be understood to refer to a straight-chain or branched saturated monovalent hydrocarbon group having 1 to 12 carbon atoms, preferably C12. 1-10 Alkyl or C 1-6 Alkyl group. "C" 1-6"alkyl" should be understood to preferably represent a straight-chain or branched saturated monovalent hydrocarbon group having 1, 2, 3, 4, 5, or 6 carbon atoms. The alkyl group is, for example, methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, isobutyl, sec-butyl, tert-butyl, isopentyl, 2-methylbutyl, 1-methylbutyl, 1-ethylpropyl, 1,2-dimethylpropyl, neopentyl, 1,1-dimethylpropyl, 4-methylpentyl, 3-methylpentyl, 2-methylpentyl, 1-methylpentyl, 2-ethylbutyl, 1-ethylbutyl, 3,3-dimethylbutyl, 2,2-dimethylbutyl, 1,1-dimethylbutyl, 2,3-dimethylbutyl, 1,3-dimethylbutyl, or 1,2-dimethylbutyl, or their isomers. In particular, the group has 1, 2, or 3 carbon atoms ("C..."). 1-3 Alkyl), such as methyl, ethyl, n-propyl or isopropyl.

[0096] Term "C" 3-12 "Cycloalkyl" should be understood as representing a saturated monovalent monocyclic, bicyclic, or polycyclic hydrocarbon ring (also called a fused ring hydrocarbon ring) with 3-12 carbon atoms. Bicyclic or polycyclic cycloalkyl includes fused cycloalkyl, bridged cycloalkyl, and spirocyclic cycloalkyl; fused ring refers to a fused ring structure formed by two or more cyclic structures sharing two adjacent ring atoms (i.e., sharing a bond). Bridged ring refers to a fused ring structure formed by two or more cyclic structures sharing two non-adjacent ring atoms. Spirocyclic refers to a fused ring structure formed by two or more cyclic structures sharing a single ring atom. For example, the C 3-12 Cycloalkyl groups can be C 3-8 Monocyclic cycloalkyl groups, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, or C 7-12 And cycloalkyl groups, such as decahydronaphthalene rings.

[0097] The term "3-12 membered heterocyclic group" refers to a saturated or partially saturated monovalent monocyclic or bicyclic hydrocarbon ring containing 1-5, preferably 1-3, heteroatoms selected from N, O, and S. The heterocyclic group can be connected to the rest of the molecule via any one of the carbon atoms or a nitrogen atom (if present). Specifically, the heterocyclic group can include, but is not limited to: 4-membered rings, such as azirmonobutyl or oxobutyl; 5-membered rings, such as tetrahydrofuranyl, dioxacyclopentenyl, pyrrolyl, imidazoyl, pyrazolyl, or pyrrololinyl; or 6-membered rings, such as tetrahydropyranyl, piperidinyl, morpholinyl, dithiaalkyl, thiomorpholinyl, piperazinyl, or trithiaalkyl; or 7-membered rings, such as diazacycloheptyl. Optionally, the heterocyclic group can be benzofused. The heterocyclic group may be bicyclic, such as, but not limited to, a 5,5-membered ring, like a hexahydrocyclopentano[c]pyrrolo-2(1H)-yl ring, or a 5,6-membered bicyclic ring, like a hexahydropyrrolo[1,2-a]pyrazin-2(1H)-yl ring. The nitrogen-containing ring may be partially unsaturated, i.e., it may contain one or more double bonds, such as, but not limited to, 2,5-dihydro-1H-pyrroloyl, 4H-[1,3,4]thiadiazinyl, 4,5-dihydrooxazolyl, or 4H-[1,4]thiazinyl, or it may be benzofused, such as, but not limited to, dihydroisoquinolinyl.

[0098] Term "C" 6-12 "Aryl" should preferably be understood to represent a monovalent aromatic or partially aromatic monocyclic, bicyclic, or tricyclic hydrocarbon ring ("C") having 6, 7, 8, 9, 10, 11, or 12 carbon atoms. 6-12 Aryl), particularly a ring with 6 carbon atoms (“C6 aryl”), such as phenyl; or biphenyl, or a ring with 9 carbon atoms (“C9 aryl”), such as indenyl or indenyl, or a ring with 10 carbon atoms (“C9 aryl”). 10 Aryl), such as tetrahydronaphthyl, dihydronaphthyl or naphthyl.

[0099] The term "5-12-membered heteroaryl" should be understood to include monovalent monocyclic, bicyclic, or tricyclic aromatic ring systems having 5, 6, 7, 8, 9, 10, 11, or 12 ring atoms, particularly 5, 6, 9, or 10 carbon atoms, and containing 1 to 5, preferably 1 to 3, heteroatoms independently selected from N, O, and S. Furthermore, in each case, it may be benzofused. Specifically, the heteroaryl group is selected from thienyl, furanyl, pyrroleyl, oxazolyl, thiazolyl, imidazoleyl, pyrazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl, thiadiazolyl, thia-4H-pyrazolyl, and their benzo[derivatives], such as benzofuranyl, benzothienyl, benzooxazolyl, benzoisooxazolyl, benzoimidazolyl, benzotriazolyl, indazole, indolyl, isindolyl, etc.; or pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl, and their benzo[derivatives], such as quinolinyl, quinazolinyl, isoquinolinyl, etc.; or acrylinyl, inazinyl, purinyl, and their benzo[derivatives]; or terpenolyl, phthalazinyl, quinazolinyl, quinoxolinyl, naphridinyl, pteridinyl, carbazolyl, acridineyl, phenazinyl, phenothiazinyl, phenothiazinyl, etc.

