Method for controlling insect pests of plants

Abstract

The present invention provides a technology useful in the agronomic horticultural field, such as a technology for controlling plant pests. Pests of plants are controlled by using various glutamic acid derivatives.

Description

Technical Field

[0001] The present invention relates to a technique useful in the field of agronomy and horticulture, such as a technique for controlling plant pests. Background Art

[0002] According to a report by the United Nations, the world population is expected to increase by 2 billion people in the next 30 years, reaching 9.7 billion people by 2050. The Food and Agriculture Organization of the United Nations states that this population increase will require agricultural production (e.g., the production of food, feed, and biofuels) in 2050 to increase by more than 50% compared to 2012 (Non-Patent Document 1).

[0003] On the other hand, damages by insect pests and the like in plants have been reported, for example, 26 to 40% of grains are lost due to insect pests, pathogenic bacteria, weeds, viruses and the like.

[0004] Pest control technology mostly relies on pest control using insecticide-resistant chemical synthetic pesticides, but pesticide-resistant pests have appeared frequently. Therefore, it is necessary to develop pest control technology that does not allow pesticide-resistant pests to appear.

[0005] It is known that when plants are fed by pests, glutamate flowing out of injured cells activates Ca 2+ The glutamate receptor GLR3.3 / 3.6 is a permeable ion channel that produces Ca 2+ The signal is rapidly propagated through the vascular bundle, and even in the distal organs that are not directly ingesting the food, jasmonic acid, a resistance plant hormone, is synthesized within a few minutes, thereby activating a systemic defense mechanism (Non-Patent Document 2).

[0006] Prior art literature

[0007] Non-patent literature

[0008] Non-patent literature 1: FAO, The future of food and agriculture-Trends and challenges, 2017.

[0009] Non-patent document 2: Toyota, M et al., Glutamate triggers long-distance, calcium-based plant defense signaling. Science. 2018 Sep 14; 361(6407): 1112-1115. Summary of the invention

[0010] Technical problem solved by the invention

[0011] The problem to be solved by the present invention is to provide a technology useful in the field of agronomy and horticulture, such as a technology for controlling plant pests.

[0012] Technical means of solving problems

[0013] The present inventors have conducted intensive studies to solve the above problems and have found that various glutamic acid derivatives can induce resistance to plant pests, thereby controlling plant pests, thereby completing the present invention.

[0014] That is, the present invention can be exemplified as follows.

[0015] [1] A composition for inducing insect pest resistance in plants or for controlling insect pests in plants,

[0016] The composition contains the following ingredients (A):

[0017] (A) a compound represented by the general formula (I) below,

[0018] In formula (I),

[0019] n represents an integer from 1 to 3, i.e., 1, 2 or 3,

[0020] X represents an interatomic bond, an oxygen atom (O), a nitrogen atom (NH) bonded to a hydrogen atom, a nitrogen atom (NMe) bonded to a methyl group, a sulfur atom (S) or a 4-phenoxy group,

[0021] R 1 represents a hydrogen atom (H), an amidine group or an acyl group,

[0022] R 2 Represents OR 4 or NHR 4 ,

[0023] R 3 Represents C(=O)-R 5 , sulfonic acid (SO3H), phosphoric acid (PO3H2) or SO2R 6 ,

[0024] R 4 represents a hydrogen atom (H) or an optionally substituted alkyl group having 1 to 8 carbon atoms,

[0025] R 5 represents an optionally substituted alkyl group having 1 to 8 carbon atoms, an amino acid, a dipeptide, OR 7 or NR 8 R 9 ,

[0026] R 6 represents a methyl group or an optionally substituted phenyl group,

[0027] R 7 represents a hydrogen atom (H) or an alkyl group having 1 to 8 carbon atoms,

[0028] R 8 and R 9 Each independently represents a hydrogen atom (H), an optionally substituted alkyl group having 1 to 8 carbon atoms, or an optionally substituted phenyl group.

[0029] [2] According to the composition, wherein

[0030] n is 2.

[0031] [3] According to the composition, wherein

[0032] X is an interatomic bond.

[0033] [4] According to the composition, it satisfies any one of the following conditions:

[0034] (1) n is 2, X is an interatomic bond, R 2 is hydroxyl group, R 3 C(=O)-R 5 ;

[0035] (2) n is 2, X is an interatomic bond, R 1 is a hydrogen atom, R 2 is hydroxyl group, R 3 C(=O)-R 5 , R 5 is a group other than a hydroxyl group;

[0036] (3) n is 2, X is an interatomic bond, R 1 is a group other than a hydrogen atom, R 2 is hydroxyl group, R 3 C(=O)-R 5 , R 5 is hydroxyl group;

[0037] (4) n is 2, X is an interatomic bond, R 1 is a hydrogen atom, R 2 is a group other than a hydroxyl group, R 3 It is C(=O)-OH.

[0038] [5] According to the composition, wherein

[0039] The component (A) is selected from the compounds represented by the following formulae (Compound 1) to (Compound 58) and (Compound 67) to (Compound 75).

[0040] [6] According to the composition, wherein

[0041] The insect pest is an insect pest caused by an organism classified into the order Lepidoptera, Hemiptera, Coleoptera, Diptera, Orthoptera, Thysanoptera, Tyrannosaurus, Collembola, Acarina, or Stylophora.

[0042] [7] According to the composition, wherein

[0043] The insect pests are classified into the families of Plutella xylostella, Noctuidae, Pyralidae, Leafroller, Leafminer, Fruitborer, Gnaphalidae, Grassworm, Lightmoth, Lymantria, Cicadidae, Rice Pseudopsidae, Psyllidae, Aphididae, Aleyrodidae, Coccoidea, Miridae, Net Bugs, Pentatomidae, Longistidae, Scarabidae, Click Beetle, Coccinella, Cerambycidae, Chilophoridae, Curculionidae, Muscidae, Calliphoridae, Pests caused by organisms of the Sarcophagidae, Tachymycetes, Tephritidae, Gramomycetes, Ornithopoidea, Xiphophidae, Stigmidae, Coneheaded Grasshoppers, Thripidae, Thripidae, Thripidae, Acanthidae, Neotylenchidae, Acanthophoridae, Collembola, Tetranychus, Dermatophytidae, Acaridae, Sarcoptidae, Myxomycetes or Slugidae.

[0044] [8] According to the composition, wherein

[0045] The plant is a plant of the Poaceae family, the Solanaceae family, the Cucurbitaceae family, the Leguminosae family, the Cruciferae family, the Rosaceae family, the Moraceae family, the Malvaceae family, the Apiaceae family, the Liliaceae family, the Asteraceae family, the Amaranthaceae family, the Ericaceae family, the Vitaceae family, the Rutaceae family, the Rubiaceae family, the Oleaceae family, the Lauraceae family, the Anacardiaceae family, the Sapindaceae family or the Lamiaceae family.

[0046] [9] A method for inducing insect pest resistance in plants, comprising: applying the following component (A) to the plants:

[0047] (A) a compound represented by the general formula (I) below,

[0048] In formula (I),

[0049] n represents an integer from 1 to 3, i.e., 1, 2 or 3,

[0050] X represents an interatomic bond, an oxygen atom (O), a nitrogen atom (NH) bonded to a hydrogen atom, a nitrogen atom (NMe) bonded to a methyl group, a sulfur atom (S) or a 4-phenoxy group,

[0051] R 1 represents a hydrogen atom (H), an amidine group or an acyl group,

[0052] R 2 Represents OR 4 or NHR 4 ,

[0053] R3 Represents C(=O)-R 5 , sulfonic acid (SO3H), phosphoric acid (PO3H2) or SO2R 6 ,

[0054] R 4 represents a hydrogen atom (H) or an optionally substituted alkyl group having 1 to 8 carbon atoms,

[0055] R 5 represents an optionally substituted alkyl group having 1 to 8 carbon atoms, an amino acid, a dipeptide, OR 7 or NR 8 R 9 ,

[0056] R 6 represents a methyl group or an optionally substituted phenyl group,

[0057] R 7 represents a hydrogen atom (H) or an alkyl group having 1 to 8 carbon atoms,

[0058] R 8 and R 9 Each independently represents a hydrogen atom (H), an optionally substituted alkyl group having 1 to 8 carbon atoms, or an optionally substituted phenyl group.

[0059]

[10] A method for controlling plant pests, comprising: applying the following component (A) to the plant:

[0060] (A) a compound represented by the general formula (I) below,

[0061] In formula (I),

[0062] n represents an integer from 1 to 3, i.e., 1, 2 or 3,

[0063] X represents an interatomic bond, an oxygen atom (O), a nitrogen atom (NH) bonded to a hydrogen atom, a nitrogen atom (NMe) bonded to a methyl group, a sulfur atom (S) or a 4-phenoxy group,

[0064] R 1 represents a hydrogen atom (H), an amidine group or an acyl group,

[0065] R 2 Represents OR 4 or NHR 4 ,

[0066] R 3 Represents C(=O)-R 5 , sulfonic acid (SO3H), phosphoric acid (PO3H2) or SO2R 6 ,

[0067] R4 represents a hydrogen atom (H) or an optionally substituted alkyl group having 1 to 8 carbon atoms,

[0068] R 5 represents an optionally substituted alkyl group having 1 to 8 carbon atoms, an amino acid, a dipeptide, OR 7 or NR 8 R 9 ,

[0069] R 6 represents a methyl group or an optionally substituted phenyl group,

[0070] R 7 represents a hydrogen atom (H) or an alkyl group having 1 to 8 carbon atoms,

[0071] R 8 and R 9 Each independently represents a hydrogen atom (H), an optionally substituted alkyl group having 1 to 8 carbon atoms, or an optionally substituted phenyl group.

[0072]

[11] A method for producing a plant, comprising: applying the following component (A) to a plant to cultivate the plant:

[0073] (A) a compound represented by the general formula (I) below,

[0074] In formula (I),

[0075] n represents an integer from 1 to 3, i.e., 1, 2 or 3,

[0076] X represents an interatomic bond, an oxygen atom (O), a nitrogen atom (NH) bonded to a hydrogen atom, a nitrogen atom (NMe) bonded to a methyl group, a sulfur atom (S) or a 4-phenoxy group,

[0077] R 1 represents a hydrogen atom (H), an amidine group or an acyl group,

[0078] R 2 Represents OR 4 or NHR 4 ,

[0079] R 3 Represents C(=O)-R 5 , sulfonic acid (SO3H), phosphoric acid (PO3H2) or SO2R 6 ,

[0080] R 4 represents a hydrogen atom (H) or an optionally substituted alkyl group having 1 to 8 carbon atoms,

[0081] R 5represents an optionally substituted alkyl group having 1 to 8 carbon atoms, an amino acid, a dipeptide, OR 7 or NR 8 R 9 ,

[0082] R 6 represents a methyl group or an optionally substituted phenyl group,

[0083] R 7 represents a hydrogen atom (H) or an alkyl group having 1 to 8 carbon atoms,

[0084] R 8 and R 9 Each independently represents a hydrogen atom (H), an optionally substituted alkyl group having 1 to 8 carbon atoms, or an optionally substituted phenyl group.

[0085]

[12] According to the method, wherein

[0086] n is 2.

[0087]

[13] According to the method, wherein

[0088] X is an interatomic bond.

[0089]

[14] According to the method, any of the following conditions is met:

[0090] (1) n is 2, X is an interatomic bond, R 2 is hydroxyl group, R 3 C(=O)-R 5 ;

[0091] (2) n is 2, X is an interatomic bond, R 1 is a hydrogen atom, R 2 is hydroxyl group, R 3 C(=O)-R 5 , R 5 is a group other than a hydroxyl group;

[0092] (3) n is 2, X is an interatomic bond, R 1 is a group other than a hydrogen atom, R 2 is hydroxyl group, R 3 C(=O)-R 5 , R 5 is hydroxyl group;

[0093] (4) n is 2, X is an interatomic bond, R 1 is a hydrogen atom, R 2 is a group other than a hydroxyl group, R 3 It is C(=O)-OH.

[0094]

[15] According to the method, wherein

[0095] The component (A) is selected from the compounds represented by the following formulae (Compound 1) to (Compound 58) and (Compound 67) to (Compound 75).