[0100] Unless otherwise stated, heterocyclic, heteroaryl, or heteroaryl groups include all their possible isomers, such as their positional isomers. Thus, for some illustrative, non-limiting examples, pyridyl or pyridylene includes pyridin-2-yl, pyridin-2-yl, pyridin-3-yl, pyridin-3-yl, pyridin-4-yl, and pyridin-4-yl; thiophenyl or thiophene includes thiophene-2-yl, thiophene-2-yl, thiophene-3-yl, and thiophene-3-yl.

[0101] The above refers to the term "C" 1-12 The definition of "alkyl" also applies to compounds containing "C". 1-12 Other terms for "alkyl", such as the term "halogenated C", 1-12 Alkyl or C 1-12 "alkoxy" or "halogenated C" 1-12 "Alkyloxy" etc. Detailed Implementation

[0102] The technical solution of the present invention will be further described in detail below with reference to specific embodiments. It should be understood that the following embodiments are merely illustrative and explanatory of the present invention, and should not be construed as limiting the scope of protection of the present invention. All technologies implemented based on the above content of the present invention are covered within the scope of protection intended by the present invention.

[0103] Unless otherwise stated, the raw materials and reagents used in the following examples are commercially available products or can be prepared by known methods.

[0104] In the following text, those skilled in the art can synthesize the compound represented by formula AC of the present invention by referring to the general synthetic route described above, based on the preparation examples.

[0105] Example 1: Synthesis of Compound A-008

[0106] first step:

[0107]

[0108] 76.4 g of cesium carbonate was placed in a 500 mL round-bottom flask, and 300.0 mL of acetone was added. 40.0 g of A08-1 was added with stirring in an ice bath. After the bubbles stopped rising, 26.9 g of bromoacetaldehyde diethanol condensate was added dropwise, and the reaction was carried out at 60 °C. The reaction was monitored by TLC until complete. The mixture was extracted with water and ethyl acetate, washed with saturated brine, and the organic layers were combined. After concentration, the mixture was separated by column chromatography to obtain compound A08-2, which was a colorless oily liquid, weighing 60.4 g.

[0109] Step Two:

[0110]

[0111] Add 90.0 g of polyphosphoric acid and 200.0 mL of chlorobenzene to a 500 mL round-bottom flask, and stir until the polyphosphoric acid dissolves. Then add 30.0 g of compound A08-2 dissolved in 100.0 mL of chlorobenzene to the reaction flask and react at reflux temperature. After the reaction is complete as detected by TLC, extract with water and ethyl acetate, wash with saturated brine, combine the organic layers, concentrate, and separate by column chromatography to obtain compound A08-3 as 6.3 g of white solid.

[0112] Step 3:

[0113]

[0114] 5.0 g of compound A08-3 was placed in a 250 mL Shrek flask, and 40.0 mL of ultra-dry tetrahydrofuran was added. The mixture was cooled to -78 °C, and 20.0 mL of n-butyllithium solution was added dropwise over 20 min. The mixture was stirred at -78 °C for 1 h, followed by the addition of 8.5 mL of triisopropyl borate over 30 min. The mixture was stirred at -78 °C for 1 h and then brought to room temperature. The reaction was monitored by TLC until complete. The pH was adjusted to acidic with 1 M hydrochloric acid, and the mixture was filtered. The filter cake was washed with n-hexane and dried to obtain 3.5 g of compound A08-4 as a white solid.

[0115] Step 4:

[0116]

[0117] 100.0 mg of compound A08-4 was placed in a 5 mL round-bottom flask, and 1.0 mL of toluene was added. 84.0 mg of methyliminodiacetic acid was added with stirring, and the reaction was carried out at reflux. After the reaction was complete as detected by TLC, the mixture was diluted with water, filtered, the filter cake was washed with diethyl ether, and dried to obtain A-008, a white solid of 148.0 mg.

[0118] Referring to the preparation method in Preparation Example 1 and General Synthetic Route I, the compounds numbered starting with A in Table 1 can be obtained by substituting the raw materials.

[0119] Compound A of the present invention

[0120]

[0121] Table 1

[0122]

[0123]

[0124]

[0125] Example 2: Synthesis of Compound B-019

[0126] first step:

[0127]

[0128] 103.0 g of cesium carbonate was placed in a 500 mL round-bottom flask, and 300.0 mL of acetone was added. 50.0 g of B19-1 was then added with stirring. After the bubbles stopped rising, 33.0 g of bromoacetaldehyde diethanol condensate was added dropwise, and the reaction was carried out at 60 °C. The reaction was monitored by TLC until complete. The mixture was extracted with water and ethyl acetate, washed with saturated brine, and the organic layers were combined. After concentration, the mixture was separated by column chromatography to obtain compound B19-2, which was a colorless oily liquid, weighing 74.0 g.