[0096]

[16] According to the method, wherein

[0097] The component (A) is used in the form of a liquid containing the component (A) at a concentration of 0.1 to 1000 mM.

[0098]

[17] According to the method, wherein

[0099] The insect pest is an insect pest caused by an organism classified into the order Lepidoptera, Hemiptera, Coleoptera, Diptera, Orthoptera, Thysanoptera, Tyrannosaurus, Collembola, Acarina, or Stylophora.

[0100]

[18] According to the method, wherein

[0101] The insect pests are classified into the families of Plutella xylostella, Noctuidae, Pyralidae, Leafroller, Leafminer, Fruitborer, Gnaphalidae, Grassworm, Lightmoth, Lymantria, Cicadidae, Rice Pseudopsidae, Psyllidae, Aphididae, Aleyrodidae, Coccoidea, Miridae, Net Bugs, Pentatomidae, Longistidae, Scarabidae, Click Beetle, Coccinella, Cerambycidae, Chilophoridae, Curculionidae, Muscidae, Calliphoridae, Pests caused by organisms of the Sarcophagidae, Tachymycetes, Tephritidae, Gramomycetes, Ornithopoidea, Xiphophidae, Stigmidae, Coneheaded Grasshoppers, Thripidae, Thripidae, Thripidae, Acanthidae, Neotylenchidae, Acanthophoridae, Collembola, Tetranychus, Dermatophytidae, Acaridae, Sarcoptidae, Myxomycetes or Slugidae.

[0102]

[19] According to the method, wherein

[0103] The plant is a plant of the Poaceae family, the Solanaceae family, the Cucurbitaceae family, the Leguminosae family, the Cruciferae family, the Rosaceae family, the Moraceae family, the Malvaceae family, the Apiaceae family, the Liliaceae family, the Asteraceae family, the Amaranthaceae family, the Ericaceae family, the Vitaceae family, the Rutaceae family, the Rubiaceae family, the Oleaceae family, the Lauraceae family, the Anacardiaceae family, the Sapindaceae family or the Lamiaceae family. BRIEF DESCRIPTION OF THE DRAWINGS

[0104] [ Figure 1] is a graph showing the expression induction effect of insect pest resistance genes in Arabidopsis thaliana caused by glutamate derivatives. "Sor:" sorbitol, "Glu:" glutamate, "#1:" compound 1, "#34:" compound 34. "ns:" not significant. Time (0min or 30min) indicates the time from compound treatment to sample recovery. Statistical analysis was performed by Steel's test.

[0105] [ Figure 2 ] is a graph showing the pest feeding inhibitory effect in Arabidopsis thaliana caused by glutamic acid derivatives. The vertical axis represents the weight of the plant eaten by the pest. "#1:" Compound 1. "ns:" Not significant. Statistical analysis was performed by Steel's test.

[0106] [ Figure 3 ] is a graph showing the pest feeding inhibitory effect in Arabidopsis thaliana caused by glutamic acid derivatives. The vertical axis represents the weight increase rate of the pest. "#1:" Compound 1. "ns:" Not significant. Statistical analysis was performed by Steel's test.

[0107] [ Figure 4 ] is a graph showing the pest feeding inhibitory effect in Arabidopsis thaliana caused by glutamic acid derivatives. The vertical axis represents the weight increase rate of the pest. "#1:" Compound 1. "ns:" Not significant. Statistical analysis was performed by Steel's test.

[0108] [ Figure 5 ] is a graph showing the effect of glutamic acid derivatives on inhibiting feeding of pests on Japanese mustard. The vertical axis represents the ratio of the area damaged by pests (pest feeding area). DETAILED DESCRIPTION

[0109] Hereinafter, the present invention is described in detail.

[0110] <1> Active ingredients

[0111] In the present invention, the following component (A) is used:

[0112] (A) a compound represented by the following general formula (I),

[0113] Ingredient (A) is also referred to as the "active ingredient."

[0114] Component (A) is a compound represented by the following general formula (I). It should be noted that, for component (A), “R n " and "Rn" (n is a positive integer) can be used instead of each other.

[0115] [Chemical formula 1]

[0116]

[0117] In formula (I), n represents an integer of 1 to 3, that is, 1, 2 or 3.

[0118] In formula (I), X represents an interatomic bond, an oxygen atom (O), a nitrogen atom bonded to a hydrogen atom (NH), a nitrogen atom bonded to a methyl group (NMe), a sulfur atom (S), or a 4-phenoxy group. It should be noted that "4-phenoxy" as X means that the carbon bonded to (-CH2-)n is at the 1-position, and the O bonded to the carbon at the 4-position is at the R 3 Bonding was performed.

[0119] In formula (I), R 1 It represents a hydrogen atom (H), an amidine group or an acyl group.

[0120] In formula (I), R 2 Represents OR 4 or NHR 4 .

[0121] In formula (I), R 3 Represents C(=O)-R 5 , sulfonic acid (SO3H), phosphoric acid (PO3H2) or SO2R 6 .

[0122] R 4 It represents a hydrogen atom (H) or an optionally substituted alkyl group having 1 to 8 carbon atoms.

[0123] R 5 represents an optionally substituted alkyl group having 1 to 8 carbon atoms, an amino acid, a dipeptide, OR 7 or NR 8 R 9 .

[0124] R 6 represents a methyl group or an optionally substituted phenyl group.

[0125] R 7 It represents a hydrogen atom (H) or an alkyl group having 1 to 8 carbon atoms.

[0126] R 8 and R 9 Each independently represents a hydrogen atom (H), an optionally substituted alkyl group having 1 to 8 carbon atoms, or an optionally substituted phenyl group.

[0127] In one embodiment, n can be 2.

[0128] In one embodiment, X can be an interatomic bond.

[0129] In one embodiment, n is 2, X is an interatomic bond, and R 2 is hydroxyl group, R 3 C(=O)-R 5 .

[0130] In one embodiment, n is 2, X is an interatomic bond, and R 1 is a hydrogen atom, R 2 is hydroxyl group, R 3 C(=O)-R 5 , R 5 A group other than a hydroxyl group.

[0131] In one embodiment, n is 2, X is an interatomic bond, and R 1 is a group other than a hydrogen atom, R 2 is hydroxyl group, R 3 C(=O)-R 5 , R 5 It is hydroxyl.

[0132] In one embodiment, n is 2, X is an interatomic bond, and R 1 is a hydrogen atom, R 2 is a group other than a hydroxyl group, R 3 It is C(=O)-OH.

[0133] Unless otherwise specified, for component (A), X, n and R 1 ~R 9 Can be selected independently.

[0134] "Optionally substituted functional group" refers to the general term for substituted functional groups and unsubstituted functional groups. That is, for example, "optionally substituted alkyl" refers to the general term for substituted alkyl and unsubstituted alkyl. Substituted functional groups are also called "substituted functional groups", and unsubstituted functional groups are also called "unsubstituted functional groups". That is, for example, substituted alkyl is also called "substituted alkyl", and unsubstituted alkyl is also called "unsubstituted alkyl." It should be noted that, unless otherwise specified, "functional groups" that do not mention substitution refer to unsubstituted functional groups. That is, for example, "alkyl" that does not mention substitution refers to unsubstituted alkyl unless otherwise specified. The "number of carbon atoms" in the optionally substituted functional group refers to the number of carbon atoms of the functional group in the unsubstituted state (i.e., the number of carbon atoms excluding the number of carbon atoms of the substituent) unless otherwise specified, regardless of whether it is substituted or not. The description of unsubstituted functional groups can be applied to the parts other than the substituents in the substituted functional groups by analogy. That is, for example, the description of an unsubstituted alkyl group can be applied mutatis mutandis to the portion other than the substituent in the substituted alkyl group (ie, the alkyl portion).

[0135] "The functional group is substituted" means that one or more hydrogen atoms constituting the functional group are replaced by a substituent. "The functional group is substituted" is also referred to as "the functional group has a substituent." The number of hydrogen atoms substituted by substituents can be, for example, 1 to 5, 1 to 4, 1 to 3 or 1 to 2. As for the number of hydrogen atoms substituted by substituents, specifically, for example, it can be 1, 2, 3, 4 or 5. The number of hydrogen atoms substituted by substituents can be understood as the number of substituents possessed by the functional group. When two or more hydrogen atoms are substituted by substituents, the substituents are selected independently for each hydrogen atom. As hydrogen atoms substituted by substituents, hydrogen atoms bonded to carbon atoms, hydrogen atoms bonded to nitrogen atoms, and hydrogen atoms bonded to oxygen atoms can be cited. The hydrogen atom bonded to a carbon atom may be, for example, a hydrogen atom bonded to a terminal carbon atom, or it may not be. "Terminal carbon atom" refers to the carbon atom at the end of the carbon chain. When the carbon chain is branched, the end may be the end of any branch.

[0136] Examples of the acyl group include an optionally substituted alkylcarbonyl group, an optionally substituted alkenylcarbonyl group, an optionally substituted arylcarbonyl group, and an optionally substituted alkoxycarbonyl group.

[0137] As a component of R 1The substituents possessed by the functional group of the acyl group (for example, substituted alkyl, substituted alkenyl, substituted aryl or substituted alkoxy) include halogen atoms, hydroxyl groups, amino groups, carboxyl groups, aminocarbonyl groups, mercapto groups, optionally substituted aryl groups, optionally substituted heteroaryl groups, optionally substituted alkoxy groups, optionally substituted alkylamino groups, optionally substituted alkoxycarbonylamino groups, optionally substituted alkoxycarbonyl groups and optionally substituted alkylthio groups.

[0138] As R 4 , R 5 , R 8 or R 9 The substituents of the substituted alkyl group include a halogen atom, a hydroxyl group, an amino group, a guanidino group, a carboxyl group, an aminocarbonyl group, a mercapto group, an optionally substituted aryl group, an optionally substituted heteroaryl group, an optionally substituted alkoxy group, an optionally substituted alkylamino group, an optionally substituted alkoxycarbonylamino group, an optionally substituted alkoxycarbonyl group, and an optionally substituted alkylthio group.

[0139] As R 6 , R 8 or R 9 The substituents on the substituted phenyl group include a halogen atom, a hydroxyl group, an amino group, a carboxyl group, an aminocarbonyl group, a mercapto group, a nitro group, an optionally substituted aryl group, an optionally substituted heteroaryl group, an optionally substituted alkoxy group, an optionally substituted alkylamino group, an optionally substituted alkoxycarbonylamino group, an optionally substituted alkoxycarbonyl group, and an optionally substituted alkylthio group.

[0140] As a component of R 1 The substituent which the substituted aryl group has in the functional group of the acyl group includes a halogen atom, a hydroxyl group, an amino group, a carboxyl group and an alkyl group.

[0141] As R 4 , R 5 , R 8 or R 9 The substituent of the substituted aryl group in the substituted alkyl group includes a halogen atom, a hydroxyl group, an amino group, a carboxyl group and an alkyl group.

[0142] As R 6 , R 8 or R 9 The substituent of the substituted aryl group in the substituted phenyl group may be a halogen atom, a hydroxyl group, an amino group, a carboxyl group, or an alkyl group.

[0143] As a component of R 1 The substituent of the substituted heteroaryl group in the functional group of the acyl group may be a halogen atom, a hydroxyl group, an amino group, a carboxyl group, or an alkyl group.

[0144] As R 4 , R 5 , R 8 or R 9 The substituent of the substituted heteroaryl in the substituted alkyl group includes a halogen atom, a hydroxyl group, an amino group, a carboxyl group and an alkyl group.

[0145] As R 6 , R 8 or R 9 The substituent of the substituted heteroaryl group in the substituted phenyl group may be a halogen atom, a hydroxyl group, an amino group, a carboxyl group, or an alkyl group.

[0146] As a component of R 1 The substituent of the substituted alkoxy group in the functional group of the acyl group may be a halogen atom, a hydroxyl group, an amino group, a carboxyl group, an aminocarbonyl group, an aryl group, and a heteroaryl group.

[0147] As R 4 , R 5 , R 8 or R 9 The substituent of the substituted alkoxy group in the substituted alkyl group includes a halogen atom, a hydroxyl group, an amino group, a carboxyl group, an aminocarbonyl group, an aryl group, and a heteroaryl group.