[0129] Step Two:

[0130]

[0131] 90.0 g of polyphosphoric acid and 200.0 mL of chlorobenzene were added to a 500 mL round-bottom flask and stirred until the polyphosphoric acid dissolved. Then, 30.0 g of compound B19-2 dissolved in 100.0 mL of chlorobenzene was added to the reaction flask, and the reaction was carried out at reflux temperature. After the reaction was completed, water and ethyl acetate were added for extraction, followed by washing with saturated brine. The organic layers were combined, concentrated, and separated by column chromatography to obtain 6.3 g of compound B19-3 as a white solid.

[0132] Step 3:

[0133]

[0134] 40.0 g of cesium carbonate was placed in a 250 mL round-bottom flask, followed by the addition of 1.2 g of cuprous iodide and 120 mL of N,N-dimethylformamide for dissolution. Then, 13.0 g of compound B19-3 and 3,4-dichlorophenol were added with stirring, and the reaction was carried out at 140 °C. After the reaction was complete as detected by TLC, the mixture was diluted with water, extracted with dichloromethane, washed with saturated brine, and the organic layers were combined. The concentrated organic layers were then separated by column chromatography to obtain compound B19-4 as a white solid (13.5 g).

[0135] Step 4:

[0136]

[0137] 5.0 g of compound B19-4 was placed in a 250 mL Shrek flask, and 50.0 mL of tetrahydrofuran was added. The mixture was cooled to -78 °C, and 5.5 mL of n-butyllithium solution was added dropwise over 20 min. The mixture was stirred at -78 °C for 1 h, and then 4.7 mL of triisopropyl borate was added dropwise over 30 min. The mixture was stirred at -78 °C for 1 h, and then brought to room temperature. The reaction was monitored by TLC until complete. The pH was adjusted to acidic with 1 M hydrochloric acid, filtered, and the filter cake was washed with n-hexane and dried to obtain 3.6 g of compound B19-5 as a white solid.

[0138] Step 5:

[0139]

[0140] 100.0 mg of compound B19-5 was placed in a 5 mL round-bottom flask, and 1.0 mL of toluene was added. 76.0 mg of methyliminodiacetic acid was then added with stirring, and the reaction was carried out at reflux. After the reaction was complete as detected by TLC, the mixture was diluted with water, filtered, the filter cake was washed with diethyl ether, and dried to obtain 140.0 mg of B-019 as a white solid.

[0141] Referring to the method of Preparation Example 2 and General Synthetic Route II, the compounds numbered starting with B in Table 2 below can be obtained by substituting the starting materials.

[0142] Compound B of the present invention

[0143]

[0144] Table 2

[0145]

[0146]

[0147]

[0148]

[0149] Example 3 Synthesis of compound C-005

[0150] first step:

[0151]

[0152] 76.4 g of cesium carbonate was placed in a 500 mL round-bottom flask, and 300.0 mL of acetone was added. While stirring, 40.0 g of compound C05-1 was added. After the bubbles stopped rising, 26.9 g of bromoacetaldehyde diethanol condensate was added dropwise, and the reaction was carried out at 60°C. The reaction was monitored by TLC until complete. The mixture was extracted with water and ethyl acetate, washed with saturated brine, and the organic layers were combined. After concentration, the mixture was separated by column chromatography to obtain compound C05-2, which was a colorless oily liquid, weighing 60.0 g.

[0153] Step Two:

[0154]

[0155] 90 g of polyphosphoric acid was added to a 500 mL round-bottom flask, followed by 200.0 mL of toluene. The mixture was stirred until the polyphosphoric acid dissolved. Then, 30.0 g of compound C05-2 dissolved in 100.0 mL of chlorobenzene was added to the round-bottom flask, and the reaction was carried out at reflux. After the reaction was completed, water and ethyl acetate were added for extraction, followed by washing with saturated brine. The organic layers were combined, concentrated, and separated by column chromatography to obtain compound C05-3 as a white solid, 6.3 g.

[0156] Step 3:

[0157]

[0158] 5.0 g of compound C05-3 was placed in a 100 mL round-bottom flask, and 50.0 mL of chloroform was added. After cooling to 0 °C, 4.8 mL of titanium tetrachloride was added dropwise. The mixture was stirred at 0 °C for 10 min, and then 7.4 mL of 1,1-dichloromonomethyl ether was added dropwise. The mixture was then allowed to rise to room temperature. The reaction was detected by TLC and the pH was adjusted to alkaline with saturated sodium bicarbonate solution. The mixture was extracted with dichloromethane, washed with saturated brine, and the organic layers were combined. After concentration, the mixture was separated by column chromatography to obtain compound C05-4 as a white solid, weighing 3.1 g.

[0159] Step 4:

[0160]

[0161] 3.0 g of compound C05-4 was placed in a 100 mL flask, and 30.0 mL of methanol was added. 60 mg of ammonium chloride was then added with stirring, and the reaction was carried out at reflux temperature. After the reaction was complete as detected by TLC, water and dichloromethane were added for extraction, followed by washing with saturated brine. The organic layers were combined, concentrated, and separated by column chromatography to obtain compound C05-5, a yellow liquid, in 2.3 g.

[0162] Step 5:

[0163]

[0164] 1.0 g of compound C05-5 was placed in a 100 mL Shrek flask, and 10.0 mL of ultra-dry tetrahydrofuran was added. The mixture was cooled to -78 °C, and 7.4 mL of n-butyllithium solution was added dropwise over 20 min. The mixture was stirred at -78 °C for 1 h, followed by the addition of 0.8 mL of triisopropyl borate over 30 min. The mixture was stirred at -78 °C for 1 h and then brought to room temperature. The reaction was monitored by TLC until complete. The pH was adjusted to acidic with 1 M hydrochloric acid, and the mixture was filtered. The filter cake was washed with n-hexane and dried to obtain compound C05-6, which was a brown solid weighing 820.0 mg.

[0165] Step 6:

[0166]

[0167] 820.0 mg of compound C05-6 was placed in a 25 mL round-bottom flask, and 8.0 mL of diethyl ether was added, followed by pinacol. The reaction was carried out at room temperature. After the reaction was completed by TLC, water and ethyl acetate were added for extraction, followed by washing with saturated brine. The organic layers were combined, concentrated, and separated by column chromatography to obtain compound C05-7 as a white solid, 930.0 mg.

[0168]

[0169] 100.0 mg of compound C05-7 was placed in a 10 mL round-bottom flask, and 1.0 mL of ethanol was added, followed by phenylhydrazine. The reaction was carried out at room temperature. After the reaction was completed by TLC, water and dichloromethane were added for extraction, followed by washing with saturated brine. The organic layers were combined, concentrated, and separated by column chromatography to obtain compound C-005 as a white solid (80.0 mg). Following the general synthetic route III of Example 3, by substituting the starting materials, the compounds numbered starting with C in Table 3 below can be obtained.

[0170] Compound of formula C of the present invention

[0171]

[0172] Table 3

[0173]

[0174] Note: In Table 1-3, when R1 and R2 are selected from... When the groups are equal, N in the above groups coordinates with B.

[0175] Table 4. Compound structure characterization data

[0176] Table 4 shows the mass spectrometry data and / or data for the compounds listed in Tables 1-3. 1 H-NMR data. Unless otherwise specified, deuterated chloroform (CDCl3), deuterated methanol (CD3OD-d4), deuterated dimethyl sulfoxide (DMSO-d6), or heavy water (D2O) are used as test solvents.

[0177] In Table 4 and throughout the following descriptions, "NMR" refers to nuclear magnetic resonance spectroscopy, and "MS" represents mass spectrometry. The following abbreviations will also be used:

[0178] s = single peak, br = broad peak, d = double peak, dd = double double peak, t = triple peak, td = triple double peak, q = quartet, m = multiple peak.

[0179] Table 4

[0180]

[0181]

[0182]

[0183]

[0184]

[0185] Note: "-" in Table 4 indicates that NMR data for this compound was not tested.

[0186] Biological Examples

[0187] Given that *Pyrrosia lingua* infects plants via appressorium-mediated infection and can be cultured artificially indoors, *Pyrrosia lingua* can be used as a model pathogen to test the inhibitory effects of the compounds of this invention on conidium germination and appressorium formation. The relevant activities of the compounds of this invention are illustrated by the following examples.

[0188] Biological Example G1: Inhibitory effect of borate esters on conidial germination and appressorium formation of *Pyrrosia lingua*

[0189] 1. Experimental material: P131 strain of *Pyrrosia lingua*.

[0190] 2. Experimental Method: The *Pyrrosia lingua* strain P131 was inoculated onto tomato-oat agar plates (OTA) and incubated at 28°C. After 3-5 days, the *Pyrrosia lingua* colonies on the OTA were completely broken up and then evenly spread onto new OTA plates and incubated at 28°C. When new mycelia emerged (generally 1-2 days), the mycelia were broken up with cotton swabs, rinsed with sterile water, and dried. The petri dishes were covered with a single layer of gauze and incubated at 28°C for 48 hours, resulting in the production of a large number of conidia on the OTA surface. The culture on the OTA was washed off with sterile water, filtered through three layers of lens paper, and the filtrate was the conidia solution. The conidia concentration was adjusted to 2 × 10⁻⁶. 5 Add the sample solution of the target compound to the sample solution at a concentration of 6.25 ppm and 1.56 ppm to prepare working solutions. Spot the solutions sequentially onto hydrophobic glass slides. Nine spots are spotted on each slide, and the slides are then treated in the dark and kept moist. Observe and count the samples under a microscope after 12 hours.

[0191] 3. Statistical Analysis: Three inoculation sites were counted on each hydrophobic slide. At each inoculation site, the number of germinating conidia and appressorium formations from 100 conidia at its center were counted. The average of the three sets of data was calculated to obtain the conidia germination rate and appressorium formation rate. Parallel experiments using solvent were used as controls to calculate the inhibitory effect of the test compound on conidia germination and appressorium formation. Table 5 shows the data for biological example G1 of the compound of this invention, where "-" indicates no inhibitory effect at a concentration of 6.25 ppm, "+" indicates an inhibition rate of less than or equal to 50% at a concentration of 6.25 ppm, "++" indicates an inhibition rate of more than 50% at a concentration of 6.25 ppm, and "+++" indicates an inhibition rate of more than 50% at a concentration of 1.56 ppm.

[0192] Table 5

[0193]

[0194]

[0195] Biological Example G2: Control Effect of Borate Compounds on Potted Rice Infected by Pyrethrum orientalis

[0196] 1. Experimental materials: Pyridae oryzae strain 16-117, rice varieties CO39 and Xiangwanxian 11.