[0148] As R 6 , R 8 or R 9 The substituent of the substituted alkoxy group in the substituted phenyl group may be a halogen atom, a hydroxyl group, an amino group, a carboxyl group, an aminocarbonyl group, an aryl group, and a heteroaryl group.

[0149] As a component of R 1 The substituent of the substituted alkoxycarbonyl group in the functional group of the acyl group may be a halogen atom, a hydroxyl group, an amino group, a carboxyl group, an aminocarbonyl group, an aryl group, and a heteroaryl group.

[0150] As R 4 , R 5 , R 8 or R 9 The substituent of the substituted alkoxycarbonyl group in the substituted alkyl group includes a halogen atom, a hydroxyl group, an amino group, a carboxyl group, an aminocarbonyl group, an aryl group and a heteroaryl group.

[0151] As R 6 , R 8 or R 9 The substituent of the substituted alkoxycarbonyl group in the substituted phenyl group may be a halogen atom, a hydroxyl group, an amino group, a carboxyl group, an aminocarbonyl group, an aryl group, and a heteroaryl group.

[0152] As a component of R 1The substituent of the substituted alkylamino group in the functional group of the acyl group includes a halogen atom, a hydroxyl group, an amino group, a carboxyl group, an aminocarbonyl group, an N-alkyl group, an aryl group, and a heteroaryl group.

[0153] As R 4 , R 5 , R 8 or R 9 The substituent of the substituted alkylamino group in the substituted alkyl group includes a halogen atom, a hydroxyl group, an amino group, a carboxyl group, an aminocarbonyl group, an N-alkyl group, an aryl group and a heteroaryl group.

[0154] As R 6 , R 8 or R 9 The substituent of the substituted alkylamino group in the substituted phenyl group includes a halogen atom, a hydroxyl group, an amino group, a carboxyl group, an aminocarbonyl group, an N-alkyl group, an aryl group, and a heteroaryl group.

[0155] As a component of R 1 The substituent of the substituted alkoxycarbonylamino group in the functional group of the acyl group may be a halogen atom, a hydroxyl group, an amino group, a carboxyl group, an aminocarbonyl group, an N-alkyl group, an aryl group, and a heteroaryl group.

[0156] As R 4 , R 5 , R 8 or R 9 The substituent of the substituted alkoxycarbonylamino group in the substituted alkyl group includes a halogen atom, a hydroxyl group, an amino group, a carboxyl group, an aminocarbonyl group, an N-alkyl group, an aryl group and a heteroaryl group.

[0157] As R 6 , R 8 or R 9 The substituent of the substituted alkoxycarbonylamino group in the substituted phenyl group may be a halogen atom, a hydroxyl group, an amino group, a carboxyl group, an aminocarbonyl group, an N-alkyl group, an aryl group, and a heteroaryl group.

[0158] The "N-alkyl group" refers to an alkyl group that replaces the hydrogen atom of an amino group.

[0159] Examples of the halogen atom include a fluorine atom, a chlorine atom, a bromine atom and an iodine atom.

[0160] Examples of the alkyl group include alkyl groups having 1 to 12 carbon atoms. Examples of the alkyl group include alkyl groups having 1 to 8 carbon atoms. Examples of the alkyl group include alkyl groups having 1 to 6 carbon atoms. Examples of the alkyl group include alkyl groups having 1 to 4 carbon atoms. The alkyl group may be linear, branched, or cyclic. Examples of the alkyl group having 1 to 8 carbon atoms include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, 2,3-dimethylpropyl, hexyl, heptyl, octyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl. Examples of the alkyl group having 1 to 6 carbon atoms include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, 2,3-dimethylpropyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl. Examples of the alkyl group having 1 to 4 carbon atoms include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, cyclopropyl, and cyclobutyl. The description of the alkyl group also applies to the N-alkyl group.

[0161] Examples of the alkenyl group include alkenyl groups having 1 to 6 carbon atoms. The alkenyl group may be linear or branched. Specific examples of the alkenyl group include vinyl, allyl, propenyl, butenyl, butadienyl, pentenyl, pentadienyl, hexenyl, and hexadienyl.

[0162] Examples of the aryl group include aryl groups having 6 to 14 carbon atoms. Examples of the aryl group include particularly aryl groups having 6 to 10 carbon atoms. Specific examples of the aryl group include phenyl, naphthyl, and fluorenyl.

[0163] “Heteroaryl” refers to an aryl group having at least one hetero atom selected from a nitrogen atom, an oxygen atom and a sulfur atom as an atom constituting a ring. Examples of the heteroaryl group include heteroaryl groups having 3 to 14 carbon atoms. Examples of the heteroaryl group include, in particular, heteroaryl groups having 4 to 10 carbon atoms. Examples of the heteroaryl group include, more particularly, heteroaryl groups having 4 to 9 carbon atoms. Specifically, examples of the heteroaryl group include furyl, pyrrolyl, oxazolyl, imidazolyl, pyrazolyl, pyranyl, indenyl, phenylthio, pyridyl, indolyl and quinolyl. Examples of the heteroaryl group include, in particular, imidazolyl and indolyl.

[0164] Examples of the alkoxy group include alkoxy groups having 1 to 6 carbon atoms. Examples of the alkoxy group include alkoxy groups having 1 to 4 carbon atoms. The alkoxy group may be linear or branched. Examples of the alkoxy group include methoxy, ethoxy, 1-propoxy, 2-propoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, 1-pentyloxy, 2-pentyloxy, 3-pentyloxy, 2-methyl-1-butoxy, 3-methyl-1-butoxy, 2-methyl-2-butoxy, 3-methyl-2-butoxy, 2,2-dimethyl-1-propoxy, 1-hexyloxy, 2-hexyloxy, and 3-hexyloxy. Examples of the alkoxy group include tert-butoxy.

[0165] The optionally substituted alkyl group is an alkyl group or a substituted alkyl group. The alkyl group is as described above. The description of the alkyl group can be applied mutatis mutandis to the alkyl group constituting the substituted alkyl group. The substituents constituting the substituted alkyl group are as described above. For example, as the optionally substituted alkyl group having 1 to 4 carbon atoms, in particular, methyl, ethyl, isopropyl, isobutyl, tert-butyl, cyclopropyl, cyclobutyl, benzyl, hydroxyethyl, hydroxypropyl (2-hydroxypropyl, etc.) can be mentioned.

[0166] The optionally substituted phenyl group is a phenyl group or a substituted phenyl group. The substituents constituting the substituted phenyl group are as described above. As the optionally substituted phenyl group, specifically, phenyl, hydroxyphenyl (2-, 3- or 4-hydroxyphenyl, etc.), chlorophenyl (2-, 3- or 4-chlorophenyl, etc.), dichlorophenyl (2,5-dichlorophenyl, etc.), fluorophenyl (2-, 3- or 4-fluorophenyl, etc.), nitrophenyl (2-, 3- or 4-nitrophenyl, etc.) can be cited.

[0167] The aryl group which may be substituted is an aryl group or a substituted aryl group. The aryl group is as described above. The description of the aryl group can be applied mutatis mutandis to the aryl group constituting the substituted aryl group. The substituent group constituting the substituted aryl group is as described above.

[0168] As the substituted aryl group, specifically, an alkyl aryl group that may be substituted (i.e., an alkyl aryl group, a substituted alkyl aryl group) may be mentioned. For the alkyl group, aryl group, and substituent group constituting the alkyl aryl group or the substituted alkyl aryl group, the description of the alkyl group, aryl group, and substituent group thereof may be applied mutatis mutandis, respectively. As the alkyl aryl group that may be substituted, specifically, a methylphenyl group (2-, 3-, or 4-methylphenyl group, etc.) may be mentioned.

[0169] Specific examples of the substituted aryl group include hydroxyphenyl (2-, 3-, or 4-hydroxyphenyl, etc.), chlorophenyl (2-, 3-, or 4-chlorophenyl, etc.), dichlorophenyl (2,5-dichlorophenyl, etc.), fluorophenyl (2-, 3-, or 4-fluorophenyl, etc.), and 2,3-dihydroxyindenyl.

[0170] The optionally substituted heteroaryl group is a heteroaryl group or a substituted heteroaryl group. The heteroaryl group is as described above. The heteroaryl group constituting the substituted heteroaryl group can be applied mutatis mutandis to the description of the heteroaryl group. The substituent group constituting the substituted heteroaryl group is as described above.

[0171] The optionally substituted alkoxy group is an alkoxy group or a substituted alkoxy group. The alkoxy group is as described above. The description of the alkoxy group can be applied mutatis mutandis to the alkoxy group constituting the substituted alkoxy group. The substituent group constituting the substituted alkoxy group is as described above.

[0172] As the substituted alkoxy group, specifically, an optionally substituted arylalkoxy group (i.e., an arylalkoxy group, a substituted arylalkoxy group) can be mentioned. For the aryl group, alkoxy group and substituent group constituting the arylalkoxy group or the substituted arylalkoxy group, the description of the aryl group, alkoxy group and the substituent group thereof can be applied mutatis mutandis, respectively. As the optionally substituted arylalkoxy group, specifically, a phenylmethoxy group can be mentioned.

[0173] Specific examples of the substituted alkoxy group include a hydroxyalkoxy group (such as a hydroxyethoxy group) and a trifluoromethoxy group.

[0174] The optionally substituted alkylamino group is an alkylamino group or a substituted alkylamino group. For the alkyl group constituting the alkylamino group, the description of the alkyl group can be applied mutatis mutandis. For the alkyl group and the substituent group constituting the substituted alkylamino group, the description of the alkyl group and its substituent group can be applied mutatis mutandis. For example, the number of carbon atoms of the alkyl group (e.g., 1 to 12, 1 to 6) can be understood as the number of carbon atoms of the optionally substituted alkylamino group (excluding the number of carbon atoms of the substituent group). As the substituted alkylamino group, specifically, there can be mentioned an optionally substituted carboxyalkylamino group (i.e., carboxyalkylamino group, substituted carboxyalkylamino group). The number of carbon atoms of the optionally substituted carboxyalkylamino group (excluding the number of carbon atoms of the substituent group) can be, for example, 2 to 13 or 2 to 7. As the carboxyalkylamino group, specifically, there can be mentioned carboxymethylamino group and 1-methylcarboxymethylamino group. As the substituted carboxyalkylamino group, specifically, there can be mentioned a carboxyalkylamino group substituted with a hydroxyl group, an amino group, a carboxyl group, a phenyl group, an indolyl group or an N-methyl group. More specifically, the substituted carboxyalkylamino group includes 1-(aminobutyl)carboxymethylamino, 1-methylcarboxymethylamino, 1-(indolylmethyl)carboxymethylamino, 1-(carboxymethyl)carboxymethylamino, 1-(1-hydroxyethyl)carboxymethylamino, 1-(hydroxymethyl)carboxymethylamino, 1-isobutylcarboxymethylamino, 1-benzylcarboxymethylamino and N-methylcarboxymethylamino.

[0175] The optionally substituted alkylcarbonyl group is an alkylcarbonyl group or a substituted alkylcarbonyl group. The description of the alkyl group constituting the alkylcarbonyl group can be applied mutatis mutandis. The description of the alkyl group and its substituent can be applied mutatis mutandis to the alkyl group constituting the substituted alkylcarbonyl group.

[0176] The optionally substituted alkenylcarbonyl group is an alkenylcarbonyl group or a substituted alkenylcarbonyl group. The description of the alkenyl group can be applied mutatis mutandis to the alkenyl group constituting the alkenylcarbonyl group. The description of the alkenyl group and its substituent can be applied mutatis mutandis to the alkenyl group and the substituent group constituting the substituted alkenylcarbonyl group.

[0177] The optionally substituted arylcarbonyl group is an arylcarbonyl group or a substituted arylcarbonyl group. The description of the aryl group can be applied mutatis mutandis to the aryl group constituting the arylcarbonyl group. The description of the aryl group and the substituent group constituting the substituted arylcarbonyl group can be applied mutatis mutandis to the aryl group and the substituent group thereof.

[0178] The optionally substituted alkoxycarbonyl group is an alkoxycarbonyl group or a substituted alkoxycarbonyl group. For the alkoxy group constituting the alkoxycarbonyl group, the description of the alkoxy group can be applied mutatis mutandis. For the alkoxy group and the substituent group constituting the substituted alkoxycarbonyl group, the description of the alkoxy group and its substituent group can be applied mutatis mutandis. As the optionally substituted alkoxycarbonyl group, specifically, indolylacetylmethoxycarbonyl, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, isobutoxycarbonyl, sec-butoxycarbonyl, tert-butoxycarbonyl (also called Boc), phenylmethoxycarbonyl, 9-fluorenylmethoxycarbonyl (also called Fmoc), 3-methylphenoxyacetyl, 3-chlorophenylmethoxycarbonyl, trifluoromethoxycarbonyl, 2,5-dichlorobenzoyl, benzyloxycarbonyl (also called Cb z) can be cited. Examples of the optionally substituted alkoxycarbonyl group include, in particular, a tert-butoxycarbonyl group, a 9-fluorenylmethoxycarbonyl group and a benzyloxycarbonyl group.

[0179] The optionally substituted alkoxycarbonylamino group is an alkoxycarbonylamino group or a substituted alkoxycarbonylamino group. For the alkoxy group (or alkoxycarbonyl group) constituting the alkoxycarbonylamino group, the description of the alkoxy group (or alkoxycarbonyl group) can be applied mutatis mutandis. For the alkoxy group (or alkoxycarbonyl group) and the substituent group constituting the substituted alkoxycarbonylamino group, the description of the alkoxy group (or alkoxycarbonyl group) and its substituent group can be applied mutatis mutandis. As the optionally substituted alkoxycarbonylamino group, specifically, tert-butoxycarbonylamino, 9-fluorenylmethoxycarbonylamino, and benzyloxycarbonylamino can be mentioned.

[0180] The optionally substituted alkylthio group is an alkylthio group or a substituted alkylthio group. For the alkyl group constituting the alkylthio group, the description of the alkyl group and the substituent group can be applied mutatis mutandis. For the alkyl group and the substituent group constituting the substituted alkylthio group, the description of the alkyl group and the substituent group can be applied mutatis mutandis. As the optionally substituted alkylthio group, specifically, methylthio can be mentioned.

[0181] As the acyl group, in particular, alkylcarbonyl groups which may be substituted and alkoxycarbonyl groups which may be substituted are mentioned. As the acyl group, specifically, acetyl, propionyl, butyryl (butyryl) (also known as butanoyl), isobutyryl, valeryl (also known as pentanoyl), isovaleryl, pivaloyl, hexanoyl, acryloyl, methacryloyl, crotonyl, isocrotonyl, cyclopropanoyl, cyclobutanoyl, cyclopentanoyl, cyclohexanoyl, benzoyl, pteroyl, aminoacetyl, 2-oxo-3-methylbutyryl, and the alkoxycarbonyl groups which may be substituted as mentioned above are mentioned. As the acyl group, in particular, acetyl, tert-butoxycarbonyl, 9-fluorenylmethoxycarbonyl, benzyloxycarbonyl are mentioned. As the acyl group, specifically, acyl groups corresponding to amino acids are mentioned. "Acyl groups corresponding to amino acids" refer to groups obtained by removing the OH of the carboxyl group of amino acids. For example, the acyl group corresponding to glycine is aminoacetyl. As described below for amino acids.

[0182] As R 5 The term "amino acid" refers to an amino acid that is bonded to R 3 C(=O)-bonded amino acids.

[0183] As R 5 Examples of the amino acid include amino acids bonded via an amino group, amino acids bonded via a carboxyl group, amino acids bonded via a hydroxyl group, amino acids bonded via a thiol group, and amino acids bonded via an amide group. 5 The amino acids include amino acids bonded via an amino group.

[0184] "Amino acid bonded via the amino group" means an amino acid bonded to R via the nitrogen atom of the amino group. 3 It should be noted that when an amino acid has two or more amino groups, any of these amino groups can be used to bind to R 3 For example, the α-amino group can be used to bond with R 3 The C(=O) bonding, ε amino group can be used to bond with R 3 The bonding of C(=O) is shown in FIG.

[0185] The term "amino acid bonded via the carboxyl group" means an amino acid bonded to R via the oxygen atom of the OH group of the carboxyl group. 3It should be noted that when an amino acid has two or more carboxyl groups, any of these carboxyl groups can be used to bind to R 3 For example, the α-carboxyl group can be used to bond with R 3 The C(=O) bonding, other carboxyl groups can be used to bond with R 3 The bonding of C(=O) is shown in FIG.

[0186] The term "amino acid bonded via a hydroxyl group" means an amino acid bonded to R via the oxygen atom of the hydroxyl group. 3 C(=O)-bonded amino acids.

[0187] The term "amino acid bonded via a thiol group" refers to an amino acid bonded to R via the sulfur atom of the thiol group. 3 C(=O)-bonded amino acids.

[0188] The term "amino acid bonded via an amide group" refers to an amino acid bonded to R via the nitrogen atom of the amide group. 3 C(=O)-bonded amino acids.

[0189] As amino acids, basic amino acids such as lysine, ornithine, arginine, histidine, citrulline, diaminobutyric acid, diaminopropionic acid, aliphatic amino acids such as isoleucine, alanine, valine, leucine, glycine, amino acids such as hydroxymonoaminocarboxylic acids such as threonine and serine, cyclic amino acids such as proline (also referred to as "imido acids"), aromatic amino acids such as phenylalanine, tyrosine, tryptophan, sulfur-containing amino acids such as cysteine, cystine, methionine, acidic amino acids such as glutamic acid and aspartic acid, amino acids having amide groups in side chains such as glutamine and asparagine can be cited. As amino acids, norvaline, norleucine, α-aminobutyric acid, γ-aminobutyric acid, hydroxyproline, tert-leucine, and sarcosine can be cited. Amino acids may or may not have substituents on their amino and / or carboxyl groups. That is, "amino acids" include those having substituents on their amino and / or carboxyl groups unless otherwise specified. That is, as amino acids, amino acids having substituents on their amino and / or carboxyl groups can be cited. As the substituents possessed by the amino group in the amino acid, there can be mentioned an alkoxycarbonyl group which may be substituted, and an alkyl group which may be substituted. That is, the amino group in the amino acid may constitute, for example, an alkoxycarbonylamino group which may be substituted or an alkylamino group which may be substituted. As the substituents possessed by the amino group in the amino acid, there can be mentioned, in particular, tert-butoxycarbonyl, 9-fluorenylmethoxycarbonyl, benzyloxycarbonyl, and acetyl. As the substituents possessed by the carboxyl group in the amino acid, there can be mentioned an alkyl group which may be substituted, and an amino group. That is, the carboxyl group in the amino acid may constitute, for example, an alkoxycarbonyl group which may be substituted or an aminocarbonyl group. As the substituents possessed by the carboxyl group in the amino acid, there can be mentioned, in particular, a methyl group, an ethyl group, a tert-butyl group, and a benzyl group.

[0190] Unless otherwise specified, the amino acid may be a D-form, an L-form, or a combination thereof. The ratio of the D-form to the L-form in the combination is not particularly limited. As for the ratio of the D-form or the L-form in the combination, for example, it may be 20 to 80%, 30 to 70%, 40 to 60%, or 45 to 55% in terms of molar ratio. The amino acid may be particularly an L-form. It should be noted that, when selecting an amino acid in the form of the D-form or the L-form, it is sufficient to use the amino acid in the form of the D-form or the L-form, and the use of the amino acid in the form of the L-form or the D-form in combination is not excluded.

[0191] As R 5 The "dipeptide" is a peptide that is bonded to R 3 C(=O)-bonded dipeptide.

[0192] As R 5 Examples of the dipeptide include a dipeptide bonded via an amino group, a dipeptide bonded via a carboxyl group, a dipeptide bonded via a hydroxyl group, a dipeptide bonded via a thiol group, and a dipeptide bonded via an amide group. 5 In particular, there can be mentioned dipeptides bonded via an amino group.

[0193] "Dipeptide bonded via the amino group" means that the dipeptide is bonded to R via the nitrogen atom of the amino group. 3 It should be noted that when the dipeptide has two or more amino groups, any of these amino groups can be used to bond with R 3 For example, the α-amino group can be used to bond with R 3 The C(=O) bonding, ε amino group can be used to bond with R 3 The bonding of C(=O) is shown in FIG.

[0194] The "dipeptide bonded via the carboxyl group" means that the dipeptide is bonded to R via the oxygen atom of the OH of the carboxyl group. 3 It should be noted that when the dipeptide has two or more carboxyl groups, any of these carboxyl groups can be used to bond with R 3 For example, the α-carboxyl group can be used to bond with R 3 The C(=O) bonding, other carboxyl groups can be used to bond with R 3 The bonding of C(=O) is shown in FIG.

[0195] The term "dipeptide bonded via a hydroxyl group" means that the dipeptide is bonded to R via the oxygen atom of the hydroxyl group. 3 C(=O)-bonded dipeptide.

[0196] The term "dipeptide bonded via a thiol group" means that the dipeptide is bonded to R via the sulfur atom of the thiol group. 3 C(=O)-bonded dipeptide.

[0197] The term "dipeptide bonded via an amide group" refers to a dipeptide bonded via the nitrogen atom of the amide group to R 3 C(=O)-bonded dipeptide.

[0198] For the amino acids constituting the dipeptide, the description of the amino acids can be applied mutatis mutandis. The two amino acids constituting the dipeptide can be the same amino acid or different amino acids. Specifically, Val-Val, Glu-Val, Cys-Gly, Glu-Glu, Glu-Gly, Gly-Gly, Glu-Phe, and Glu-Pro can be cited. The amino group and / or carboxyl group of the dipeptide may or may not have a substituent. That is, "dipeptide" includes a dipeptide having a substituent in its amino group and / or carboxyl group unless otherwise specified. For the substituents in the amino group and / or carboxyl group of the dipeptide, the description of the substituents in the amino group and / or carboxyl group of the amino acids can be applied mutatis mutandis.

[0199] As X, n and R 1 ~R 9 Specifically, X, n and R of the compounds represented by the following formulas (Compound 1) to (Compound 66) and the compounds represented by the following formulas (Compound 67) to (Compound 75) can be cited. 1 ~R 9 That is, in terms of X, n and R 1 ~R 9 Specifically, for example, X, n and R can be selected from the compounds represented by the following formulas (Compound 1) to (Compound 66) and the compounds represented by the following formulas (Compound 67) to (Compound 75). 1 ~R 9 .

[0200] As component (A), specifically, compounds represented by the following formulas (Compound 1) to (Compound 58) and compounds represented by the following formulas (Compound 67) to (Compound 75) can be cited. As component (A), in particular, compounds represented by the following formulas (Compound 1) to (Compound 58) can be cited. In addition, as component (A), specifically, compounds represented by the following formulas (Compound 59) to (Compound 66) can be cited.

[0201] [Chemical formula 2]

[0202]

[0203] [Chemical formula 3]

[0204]

[0205] [Chemical formula 4]

[0206]

[0207] [Chemical formula 5]

[0208]

[0209] [Chemical formula 6]

[0210]

[0211] [Chemical formula 7]

[0212]

[0213] [Chemical formula 8]

[0214]

[0215] [Chemical formula 9]

[0216]

[0217] When component (A) can form salt, component (A) can be used as free form, can be used as salt, can be used as a combination thereof. That is, the term "component (A)" can refer to component (A) or its salt or a combination thereof in free form unless otherwise specified. "Free form" refers to a mode in which a salt is not formed. Salt is not particularly limited as long as it does not impair the effect of the present invention. For example, as salts for acidic groups such as carboxyl groups, ammonium salts, salts with alkali metals such as sodium and potassium, salts with alkaline earth metals such as calcium and magnesium, aluminum salts, zinc salts, salts with organic amines such as triethylamine, ethanolamine, morpholine, tetrahydropyrrole, piperidine, piperazine, dicyclohexylamine, and salts with basic amino acids such as arginine and lysine can be cited. In addition, as the salt for basic groups such as amino, salts with inorganic acids such as hydrochloric acid, sulfuric acid, phosphoric acid, nitric acid, and hydrobromic acid, salts with organic carboxylic acids such as acetic acid, citric acid, benzoic acid, maleic acid, fumaric acid, tartaric acid, succinic acid, tannic acid, butyric acid, hyaluronic acid, pamoic acid, enanthic acid, capric acid, theochloroic acid, salicylic acid, lactic acid, oxalic acid, mandelic acid, and malic acid, and salts with organic sulfonic acids such as methanesulfonic acid, benzenesulfonic acid, and p-toluenesulfonic acid can be enumerated. As salt, one salt can be used, and two or more salts can be used in combination.