[0197] 2. Experimental Methods: Sporulation and spore preparation were the same as in Biological Example G1. The conidial concentration was adjusted to 5 × 10⁻⁶. 4Add the test compound stock solution to the solution at a concentration of 100 ppm to prepare a 100 ppm working solution. Spray 15 mL of the working solution onto susceptible rice varieties Xiangwanxian 11 and CO39, spraying 10 seedlings of each treatment that are 2-3 weeks old. Incubate in the dark under moist conditions for 48 h, then proceed with normal culture. Evaluate the control efficacy of the test compound against rice blast 7 days after inoculation.

[0198] 3. Statistics and Analysis: Table 6 shows the data of biological example G2 of the compounds of the present invention (average values ​​of each treatment). Rice blast leaf blast disease surveys were conducted in accordance with the agricultural industry standard "Technical Regulations for Field Monitoring of Rice Blast Resistance" (NY / T3685-2020). Specific standards are as follows: Grade 0: No disease on the entire leaf; Grade 1: Small brown necrotic spots on the leaf; Grade 2: Larger brown necrotic spots (1mm-2mm in diameter) on the leaf, but no typical lesions; Grade 3: Typical rice blast lesions, lesion area <2%; Grade 4: Typical rice blast lesions, 2% ≤ lesion area <5%; Grade 5: Typical rice blast lesions, 5% ≤ lesion area <10%; Grade 6: Typical rice blast lesions, 10% ≤ lesion area <25%; Grade 7: Typical rice blast lesions, 25% ≤ lesion area <50%; Grade 8: Typical rice blast lesions, 50% ≤ lesion area <75%; Grade 9: Typical rice blast lesions, lesion area ≥75%.

[0199] Table 6

[0200]

[0201]

[0202] Biological Example G3: The Control Effect of Borate Compounds on Anthracnose Infection of Exvial Mango Leaves

[0203] 1. Experimental materials: Mango anthracnose strain SC2-1 and newly green 'Guifei' mango tender leaves were placed in an inoculation box for later use.

[0204] 2. Experimental Method: The anthrax strain SC2-1 was inoculated onto tomato-oat agar plates (OTA) and incubated at 25℃ under constant temperature and light. After 5-7 days, the mycelia on the OTA were gently broken with a cotton swab, rinsed with sterile water, and air-dried. The petri dish was covered with a single layer of gauze and incubated at 25℃ under light for 3-5 days, resulting in the production of a large number of spores on the OTA surface. The culture on the OTA was washed off with sterile water, filtered through three layers of lens paper, and the filtrate was the spore solution. The spore concentration was adjusted to 1×10⁻⁶. 6 Add the test compound stock solution to the solution at a concentration of 10 μL / mL to prepare a 100 ppm working solution. Spot 10 μL of the working solution onto the surface of mango leaves, treat in the dark for 24 h, and then culture normally. Evaluate the control effect of the test compound 7 days after inoculation.

[0205] 3. Statistics and Analysis: Five leaves were counted for each treatment, and one inoculation point was counted for each leaf. The lesion area at each inoculation point was counted, and the average value was calculated to obtain the lesion area. The lesion area obtained from parallel experiments using the solvent was used as a control to calculate the inhibitory effect of the test compound on mango leaves infected with anthracnose. Table 7 shows the data for biological example G3 of the compound of the present invention. "+" indicates an inhibition effect of less than 40% at 200 ppm, "++" indicates an inhibition effect of more than 40% at 100 ppm, and "+++" indicates an inhibition effect of more than 80% at 50 ppm.

[0206] Table 7

[0207]

[0208]

[0209] Biological Example G4: Control Effect of Borate Compounds on Fusarium Head Blight Infection in Potted Wheat

[0210] 1. Experimental materials: Fusarium graminearum strain Fg0609 and "Fielder" wheat cultured to the pre-ear and grain flowering stage.

[0211] 2. Experimental Method: Fusarium graminearum mycelium cakes grown on PDA medium for 5 days were placed in CMC liquid medium and incubated at 28℃ and 180 rpm for 7 days. The mixture was filtered through three layers of lens paper, and the filtrate was used as the spore solution. The spore solution concentration was adjusted to 1×10⁻⁶. 5 Add the stock solution of the test compound to the solution at a concentration of 10 μL / mL to prepare a 100 ppm working solution. Use a pipette to inject 10 μL of the working solution into wheat ears before flowering, five ears per treatment. After 2 days of moist incubation, the wheat is cultured normally. The control efficacy of the test compound is evaluated 14 days after inoculation.

[0212] 3. Statistics and Analysis: Table 8 shows the data of biological example G4 of the compound of the present invention (average value of each treatment). The wheat scab disease survey was conducted in accordance with the agricultural industry standard "Technical Regulations for Identification of Resistance to Fusarium Head Blight in Regional Wheat Trials" (NY / T2954-2016), with the following specific standards: Grade 0: No visible symptoms on inoculated spikelets; Grade 1: Disease only on inoculated spikelets; or disease on individual adjacent spikelets, but the lesions do not extend to the rachis; Grade 2: Disease on the rachis, with diseased spikelets accounting for less than 1 / 4 of the total spikelets; Grade 3: Disease on the rachis, with diseased spikelets accounting for 1 / 4-1 / 2 of the total spikelets; Grade 4: Disease on the rachis, with diseased spikelets accounting for more than 1 / 2 of the total spikelets.