[0218] In addition, when component (A) can form a hydrate, component (A) can be used as a non-hydrate, can be used as a hydrate, and can be used as a combination thereof. That is, the term "component (A)" (for example, "component (A) in a free form", "salt of component (A)") can include a non-hydrate and a hydrate unless otherwise specified.

[0219] Component (A) may be in any form such as ions when used.

[0220] As component (A), one component may be used, or two or more components may be used in combination. When two or more components are selected as component (A), the "amount" or "concentration" of component (A) may refer to the total amount or total concentration of the selected components unless otherwise specified.

[0221] As component (A), commercial products can be used, and those obtained by suitable manufacture can be used. The manufacturing method of component (A) is not particularly limited. Component (A) can be manufactured by, for example, a known method. As for component (A), specifically, for example, it can be manufactured by chemical synthesis, enzyme reaction, fermentation method, extraction method or a combination thereof. Component (A) may be purified to the desired degree or not. That is, as component (A), a purified product can be used, or a raw material containing component (A) can be used. As a raw material containing component (A), specifically, for example, fermentation products such as culture solution, bacterial cells, culture supernatant, etc. obtained by culturing a microorganism having the production capacity of the component (A), agricultural, aquatic and livestock products containing the component (A) and their processed products can be cited. As a processed product, a processed product obtained by concentrating, diluting, drying, separating, extracting, purifying and other treatments of raw materials such as such fermentation products can be cited. As component (A), for example, a raw material having a content of component (A) of 1% (w / w) or more, 5% (w / w) or more, 10% (w / w) or more, 30% (w / w) or more, 50% (w / w) or more, 70% (w / w) or more, 90% (w / w) or more, or 95% (w / w) or more can be used.

[0222] By utilizing the active ingredient, specifically, by applying the active ingredient to the plant, for example, it is possible to induce pest resistance in the plant, that is, the effect of inducing pest resistance in the plant can be obtained. This effect is also referred to as an "insect pest resistance inducing effect." Therefore, the active ingredient can be used, for example, to induce pest resistance in the plant. "Pest resistance" can refer to resistance against insect pests, specifically, it can refer to the property of reducing the degree of insect pests. "Inducing pest resistance in plants" can be used interchangeably with "imparting pest resistance to plants" or "improving pest resistance in plants."

[0223] By utilizing the active ingredient, specifically, by applying the active ingredient to the plant, for example, pests of the plant can be controlled, that is, an effect of controlling pests of the plant can be obtained. This effect is also referred to as a "pest control effect." Therefore, the active ingredient can be used, for example, for controlling pests of the plant. In particular, the pest control effect can be obtained by inducing pest resistance in the plant. Therefore, the pest control effect can be an example of an effect of inducing pest resistance. "Control of pests" can be used interchangeably with "reduction of pests", "reduction of pests" or "prevention of pests".

[0224] By utilizing the active ingredient, specifically, by applying the active ingredient to the plant, for example, the cultivation performance of the plant can be improved, that is, the effect of improving the cultivation performance of the plant can be obtained. This effect is also referred to as "the effect of improving the cultivation performance." In particular, the effect of improving the cultivation performance can be obtained by inducing the insect pest resistance of the plant and / or controlling the insect pests of the plant. Therefore, the effect of improving the cultivation performance can be an example of the effect of inducing insect pest resistance or the effect of controlling insect pests. Examples of the improvement of the cultivation performance of the plant include the increase in the yield of the plant, the improvement in the growth and development of the plant, and the improvement in the survival rate of the plant. As an example of the improvement of the cultivation performance of the plant, in particular, the increase in the yield of the plant can be cited.

[0225] The type of plant is not particularly limited as long as it can be protected from insect damage.

[0226] Plants may be woody plants or herbaceous plants. Examples of plants include Gramineae (rice, barley, wheat, corn, sorghum, millet, sugarcane, oats, zoysia, pearl millet, tamarind, fonio millet, etc.), Solanaceae (tomato, sweet pepper, eggplant, potato, tobacco, etc.), Cucurbitaceae (cucumber, melon, pumpkin, etc.), Leguminosae (pea, soybean, kidney bean, alfalfa, peanut, broad bean, cowpea, lentil, chickpea, clover, groundnut, Bambara peanut, etc.), Cruciferae (radish, cabbage, cabbage, komatsuna, cauliflower, green cabbage, Arabidopsis, etc.), Rosaceae (strawberry, apple, pear, peach, etc.), Moraceae (mulberry, etc.), Malvaceae (cotton, etc.), Apiaceae (carrot, parsley, celery, etc.), Liliaceae (leek, onion, asparagus, etc.), Asteraceae (burdock, sunflower, chrysanthemum, chamomile, prickly ash, lettuce, etc.), Amaranthaceae (beet, etc.), Ericaceae (blueberry, cranberry, etc.), Vitaceae (grape, etc.), Rutaceae (Wenzhou mandarin orange, lemon, pomelo, etc.), Rubiaceae (coffee tree, etc.), Oleaceae (olive, etc.), Lauraceae (avocado, etc.), Anacardiaceae (mango, cashew tree, etc.), Sapindaceae (lychee, etc.), Lamiaceae (five-color sedge, etc.).

[0227] The plants may be one kind of plant or two or more kinds of plants.

[0228] "Insect damage" may refer to damage caused by insects. Examples of insect damage include insect feeding (i.e., feeding of plants by insects).

[0229] The types of pests are not particularly limited as long as they can cause pest damage.

[0230] Examples of pests include agricultural pests.

[0231] Specific examples of pests include those classified into the order Lepidoptera (Plutella xylostella, Noctuidae, Pyralidae, Leafroller, Leafminer, Fruitborer, Lycopodiidae, Psoralea, Leptidae, Leptidae, Lymantria, etc.), the order Hemiptera (Cicodermidae, Pachyphidae, Psyllidae, Aphididae, Aleyrodidae, Coccoidea, Miridae, Lycopodidae, Pentatomidae, Pentatomidae, etc.), the order Coleoptera (Scarabidae, Click Beetles, Coccinellidae, Cerambycidae, Chilophoridae, Curculionidae, etc.), the order Diptera (Muscidae, Calliphoridae, Sarcophagidae), Organisms of the order (family Acipenseridae, Acipenseridae, Tephritidae, Gramineoidea, Ornithopoeidae, etc.), Orthoptera (Acipenseridae, Acipenseridae, Coneheaded Acrididae, etc.), Thysanoptera (Thripsidae, Thripidae, Thripidae, etc.), Cynomolgus (Aglajidae, Neotylenchidae, etc.), Collembola (Collembodae, Echinopsidae, etc.), Acarina (Tetranychus, Dermatophytidae, Acaridae, Sarcoptes, etc.), and Stylophora (Myxopodidae, Basiliidae, etc.).

[0232] Specific examples of the pests of the order Lepidoptera include the striped stem borer, the rice leaf folder, the rice hesperid, the greater stem borer, the oriental armyworm, the rice stem borer, the armyworm, the bean pod borer, the bean pod borer, the bean roller, the soybean borer, the bean fan borer, the yellow cutworm, the small cutworm, the sweet potato moth, the eight-character cutworm, the tobacco budworm, the cotton bollworm, the cabbage armyworm, the beet armyworm, the diamondback moth, the rapa butterfly, the European white butterfly, the cabbage borer, and the black-spotted silver moth. Specific examples of the pests of the order Hemiptera include brown planthopper, white-backed planthopper, gray planthopper, black-tailed leafhopper, rice electric leafhopper, red-striped blind bug, striped red-whiskered blind bug (Trigon otyluscaelestialium), middle rice margin bug, black-whiskered rice green stink bug, rice green stink bug, rice brown stink bug (Lagynotomus elongatus), rice black stink bug, two-star stink bug, Japanese two-star stink bug (Eysarcoris lewisi), broad two-star stink bug, Togo hemipterus, rice thorn margin stink bug, wall stink bug, tea-winged stink bug, spotted palp stink bug, Taiwan leek aphid, cereal aphid, corn aphid, soybean aphid. As pests of Coleoptera, specifically, coffee fruit borer, rice water weevil, rice mud beetle, rice scale weevil, horn comb claw click beetle, Melanotus foltnumi, bronze beetle, bronze beetle, Japanese bean beetle, Asian garden beetle, Mexican bean beetle, black striped wheat leaf beetle, potato beetle, eggplant twenty-eight-spotted ladybird, Harmonia axyridis, red copper beetle, purple green beetle (Mimelatestaceipes), yellow melon, yellow curved striped vegetable flea beetle can be mentioned. As pests of Diptera, specifically, rice stalk flyminer, rice leafminer (HydrelliagriseolaFallen), wheat red midge, gray ground fly, pepper dry gall midge, bean stalk black flyminer, three leaf leafminer, American leafminer, lettuce South American leafminer, tomato leafminer can be mentioned. As pests of Orthoptera, specifically, small-winged rice grasshopper and Japanese rice grasshopper can be mentioned. As the pests of the order Thysanoptera, specifically, rice thrips and palm thrips can be mentioned. As the pests of the order of nematodes, specifically, root-knot nematodes, brevis-bodied nematodes and cyst nematodes can be mentioned. As the pests of the order of Collembola, specifically, Onychiurus pseudarmatus yagii and Onychiurus watanabei Matsumoto can be mentioned. As the pests of the order of Acarina, specifically, leaf claw mites, two-spotted spider mites, spider mites of Kanzawa, tyrophagous mites and two-leaved tarsonemes can be mentioned. As the pests of the order of stalked eyes, specifically, snails and slugs can be mentioned.

[0233] As the pests, one kind of pest may be targeted, or two or more kinds of pests may be targeted.

[0234] The pest resistance induction effect can be, for example, 2+That is, the Ca signal transduction was increased when the active ingredient was used compared to when the active ingredient was not used. 2+ In the case of signal transduction, there is a possibility that the active ingredient can induce pest resistance. 2+ Signal transduction can be confirmed, for example, by calcium imaging using a calcium indicator or a calcium-sensitive fluorescent protein. Specifically, for example, in a recombinant plant modified to express a calcium-sensitive protein, Ca can be confirmed by calcium imaging. 2+ Signal transduction. Calcium-sensitive fluorescent proteins include Cameleon, TN-XL, GCaMP3, and G-GECO. Detection of signals (e.g., fluorescence) in calcium imaging can be performed using a detector according to the type of signal, such as a fluorescence detector. Specifically, calcium imaging can be performed, for example, by the steps described in the embodiments.

[0235] The pest resistance induction effect can be confirmed, for example, by the expression of pest resistance genes as an indicator. That is, when the expression of pest resistance genes is increased when the active ingredient is used, there is a possibility of obtaining the pest resistance induction effect through the active ingredient. As an insect pest resistance gene, the AtOPR3 gene can be cited. The AtOPR3 gene is a gene encoding a 12-oxophytodienoate reductase involved in the biosynthesis of jasmonic acid. The enhancement of gene expression can be confirmed, for example, by measuring the transcription amount of the gene (for example, the amount of mRNA), the translation amount of the gene (for example, the amount of protein encoded by the gene) or the activity of the protein encoded by the gene. As a method for measuring the amount of mRNA, Northern hybridization and qPCR can be cited. As a method for measuring the amount of protein, Western blotting can be cited. The method for measuring the activity of the protein can be appropriately selected according to various conditions such as the type of protein of the object.

[0236] The pest resistance inducing effect can be confirmed, for example, by using the pest control effect as an index. That is, when the pest control effect is obtained by the active ingredient, it can be determined that the pest resistance inducing effect is obtained by the active ingredient.