[0213] Table 8

[0214]

[0215] Biological Example G5: Control Effect of Borate Compounds on Wheat Powdery Mildew Infection of Isolated Leaf Segments

[0216] 1. Experimental materials: Wheat powdery mildew strain 19-11-1-2 and “Fielder” wheat were cultured normally for 2-3 weeks, and 4cm leaf segments were cut and placed in inoculation trays for later use.

[0217] 2. Experimental Method: Spores were scraped from the leaves of diseased potted plants and placed in small vials for later use. The stock solution of the test compound was diluted to a working concentration of 100 ppm, and the leaf segments of each group were soaked for 1 hour. The leaf segments of each group were placed on water agar medium, and the spores were evenly distributed onto the surface of the leaf segments using a blower. Ten leaf segments were treated in each group, and the results were counted after 5-7 days.

[0218] 3. Statistics and Analysis: Table 10 shows the data of biological example G6 of the compounds of the present invention (average values ​​of each treatment). The wheat powdery mildew disease survey was conducted in accordance with the agricultural industry standard "Guidelines for Indoor Bioassay Tests of Pesticides - Fungicides Part 4: Pot Test Method for Control of Wheat Powdery Mildew" (NY / T1156.4-2006), with the following specific standards: Grade 0: No disease; Grade 1: Lesion area less than 5% of leaf area; Grade 3: Lesion area 6%-15% of leaf area; Grade 5: Lesion area 16%-25% of leaf area; Grade 7: Lesion area 26%-50% of leaf area; Grade 9: Lesion area more than 51% of leaf area.

[0219] Table 9

[0220]

[0221]

[0222] Biological Example G6: Control Effect of Borate Compounds on Phytophthora infestation of Potted Potatoes

[0223] 1. Experimental materials: The seedlings of the pathogenic Phytophthora blight medium-strong strain "MZ" and the potato late blight susceptible variety "Desiree" were cultured normally for 2 weeks and then placed in an inoculation box for use.

[0224] 2. Experimental Method: The sporangia were cultured on PDA medium. After sporangia were produced, they were washed off with sterile water, filtered through double-layered gauze to prepare a sporangia suspension, and incubated at 4℃ in the dark for 3 hours. The prepared sporangia solution was then adjusted with sterile water at 4℃ to a concentration of 4×10⁻⁶. 3A suspension of sporangia / mL was prepared. The stock solution of the test compound was diluted with water to a working concentration of 100 ppm. Before inoculation, the plants to be treated were placed in an artificial climate greenhouse at 20℃ for acclimatization 4 hours in advance. After acclimatization, the working solution was sprayed evenly on both sides of the leaves of the treated plants. Five plants were treated per treatment, and each plant was sprayed with 60 mL. After the working solution was allowed to air dry naturally, the plants were cultured normally for 24 hours. Then, the plants were sprayed with the prepared sporangium suspension for inoculation. After 24 hours of dark treatment, the plants were cultured under normal light (20℃, 18 hours light / 6 hours dark). The disease situation was observed at any time. The control effect of the test compound on potato late blight was evaluated after 7 days.

[0225] 3. Statistics and Analysis: Table 11 shows the data of biological example G7 of the compound of the present invention (average of each treatment). Potato late blight disease investigation was conducted according to the agricultural industry standard "Technical Specification for Indoor Identification of Potato Late Blight Resistance" (NY / T3063-2016), with the following specific standards: Grade 0: No symptoms on inoculated leaves; Grade 1: Only pinhead-sized necrotic spots appear on the leaves; Grade 2: Lesion diameter less than 0.5 cm, without a surrounding chlorotic halo; Grade 3: Lesion diameter 0.5 cm-1 cm, water-soaked lesions with a surrounding chlorotic halo, white mycelium visible on the lesion surface; Grade 4: Lesions continue to expand, occupying 1 / 2 of the total leaf area, with a distinct chlorotic halo around the lesion and a distinct white mold layer; Grade 5: Lesions occupy more than 2 / 3 of the leaf area, with a large amount of white mold on the lesion surface and tissue necrosis.

[0226] Table 10

[0227]

[0228]

[0229] Biological Example G7: Control Effect of Borate Compounds on Potted Peppers Infected with Phytophthora capsici

[0230] 1. Experimental materials: The *Phytophthora capsici* strain BYA5 and *Horn Pepper* seedlings were cultured normally for 2 weeks and then placed in an inoculation box for later use.

[0231] 2. Experimental Methods: The strain was cultured on PDA medium for 10 days, then soaked in a small amount of sterile water and placed at 4°C in the dark for 3 hours before storage. The prepared sporangia solution was adjusted with sterile water at 4°C to a concentration of 1×10⁻⁶. 5A suspension of spores / mL was prepared. The stock solution of the test compound was diluted with water to a working concentration of 100 ppm. Five plants were treated per treatment, and each plant was sprayed with 20 mL of the working solution of the compound. After air drying, the plants were inoculated by drenching the roots with 10 mL of the prepared spore suspension. After 24 hours of dark treatment, the plants were cultured under normal light (20℃, 18 hours light / 6 hours dark), and the disease development was observed at any time. The control effect of the test compound on pepper blight was evaluated after 5-7 days.