[0237] The pest control effect can be confirmed, for example, by using the degree of pest damage (e.g., the amount of food consumed by pests on plants) as an indicator. That is, when the degree of pest damage on plants (e.g., the amount of food consumed by pests on plants) is reduced when the active ingredient is used compared to when the active ingredient is not used, it can be determined that the pest control effect is obtained by the active ingredient.

[0238] The pest resistance inducing effect or pest control effect can be confirmed, for example, by using the effect of improving cultivation results as an index. That is, when the cultivation results are improved by the active ingredient, it can be determined that the pest resistance inducing effect or pest control effect is obtained by the active ingredient.

[0239] The effect of improving the cultivation performance can be confirmed, for example, by using the cultivation performance (e.g., yield, growth, or survival rate) of the plant as an indicator. That is, when the cultivation performance (e.g., yield, growth, or survival rate) of the plant is improved when the active ingredient is used compared to when the active ingredient is not used, it can be determined that the cultivation performance improvement effect is obtained by the active ingredient.

[0240] <2> Compositions of the present invention

[0241] The composition of the present invention contains an active ingredient (ie, the ingredient (A)).

[0242] The composition of the present invention can be applied to plants for use. The use of the composition of the present invention is described in detail in "the method of the present invention". The composition of the present invention can be used, for example, to obtain the effects exemplified above.

[0243] By using the composition of the present invention, specifically, by applying the composition of the present invention to plants, for example, it is possible to induce pest resistance in plants, that is, to obtain a pest resistance induction effect. Therefore, the composition of the present invention can be, for example, a composition for inducing pest resistance in plants. The composition for inducing pest resistance in plants is also referred to as a "plant pest resistance inducer."

[0244] By utilizing the composition of the present invention, specifically, by applying the composition of the present invention to plants, for example, plant pests can be controlled, that is, a pest control effect can be obtained. Therefore, the composition of the present invention can be, for example, a composition for plant pest control. The composition for plant pest control is also referred to as a "plant pest control agent." The composition for plant pest control can be an example of a composition for inducing plant pest resistance.

[0245] By utilizing the composition of the present invention, specifically, by applying the composition of the present invention to plants, for example, the cultivation performance of the plants can be improved, that is, the cultivation performance improvement effect can be obtained. Therefore, the composition of the present invention can be, for example, a composition for improving the cultivation performance of plants. The composition for improving the cultivation performance of plants is also referred to as a "plant cultivation performance improver." The composition for improving the cultivation performance of plants can be an example of a composition for inducing pest resistance in plants or a composition for controlling pests in plants.

[0246] The use of the composition of the present invention as exemplified above may be useful, for example, in the field of agronomy and horticulture. Therefore, the composition of the present invention can be used, for example, in the field of agronomy and horticulture. That is, the composition of the present invention may be, for example, an agronomy and horticulture composition. Specifically, for example, the composition of the present invention may be an agronomy and horticulture composition used in the use of the composition of the present invention as exemplified above.

[0247] The composition of the present invention can be provided, for example, as a pesticide. In addition, the composition of the present invention can be provided, for example, as a fertilizer.

[0248] As for the composition of the composition of the present invention, as long as the composition of the present invention contains active ingredients and can obtain the desired effect, there is no particular limitation. As for the type and content of the components contained in the composition of the present invention, they can be appropriately selected according to various conditions such as the type of the object, the cultivation method of the object, the growth and development stage of the object, the purpose of the composition of the present invention, and the mode of use of the composition of the present invention.

[0249] The composition of the present invention may be composed of active ingredients, or may contain ingredients other than active ingredients. As ingredients other than active ingredients, for example, ingredients commonly used in pesticides, fertilizers, medicines, etc. may be cited. As such ingredients, specifically, for example, additives such as excipients, binders, disintegrants, lubricants, stabilizers, diluents, surfactants, spreaders, pH adjusters, water, alcohols, vitamins, and minerals may be cited. As spreaders, specifically, for example, APPROACH BI TM (Kao Co., Ltd.), MIXPOWER TM (SYNGENTAJAPAN (Co., Ltd.)), SQUASH TM (MARUWA BIOCHEMICAL (Co., Ltd.)). As ingredients other than the active ingredient, one ingredient may be used, or two or more ingredients may be used. The composition of the present invention may be formulated as appropriate. The dosage form of the composition of the present invention is not particularly limited. The dosage form of the composition of the present invention may be appropriately selected based on various conditions such as the method of utilizing the composition of the present invention. Examples of the dosage form include liquids, suspensions, powders, tablets, pills, capsules, and pastes.

[0250] The content of the active ingredient in the composition of the present invention is more than 0% (w / w) and is 100% (w / w) or less. The content of the active ingredient in the composition of the present invention may be, for example, 20 ppm (w / w) or more, 50 ppm (w / w) or more, 100 ppm (w / w) or more, 200 ppm (w / w) or more, 500 ppm (w / w) or more, 1000 ppm (w / w) or more, 2000 ppm (w / w) or more, 5000 ppm (w / w) or more, 1% (w / w) or more, 2% (w / w) or more, 5% (w / w) or more, 10% (w / w) or more, 20% (w / w) or more, 30% (w / w) or more, 50% (w / w) or more, or 70% (w / w) or more. w) or more, and can be 100% (w / w) or less, less than 100% (w / w), 99.9% (w / w) or less, 90% (w / w) or less, 70% (w / w) or less, 50% (w / w) or less, 30% (w / w) or less, 20% (w / w) or less, 10% (w / w) or less, 5% (w / w) or less, 2% (w / w) or less, 1% (w / w) or less, 5000ppm (w / w) or less, 2000ppm (w / w) or less, 1000ppm (w / w) or less, or 500ppm (w / w) or less, and can be a non-contradictory combination of these. The content of the active ingredient in the composition of the present invention can be specifically, for example, 20 ppm (w / w) to 50 ppm (w / w), 50 ppm (w / w) to 100 ppm (w / w), 100 ppm (w / w) to 1000 ppm (w / w), 1000 ppm (w / w) to 1% (w / w), 1% (w / w) to 10% (w / w), 10% (w / w) to 30% (w / w), 30% (w / w) to 50% (w / w), 50% (w / w) to 70% (w / w) or 70% (w / w) to 99.9% (w / w). The content of the active ingredient in the composition of the present invention may be, for example, 20 ppm (w / w) to 99.9% (w / w), 100 ppm (w / w) to 99.9% (w / w), 1000 ppm (w / w) to 99.9% (w / w), 1% (w / w) to 99.9% (w / w), 10% (w / w) to 99.9% (w / w), 100 ppm (w / w) to 99.9% (w / w), ~50% (w / w), 100ppm (w / w) ~ 10% (w / w), 100ppm (w / w) ~ 1% (w / w), 1000ppm (w / w) ~ 50% (w / w), 10 00ppm (w / w) ~ 10% (w / w), 1000ppm (w / w) ~ 1% (w / w), 1% (w / w) ~ 50% (w / w) or 1% (w / w) ~ 10% (w / w).

[0251] The content of the active ingredient in the composition of the present invention can be, for example, 0.1mM or more, 0.2mM or more, 0.5mM or more, 1mM or more, 2mM or more, 5mM or more, 10mM or more, 20mM or more, 50mM or more, 100mM or more, 200mM or more, or 500mM or more, and can be 1000mM or less, 500mM or less, 200mM or less, 100mM or less, 50mM or less, 20mM or less, 10mM or less, 5mM or less, 2mM or less, or 1mM or less, and can be any non-contradictory combination of these. The content of the active ingredient in the composition of the present invention may be, for example, 0.1 to 0.2 mM, 0.2 to 0.5 mM, 0.5 to 1 mM, 1 to 2 mM, 2 to 5 mM, 5 to 10 mM, 10 to 20 mM, 20 to 50 mM, 50 to 100 mM, 100 to 200 mM, 200 to 500 mM or 500 to 1000 mM. The content of the active ingredient in the composition of the present invention may be, for example, 0.1 to 1000 mM, 0.5 to 500 mM or 2 to 200 mM.

[0252] In addition, the content of the active ingredient in the composition of the present invention can be set, for example, so that the concentration of the active ingredient becomes a given range when the composition of the present invention is used. The concentration of the active ingredient when the composition of the present invention is used is also referred to as "the use concentration of the active ingredient" or "the application concentration of the active ingredient." The use concentration of the active ingredient can be particularly the concentration of the composition of the present invention when it is used in the form of a liquid.

[0253] The concentration of the active ingredient used may be, for example, 0.1 mM or more, 0.2 mM or more, 0.5 mM or more, 1 mM or more, 2 mM or more, 5 mM or more, 10 mM or more, 20 mM or more, 50 mM or more, 100 mM or more, 200 mM or more or 500 mM or more, and may be 1000 mM or less, 500 mM or less, 200 mM or less, 100 mM or less, 50 mM or less, 20 mM or less, 10 mM or less, 5 mM or less, 2 mM or less or 1 mM or less, and may be any non-contradictory combination of these. The concentration of the active ingredient used may be, for example, 0.1 to 0.2 mM, 0.2 to 0.5 mM, 0.5 to 1 mM, 1 to 2 mM, 2 to 5 mM, 5 to 10 mM, 10 to 20 mM, 20 to 50 mM, 50 to 100 mM, 100 to 200 mM, 200 to 500 mM or 500 to 1000 mM. The concentration of the active ingredient used may be, for example, 0.1 to 1000 mM, 0.5 to 500 mM or 2 to 200 mM.

[0254] It should be noted that the amount of the active ingredient (e.g., content (concentration), usage amount) is the amount calculated based on the amount of the active ingredient itself in the raw material when using a raw material containing the active ingredient. In addition, the amount of the active ingredient (e.g., content (concentration), usage amount) is the amount calculated based on the value obtained by converting the mass of the salt or hydrate into the mass of the free form of equimolar when the active ingredient forms a salt or hydrate.

[0255] The active ingredient and other ingredients may be mixed with each other and included in the composition of the present invention, or may be included in the composition of the present invention separately or in any combination.

[0256] <3> Method of the present invention

[0257] The method of the present invention includes a method of applying an active ingredient (ie, the ingredient (A)) to a plant. The method of the present invention can be carried out, for example, to obtain the effects exemplified above.

[0258] By implementing the method of the present invention, specifically, by applying the active ingredient to the plant, for example, the pest resistance of the plant can be induced, that is, the pest resistance induction effect can be obtained. Therefore, the method of the present invention can be, for example, a method for inducing pest resistance of the plant.

[0259] By implementing the method of the present invention, specifically, by applying the active ingredient to the plant, for example, the plant pests can be controlled, that is, the pest control effect can be obtained. Therefore, the method of the present invention can be, for example, a method for controlling plant pests. The method for controlling plant pests can be an example of a method for inducing plant pest resistance.

[0260] By implementing the method of the present invention, specifically, by applying the active ingredient to the plant, for example, the cultivation performance of the plant can be improved, that is, the cultivation performance improvement effect can be obtained. Therefore, the method of the present invention can be, for example, a method for improving the cultivation performance of the plant. The method for improving the cultivation performance of the plant can be an example of a method for inducing insect pest resistance in the plant or a method for controlling insect pests in the plant.

[0261] The active ingredient can be applied to plants, for example, using the composition of the present invention (i.e., by applying the composition of the present invention). That is, one form of the method of the present invention can be, for example, a method comprising applying the composition of the present invention to plants. "Applying the active ingredient to plants" includes: applying the composition of the present invention to plants. As for the composition of the present invention, for example, it can be applied to plants as it is or appropriately diluted, dispersed or dissolved with a liquid such as water, saline, buffer, alcohol, DMSO, etc. That is, the composition of the present invention can be, for example, appropriately adjusted in concentration in a manner to obtain the use concentration of the active ingredient exemplified above, and applied to plants. The composition of the present invention can be applied to plants in particular in the form of a liquid. The composition of the present invention can be used alone or in combination with other ingredients. For other ingredients, the description of ingredients other than the active ingredient in the description of the composition of the present invention can be applied mutatis mutandis. That is, the composition of the present invention can be used in combination with additives such as a spreading agent, for example.

[0262] The application method of the composition of the present invention is not particularly limited as long as the desired effect is obtained. The application method of the composition of the present invention can be appropriately selected according to various conditions such as the type of pests, the type of plants, the cultivation method of plants, the growth and development stage of plants, and the purpose of the use of the composition of the present invention. The composition of the present invention can be applied to plants, for example, by the usual method of applying pesticides or fertilizers to plants. The composition of the present invention can be applied to the plant itself, or to the medium for implementing the cultivation of plants, and can be applied to their combination. In "applying the active ingredient to the plant", it is not limited to applying the composition of the present invention to the plant itself, but also includes applying the composition of the present invention to the medium for implementing the cultivation of plants. The medium for implementing the cultivation of plants is also referred to as "growth and development medium" or "growth and development system." The growth and development medium can be appropriately selected according to various conditions such as the type of plant and the cultivation method of plants. The cultivation method of plants is not particularly limited. As for the cultivation of plants, in addition to applying the composition of the present invention, for example, it can be implemented by the same method as the usual method for cultivating plants. As the cultivation method of plants, soil cultivation, nutrient solution cultivation, and nutrient solution soil cultivation can be cited. As nutrient solution cultivation, hydroponic cultivation and solid culture medium cultivation can be mentioned. As hydroponic cultivation, nutrient film hydroponics (NFT) and deep flow hydroponics (DFT) can be mentioned. That is, as a medium (growth and development medium) for implementing plant cultivation, soil, hydroponic culture solution, and solid culture medium can be mentioned. As an application to the plant itself, spraying, coating, and immersion of the plant can be mentioned. The composition of the present invention can be applied to the whole plant or a part of the plant. For example, in the case where the plant is a plant body, the composition of the present invention can be applied to the whole plant body or a part of the plant body. The composition of the present invention can be applied, for example, to the whole aboveground part of the plant body. As a part of the plant body, leaves, stems, trunks, roots, fruits, and seeds can be mentioned. As a part of the plant body, leaves can be mentioned in particular. When the composition of the present invention is applied to the leaves, the composition of the present invention can be applied only to one side of the surface and back of the leaves, or to both. As the application to the plant body, specifically, for example, foliar spraying and root dipping can be mentioned. As the application to the growth medium, spraying, irrigation and mixing to the growth medium can be mentioned. Specifically, for example, the composition of the present invention can be applied to the growth medium (for example, spraying) through an irrigation pipe. The application to the growth medium can be implemented in a manner that allows the active ingredient to reach a position that can act on the plant. For example, the application to the medium for implementing the cultivation of the plant can be implemented in a manner that allows the active ingredient to reach the rhizosphere of the plant.

[0263] The application period of the composition of the present invention is not particularly limited as long as the desired effect is obtained. As for the application period of the composition of the present invention, it can be appropriately selected according to various conditions such as the type of pests, the type of plants, the cultivation method of plants, the growth and development stage of plants and the purpose of use of the composition of the present invention. When the composition of the present invention is applied to the growth and development medium, the plant may already exist or not exist in the growth and development medium. The desired effect can be obtained in the plant by applying the composition of the present invention to the plant itself, or by applying the composition of the present invention to the growth and development medium where the plant already exists. In addition, the desired effect can be obtained in the plant that may exist in the future growth and development medium by applying the composition of the present invention to the growth and development medium where there is no plant. As the plant that may exist in the future growth and development medium, the plant that will be transferred from the outside to the growth and development medium in the future and the plant generated in the growth and development medium in the future can be cited. The composition of the present invention can be applied only once, twice or more. The composition of the present invention can be applied intermittently or continuously.

[0264] The application amount of the composition of the present invention is not particularly limited as long as the desired effect is obtained. The application amount of the composition of the present invention can be appropriately selected according to various conditions such as the type of pests, the type of plants, the cultivation method of plants, the growth and development stage of plants, the purpose of use of the composition of the present invention, and the application method and application period of the composition of the present invention.

[0265] Regarding the application rate of the composition of the present invention, for example, the application rate of the composition of the present invention in the form of a liquid (for example, the composition of the present invention in the form of a liquid containing the active ingredient at the usage concentration exemplified above) may be 100 L / hectare or more, 200 L / hectare or more, 500 L / hectare or more, 1000 L / hectare or more, 1500 L / hectare or more, 2000 L / hectare or more, 3000 L / hectare or more, 4000 L / hectare or more, 5000 L / hectare or more, 7000 L / hectare or more, 10000 L / hectare or more, 30000 L / hectare or more, 50000 L / hectare or more, 70000 L / hectare or more, 100000 L / hectare or more, 150000 L / hectare or more, 200000 L / hectare or more, 300000 L / hectare or more, 50000 L / hectare or more, 60000 L / hectare or more, 70000 L / hectare or more, L / ha or more, and can be less than 100000 L / ha, less than 750000 L / ha, less than 50000 L / ha, less than 300000 L / ha, less than 200000 L / ha, less than 150000 L / ha, less than 100000 L / ha, less than 70000 L / ha, less than 50000 L / ha, less than 30000 L / ha, less than 10000 L / ha, less than 9000 L / ha, less than 8000 L / ha, less than 7000 L / ha, less than 6000 L / ha, less than 5000 L / ha, less than 4000 L / ha, less than 3000 L / ha, less than 2000 L / ha or less than 1500 L / ha, and can be non-contradictory combinations of these. Regarding the application rate of the composition of the present invention, specifically, for example, the application rate of the composition of the present invention in the form of a liquid (for example, the composition of the present invention in the form of a liquid containing the active ingredient at the usage concentration exemplified above) can be 100 L / hectare to 1500 L / hectare, 1500 L / hectare to 5000 L / hectare, 5000 L / hectare to 10000 L / hectare, 10000 L / hectare to 30000 L / hectare, 30000 L / hectare to 50000 L / hectare, 50000 L / hectare to 100000 L / hectare, 100000 L / hectare to 150000 L / hectare, 150000 L / hectare to 200000 L / hectare, 200000 L / hectare to 500000 L / hectare or 500000 L / hectare to 10000000 L / hectare.Regarding the application rate of the composition of the present invention, specifically, for example, the application rate of the composition of the present invention in liquid form (for example, the composition of the present invention in liquid form containing the active ingredient at the usage concentration exemplified above) can be 100 L / hectare to 1,000,000 L / hectare, 200 L / hectare to 1,000,000 L / hectare, 500 L / hectare to 1,000,000 L / hectare, 1,000 L / hectare to 750,000 L / hectare, 10,000 L / hectare to 750,000 L / hectare or 100,000 L / hectare to 750,000 L / hectare.

[0266] In addition, the application amount of the composition of the present invention can be set not only in consideration of the application area (two-dimensional element) but also in consideration of the three-dimensional element. That is, with respect to the application amount of the composition of the present invention, for example, it can be set according to the height of the plant to which the composition of the present invention is applied (e.g., sprayed). With respect to the application amount of the composition of the present invention, specifically, for example, the application amount of the composition of the present invention in the form of a liquid (e.g., the composition of the present invention in the form of a liquid containing an active ingredient at the use concentration exemplified above) for plants at ground to knee height can be 1000L / hectare to 750000L / hectare, 1000L / hectare to 30000L / hectare, 1000L / hectare to 5000L / hectare, or 1000L / hectare to 1500L / hectare. Regarding the application amount of the composition of the present invention, specifically, for example, the application amount of the composition of the present invention in the form of a liquid (e.g., the composition of the present invention in the form of a liquid containing the active ingredient at the use concentration exemplified above) for plants of knee height to human height can be 1500L / ha to 750,000L / ha, 1500L / ha to 70,000L / ha, 1500L / ha to 10,000L / ha, or 1500L / ha to 3000L / ha. Regarding the application amount of the composition of the present invention, specifically, for example, the application amount of the composition of the present invention in the form of a liquid (e.g., the composition of the present invention in the form of a liquid containing the active ingredient at the use concentration exemplified above) for plants of human height to 2 meters can be 3000L / ha to 750,000L / ha, 3000L / ha to 100,000L / ha, 3000L / ha to 30,000L / ha, or 3000L / ha to 5000L / ha. Regarding the application rate of the composition of the present invention, specifically, for example, the application rate of the composition of the present invention in liquid form (for example, the composition of the present invention in liquid form containing the active ingredient at the usage concentration exemplified above) for plants over 2 meters can be 5000L / hectare to 750000L / hectare, 5000L / hectare to 150000L / hectare, 5000L / hectare to 30000L / hectare or 5000L / hectare to 7000L / hectare.

[0267] When the composition of the present invention is applied (for example, poured into the ground) to a growth medium, the application amount of the composition of the present invention, specifically, for example, the application amount of the composition of the present invention in liquid form (for example, the composition of the present invention in the form of a liquid containing the active ingredient at the usage concentration exemplified above) can be 250,000 L / hectare to 750,000 L / hectare.

[0268] The composition of the present invention may be applied only once or in multiple doses. The composition of the present invention may be applied, for example, in 2 or more doses, 3 or more doses, 5 or more doses, or 10 or more doses. When the composition of the present invention is applied in multiple doses, the "application amount of the composition of the present invention" refers to the total application amount of the composition of the present invention based on multiple doses.

[0269] Furthermore, the dosage of the composition of the present invention can be set, for example, so that the dosage of the active ingredient falls within a given range.

[0270] The amount of the active ingredient applied may be, for example, 1 mmol / hectare or more, 2 mmol / hectare or more, 5 mmol / hectare or more, 10 mmol / hectare or more, 20 mmol / hectare or more, 50 mmol / hectare or more, 100 mmol / hectare or more, 200 mmol / hectare or more, 500 mmol / hectare or more, 1 mol / hectare or more, 2 mol / hectare or more, 5 mol / hectare or more, 10 mol / hectare or more, 20 mol / hectare or more, 50 mol / hectare or more, 100 mol / hectare or more, 200 mol / hectare or more. The amount of iodine per gram of the present invention is preferably 0.5 mol / hectare, 1.0 mol / hectare, 2.0 mol / hectare, 5.0 mol / hectare, 1.0 mol / hectare, 2.0 mol / hectare, 5.0 mol / hectare, 1.0 mol / hectare, 2.0 mol / hectare, 5.0 mol / hectare, 1.0 mol / hectare, 2.0 mol / hectare, 5.0 mol / hectare, 1.0 mol / hectare, 1.0 mol / hectare, 2.0 mol / hectare, 5.0 mol / hectare, 1.0 mol / hectare, 1.0 mol / hectare, 2.0 mol / hectare, 5.0 mol / hectare, 1.0 mol / hectare, 2.0 mol / hectare, 5.0 mol / hectare, 1.0 mol / hectare, 2.0 1 / hectare or less, 20000mol / hectare or less, 10000mol / hectare or less, 5000mol / hectare or less, 2000mol / hectare or less, 1000mol / hectare or less, 500mol / hectare or less, 200mol / hectare or less, 100mol / hectare or less, 50mol / hectare or less, 20mol / hectare or less, 10mol / hectare or less, 5mol / hectare or less, 2mol / hectare or less, 1mol / hectare or less, 500mmol / hectare or less, 200mmol / hectare or less, 100mmol / hectare or less, 50mmol / hectare or less, 20mmol / hectare or less, and these can be non-contradictory combinations.The amount of the active ingredient applied may be, for example, 1 mmol / ha to 2 mmol / ha, 2 mmol / ha to 5 mmol / ha, 5 mmol / ha to 10 mmol / ha, 10 mmol / ha to 20 mmol / ha, 20 mmol / ha to 50 mmol / ha, 50 mmol / ha to 100 mmol / ha, 100 mmol / ha to 200 mmol / ha, 200 mmol / ha to 500 mmol / ha, 500 mmol / ha to 1 mol / ha, 1 mol / ha to 2 mol / ha, 2 mol / ha to 5 mol / ha, 5 mol / ha to 10 mol / ha, 10 mol / ha to 20 mol / ha, 20 mol / ha to 50 mol / ha, 50 mol / ha to 100 mol / ha, 100 mol / ha to 200 mol / ha, 200 mol / ha to 500 mol / ha, 500 mol / ha to 1 1 / ha to 1000 mol / ha, 1000 mol / ha to 2000 mol / ha, 2000 mol / ha to 5000 mol / ha, 5000 mol / ha to 10000 mol / ha, 10000 mol / ha to 20000 mol / ha, 20000 mol / ha to 50000 mol / ha, 50000 mol / ha to 100000 mol / ha, 100000 mol / ha to 150000 mol / ha, 150000 mol / ha to 200000 mol / ha or 200000 mol / ha to 250000 mol / ha. When the composition of the present invention is applied in multiple applications, the "application amount of the active ingredient" refers to the total application amount of the active ingredient based on multiple applications.