[0232] 3. Statistics and Analysis: Table 12 shows the data of biological example G8 of the compounds of the present invention (average values ​​of each treatment). The investigation of pepper blight disease was conducted in accordance with the agricultural industry standard "Technical Specification for Identification of Pepper Disease Resistance Part 1: Technical Specification for Identification of Pepper Disease Resistance" (NY / T2060.1-2011). The specific standards are as follows: Grade 0: No symptoms; Grade 1: Slight blackening of the seedling root and stem, leaves do not wilt or wilt recoverably; Grade 2: Blackening of the seedling root and stem up to 1-2 cm, irreversible wilting of leaves, occasional shedding of lower leaves; Grade 3: Blackening of the seedling root and stem exceeding 2 cm, obvious wilting of leaves or obvious leaf drop; Grade 4: Blackening and constriction of the seedling root and stem, all leaves except the growing point fall off or the plant wilts; Grade 5: Plant dies.

[0233] Table 11

[0234]

[0235]

[0236] The embodiments of the present invention have been described above. However, the present invention is not limited to the above embodiments. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. The stereoisomers, racemates, pharmaceutically acceptable salts, or solvates of the compound represented by Formula I: in, R1 and R2, together with their two attached O atoms and B, constitute an unsubstituted or optionally substituted group consisting of one, two or more Ra groups: a 5-12 membered heterocyclic group or a benzo5-12 membered heterocyclic group; wherein Ra is selected from =O, C 1-12 Alkyl or halogenated C 1-12 alkyl; R3 is selected from H or R 33 R 33 Selected from -C=NX-Rb; X is selected from NH or O; Rb is selected from C 1-12 Alkyl, Halogenated C 1-12 Alkyl, C 6-12 Aryl, 5-12 heteroaryl, -C 1-12 Alkyl-C 6-12 Aryl, -C 1-12 Alkyl-5-12-membered heteroaryl, -CO-C 1-12 Alkyl, -CO-C 6-12 Aryl, -CO-5-12 heteroaryl, -S(O)2-C 6-12 Aryl-C 1-12 Alkyl or -S(O)2-5-12-membered heteroaryl-C 1-12 alkyl; R4 and R5 may be the same or different, and are independently selected from H, CN, halogens, and C. 1-12 Alkyl, Halogenated C 1-12 Alkyl, C 1-12 Alkoxy, halogenated C 1-12 Alkoxy, -OC 6-12 Aryl or -O-5-12 heteroaryl; the -OC 6-12 C in aryl and -O-5-12-membered heteroaryl 6-12 The aryl group and the 5-12 heteroaryl group are independently unsubstituted, or optionally substituted by one, two or more Rc groups; said Rc group is selected from CN, halogen, C. 1-12 Alkyl, C 1-12 Alkyl groups, -COOC 1-12 Alkyl, -N(C) 1-12 alkyl)2 or -NHC 1-12 alkyl.

2. The compound according to claim 1, its stereoisomer, racemate, pharmaceutically acceptable salt or solvate, characterized in that, R1 and R2 together with their two attached O atoms constitute unsubstituted or optionally substituted groups with one, two or more Ra groups: 5-8 membered heterocyclic groups or benzo5-6 membered heterocyclic groups; wherein Ra is selected from =O, C 1-6 Alkyl or halogenated C 1-6 alkyl; Preferably, R1 and R2, together with their two attached O atoms and B, constitute an unsubstituted or optionally substituted group consisting of one, two or more Ra groups: a 5-8 membered heterocyclic group or a benzo5-8 membered heterocyclic group; wherein Ra is selected from =O, C 1-6 Alkyl or halogenated C 1-6 Alkyl group; the 5-8 membered heterocyclic group contains B and O, and further contains one or both of N or O; when N is present, Ra is substituted on N or on a carbon atom; Preferably, The following groups are indicated to be unsubstituted or optionally substituted by one, two or more Ra atoms, together with R1 and R2 and the two O atoms attached to them and B: Ra is selected from =O, methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, or trifluoromethyl.

3. The compound according to claim 1 or 2, wherein its stereoisomer, racemate, pharmaceutically acceptable salt, or solvate is characterized in that, R3 is selected from H or R 33 R 33 Selected from -C=NX-Rb; X is selected from NH or O; Rb is selected from C 1-6 Alkyl, C 6-12 Aryl, 5-12 heteroaryl, -C 1-6 Alkyl-C 6-12 Aryl, -C 1-6 Alkyl-5-12-membered heteroaryl, -CO-C 1-6 Alkyl, -CO-C 6-12 Aryl, -CO-5-12 heteroaryl, -S(O)2-C 6-12 Aryl-C 1-6 Alkyl or -S(O)2-5-12-membered heteroaryl-C 1-6 alkyl; R4 and R5 may be the same or different, and are independently selected from H, CN, halogens, and C. 1-6 Alkyl, C 1-6 Alkoxy, -OC 6-12 Aryl or -O-5-12 heteroaryl; the -OC 6-12 C in aryl and -O-5-12-membered heteroaryl 6-12 The aryl group and the 5-12 heteroaryl group are independently unsubstituted, or optionally substituted by one, two or more Rc groups; said Rc group is selected from CN, halogen, C. 1-6 Alkyl, C 1-6 Alkyl groups, -COOC 1-6 Alkyl, -N(C) 1-6 alkyl)2 or -NHC 1-6 alkyl.

4. The compound according to any one of claims 1-3, wherein its stereoisomer, racemate, pharmaceutically acceptable salt, or solvate is characterized in that, The compound represented by Formula I is selected from the structure represented by Formula A, or Formula B, or Formula C: Among them, R1, R2 and R 33 It has the definition as described in any one of claims 1-3; In formula A, R 31 and R 41 They may be the same or different, and are independently selected from H, CN, halogens, and C. 1-6 Alkyl or C 1-6 Alkyl groups; and R 31 and R 41 Not both H; In formula B, R 32 Selected from -OC 6-12 Aryl or -O-5-12 heteroaryl; the -OC 6-12 C in aryl and -O-5-12-membered heteroaryl 6-12 The aryl group and the 5-12 heteroaryl group are independently unsubstituted, or optionally substituted by one, two, or three Rc groups; said Rc groups are selected from CN, halogens, C. 1-6 Alkyl, C 1-6 Alkyl groups, -COOC 1-6 Alkyl, -N(C) 1-6 alkyl)2 or -NHC 1-6 alkyl; In formula C, R 42 and R 51 Whether the same or different, they are independently selected from CN, halogen, and C. 1-6 Alkyl or halogenated C 1-6 alkyl.

5. The compound according to claim 4, wherein its stereoisomer, racemate, pharmaceutically acceptable salt or solvate, is characterized in that, In formula A, R1 and R2, together with the two O atoms attached to them and B, form the following groups: Ra may be the same as or different from each other, and are independently selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, or trifluoromethyl; R 31 The 4- or 5-substituent is attached to benzothiophene; R 41 It is a substituent at the 7-position of benzothiophene; R 31 Selected from CN, F, Cl, methyl, ethyl, or methoxy; R 41 Selected from H, F, Cl or methoxy; Preferably, in formula B, R1 and R2, together with the two O atoms attached to them and B, constitute the following groups: Ra may be the same or different, and each can be independently selected from methyl, ethyl, n-propyl, isopropyl, or n-butyl; In formula B, R 32 Selected from -O-phenyl, -O-1,3-benzoxyl, or -O-pyridyl; wherein the phenyl, 1,3-benzoxyl, or pyridyl group is independently unsubstituted, or optionally substituted by one, two, or more Rc groups; wherein the Rc group is selected from CN, F, Cl, C. 1-3 Alkyl, C 1-3 Alkyl groups, -COOC 1-3 Alkyl, -N(C) 1-3 alkyl)2 or -NHC 1-6 alkyl; In formula B, R 32 Substituents at positions 4, 5, 6, or 7; In formula B, when R 32 When selected from -O-1,3-benzoxyl groups, it is In formula B, when R 32 When selected from -O-pyridinyl, it is 2-pyridinoxy; Preferably, in formula C, R1 and R2, together with the two O atoms attached to them and B, constitute the following groups: Ra may be the same or different, and each can be independently selected from methyl, ethyl, n-propyl, isopropyl, n-butyl or tert-butyl; In formula C, R 33 Selected from -C=NX-Rb; X is selected from NH or O; Rb is selected from C 1-6 Alkyl, phenyl, pyridyl, -C 1-6 Alkyl-phenyl, -C 1-6 alkyl-pyridyl, -CO-C 1-6 Alkyl, -CO-phenyl, -CO-pyridyl, -S(O)2-phenyl-C 1-6 Alkyl or -S(O)2-pyridyl-C 1-6 alkyl; In formula C, R 42 and R 51 They may be the same or different, and are independently selected from halogens; In formula C, R 42 and R 51 Substituents at positions 5 and 7, respectively; In formula C, R 42 and R 51 The substituents are at positions 5 and 7, respectively, and are both Cl.

6. The compound according to claim 4 or 5, wherein its stereoisomer, racemate, pharmaceutically acceptable salt, or solvate is characterized in that, Formula A is selected from compounds defined by the following groups, their stereoisomers, racemates, pharmaceutically acceptable salts, or solvates: Preferably, Formula B is selected from compounds defined by the following groups, including their stereoisomers, racemates, pharmaceutically acceptable salts, or solvates: Preferably, Formula C is selected from compounds defined by the following groups, including their stereoisomers, racemates, pharmaceutically acceptable salts, or solvates:

7. The use of the compound of Formula I according to any one of claims 1-6, its isomers, pharmaceutically acceptable salts or solvates as bactericides.

8. The use according to claim 7, characterized in that, The fungicide is used to inhibit the germination of fungal and oomycete spores and the formation of appressoriums, as well as to prevent and control plant diseases caused by fungi and oomycetes.

9. The use according to claim 7 or 8, characterized in that, The fungus is at least one of the following: Pyrrosia lingua, Anthracnose, Fusarium head blight, wheat powdery mildew, and Phytophthora. Preferably, the plant diseases caused by the fungi and oomycetes are selected from the following: rice sheath blight, rice blast, rice false smut, sesame spot, and bakanae disease; wheat scab, powdery mildew, stripe rust, stem rust, leaf rust, root rot, and sheath blight; corn large leaf spot, small leaf spot, anthracnose, stem base rot, rust, sheath blight, Curvularia leaf spot, common smut, and powdery mildew; mango anthracnose, potato late blight, strawberry gray mold, soybean Phytophthora blight, pepper Phytophthora blight, grape downy mildew, and cucumber downy mildew.

10. A bactericide composition, characterized in that, It includes the compound of Formula I as described in any one of claims 1-6, its isomers, pharmaceutically acceptable salts or solvates.

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