[0271] With respect to the description of the mode of application of the composition of the present invention as described above, any other case of applying the active ingredient to a plant can be applied mutatis mutandis. That is, the active ingredient can be applied to a plant, for example, at the concentration used as exemplified above. In addition, the active ingredient can be applied to a plant, for example, at the amount of the active ingredient applied as exemplified above. In addition, the active ingredient can be prepared as a composition such as a liquid composition containing the active ingredient and applied to a plant. For the composition containing the active ingredient, the description of the composition of the present invention can be applied mutatis mutandis. The active ingredient can be applied to a plant in particular in the form of a liquid. That is, with respect to the active ingredient, specifically, for example, it can be prepared as a liquid composition containing the active ingredient at the concentration used as exemplified above and applied to a plant. In addition, the active ingredient can be used in combination with other ingredients such as a spreading agent.

[0272] It should be noted that by cultivating plants using the method of the present invention, plants (specifically, plant bodies) can be obtained. Therefore, one embodiment of the method of the present invention may be a method for producing plants (specifically, plant bodies). More specifically, one embodiment of the method of the present invention may be a method for producing plants (specifically, plant bodies), which comprises: applying an active ingredient (i.e., the ingredient (A)) to a plant to cultivate the plant. As for the cultivation of plants, in addition to applying the active ingredient to the plant, for example, it can be implemented by the same method as the usual method for cultivating plants. The method for cultivating plants is as described above. As for the application of the active ingredient and the cultivation of the plant, for example, it can be implemented in a manner to obtain the desired effect based on the application of the active ingredient. For example, the application of the active ingredient can be implemented during the cultivation of the plant, and the cultivation of the plant can be implemented after the application of the active ingredient is implemented. The application of the active ingredient can be implemented particularly in the cultivation of the plant. Specifically, for example, by applying the active ingredient to the plant and cultivating the plant, an insect pest resistance induction effect, an insect pest control effect, and / or an effect of improving cultivation performance can be obtained, and the plant (specifically, the plant body) can be efficiently manufactured. The plant (specifically the plant body) can be suitably harvested. That is, the method of the present invention can further comprise: harvesting the plant (specifically the plant body). "Harvesting" can be used interchangeably with "recovering". "Harvesting or recovering of a plant" can be used interchangeably with "harvesting or recovering of a plant body". The harvested plant (specifically the plant body) can be the whole plant body or a part of the plant body. Examples of the part of the plant body include leaves, stems, trunks, roots, fruits, and seeds.

[0273] <4> Use of active ingredients

[0274] In addition, the present invention discloses the use of the active ingredients for the above-mentioned purposes. That is, the present invention discloses, for example, the use of the active ingredients for inducing plant resistance to pests, controlling plant pests and / or improving plant cultivation performance, and the use of the active ingredients in the preparation of a composition for inducing plant resistance to pests, controlling plant pests and / or improving plant cultivation performance.

[0275] In addition, the present invention discloses active ingredients for the above-mentioned uses. That is, the present invention discloses, for example, active ingredients for inducing plant resistance to pests, controlling plant pests, and / or improving plant cultivation performance; and active ingredients for the preparation of compositions for inducing plant resistance to pests, controlling plant pests, and / or improving plant cultivation performance.

[0276] [Example]

[0277] Hereinafter, the present invention will be further specifically described by way of non-limiting examples.

[0278] (synthesis example)

[0279] Compounds 1 to 58 and 67 to 75 were obtained by the following method. The structures of Compounds 1 to 58 and 67 to 75 are represented by the following formulae (Compound 1) to (Compound 58) and (Compound 67) to (Compound 75), respectively.

[0280] (Synthesis Example 1) Synthesis of Compound 1

[0281] (Step 1) Synthesis of Compound 1 Intermediate

[0282] To an acetonitrile solution (5 mL) of N-Cbz-glutamic acid-α-benzyl ester (361 mg, 0.97 mmol) was added HOAt (135 mg, 0.99 mmol) and WSC·HCl (191 mg, 1.00 mmol), and the mixture was stirred at room temperature for 1 hour. Isopropanol (0.5 mL) and triethylamine (0.05 mL, 0.36 mmol) were added to the reaction solution, and the mixture was further stirred at room temperature for 18 hours. Ethyl acetate was added to the reaction solution, and the mixture was washed with 10% aqueous citric acid solution and saturated aqueous sodium bicarbonate solution in sequence. The organic layer was dehydrated and dried with anhydrous sodium sulfate, and then concentrated, dried and solidified under reduced pressure to obtain the intermediate of compound 1.

[0283] Yield 80%; ESI MS m / z 414.1 (M+H) + ; 1 H NMR(400MHz,CD3OD)d 7.38-7.32(10H,m),5.21(1H,d,J=12.4Hz),5.16(1H,d,J=12.4Hz),5.10(2H,s),4.96(1H,m),4 .30(1H,dd,J=4.8,9.2Hz),2.40-2.36(2H,m),2.17(1H,m),1.95(6H,m),1.22(6H,d,J=6.4Hz).

[0284] [Chemical formula 10]

[0285]

[0286] (Step 2) Synthesis of Compound 1

[0287] After adding ethyl acetate (10 mL), water (10 mL) and acetic acid (0.1 mL) to the intermediate of compound 1 (319 mg, 0.77 mmol), 5% palladium carbon (43 mg) was added, and stirred at room temperature for 20 hours under a hydrogen atmosphere. The reaction solution was filtered, and the aqueous layer was concentrated and dried under reduced pressure to solidify to obtain compound 1.

[0288] Yield 96%; ESI MS m / z 190.0 (M+H) + ; 1 H NMR (400MHz, D2O) d4.92 (1H, m), 3.69 (1H, t, J = 6.4Hz), 2.47-2.42 (2H, m), 2.10-2.03 (2H, m), 1.16 (6H, t, J = 6.4Hz).

[0289] [Chemical formula 11]

[0290]

[0291] (Synthesis Example 2) Synthesis of Compound 2

[0292] (Step 1) Synthesis of Compound 2 Intermediate

[0293] Using N-Cbz-glutamic acid-α-benzyl ester and isobutyl alcohol as raw materials, the intermediate of compound 2 was obtained by the same method as that for preparing the intermediate of compound 1.

[0294] Yield 89%; ESI MS m / z 428.2 (M+H) + ; 1 H NMR(400MHz,CD3OD)d 7.38-7.30(10H,m),5.21(1H,d,J=12.0Hz),5.16(1H,d,J=12.0Hz),5.12(1H,d,J=12.4Hz),5.09(1H,d,J=12.4Hz),4.31 (1H,dd,J=5.2,9.6Hz),3.86(2H,d,J=6.8Hz),2.46-2.42(2H,m),2.20(1H,m),1.96-1.89(2H,m),0.93(6H,d,J=6.8Hz).

[0295] [Chemical formula 12]

[0296]

[0297] (Step 2) Synthesis of Compound 2

[0298] Compound 2 was obtained by the same method as that for preparing Compound 1 using the intermediate of Compound 2 as a raw material.

[0299] Yield 85%; ESI MS m / z 204.1 (M+H) + ; 1H NMR (400MHz, D2O) d3.85 (2H, d, J = 6.4Hz), 3.71 (1H, t, J = 6.4Hz), 2.53-2.49 (2H, m), 2.12-2.06 (2H, m), 1.87 (1H, m), 0.84 (6H, d, J = 6.8Hz).

[0300] [Chemical formula 13]

[0301]

[0302] (Synthesis Example 3) Synthesis of Compound 3

[0303] (Step 1) Synthesis of Compound 3 Intermediate

[0304] Using N-Cbz-glutamic acid-α-benzyl ester and cyclopropanol as raw materials, the intermediate compound 3 was obtained by the same method as that for the intermediate compound 1.

[0305] Yield 78%; ESI MS m / z 412.1 (M+H) + ; 1 H NMR(400MHz,CD3OD)d 7.38-7.30(10H,m),5.21(1H,d,J=12.8Hz),5.16(1H,d,J=12.8Hz),5.11(2H,s),4.29(1H,dd ,J=4.8,9.2Hz),4.08(1H,m),2.41-2.37(2H,m),2.17(1H,m),1.94(1H,m),0.70-0.64(4H,m).

[0306] [Chemical formula 14]

[0307]

[0308] (Step 2) Synthesis of Compound 3

[0309] Compound 3 was obtained by the same method as that for preparing Compound 1 using the intermediate of Compound 3 as a raw material.

[0310] Yield 56%; ESI MS m / z 188.1 (M+H) + ; 1 H NMR(400MHz,D2O)d3.98(1H,m),3.67(1H,t,J=6.4Hz),2.50-2.41(2H,m),2.08-2.02(2H,m),0.66-0.65(4H,m).

[0311] [Chemical formula 15]

[0312]

[0313] (Synthesis Example 4) Synthesis of Compound 4

[0314] (Step 1) Synthesis of Compound 4 Intermediate

[0315] Using N-Cbz-glutamic acid-α-benzyl ester and 3-pentanol as raw materials, the intermediate compound 4 was obtained by the same method as that for the intermediate compound 1.

[0316] Yield 95%; ESI MS m / z 442.2 (M+H) + ; 1 H NMR(400MHz,CD3OD)d 7.36-7.30(10H,m),5.21-5.09(4H,m),4.74(1H,m),4.33(1H,dd,J=5.2,9.2Hz),2. 44-2.40(2H,m),2.18(1H,m),1.95(1H,m),1.58-1.50(4H,m),0.86(6H,t,J=7.6Hz).

[0317] [Chemical formula 16]

[0318]

[0319] (Step 2) Synthesis of Compound 4

[0320] Compound 4 was obtained by the same method as that for preparing Compound 1, using the intermediate of Compound 4 as a raw material.

[0321] Yield 89%; ESI MS m / z 218.1 (M+H) + ; 1 H NMR(400MHz,D2O)d3.69(1H,t,J=6.4Hz),2.53-2.48(2H,m),2.11-2.04(2H,m),1.58-1.44(4H,m),0.77(6H,t,J=7.6Hz).

[0322] [Chemical formula 17]

[0323]

[0324] (Synthesis Example 5) Synthesis of Compound 5

[0325] (Step 1) Synthesis of Compound 5 Intermediate

[0326] Using N-Cbz-glutamic acid-α-benzyl ester and cyclobutanol as raw materials, the intermediate compound 5 was obtained by the same method as that for the intermediate compound 1.

[0327] Yield 95%; ESI MS m / z 426.2 (M+H) + ; 1 H NMR(400MHz,CD3OD)d 7.37-7.30(10H,m),5.19(1H,d,J=12.4Hz),5.15(1H,d,J=12.4Hz),5.10(2H,s),4.30(1H,dd,J=5.2,9 .2Hz),2.40-2.36(2H,m),2.33-2.27(2H,m),2.16(1H,m),2.09-1.88(3H,m),1.77(1H,m),1.63(1H,m).

[0328] [Chemical formula 18]

[0329]

[0330] (Step 2) Synthesis of Compound 5

[0331] Compound 5 was obtained by the same method as that for preparing Compound 1 using the intermediate of Compound 5 as a raw material.

[0332] Yield 55%; ESI MS m / z 202.1 (M+H) + ; 1 H NMR(400MHz,D2O)d4.87(1H,m),3.67(1H,t,J=6.4Hz),2.47-2.43(2H,m),2.24-2.20(2H,m),2.08-1.98(4H,m),1.71(1H,m),1.54(1H,m).

[0333] [Chemical formula 19]

[0334]

[0335] (Synthesis Example 6) Synthesis of Compound 6

[0336] (Step 1) Synthesis of Compound 6 Intermediate

[0337] Using N-Boc-glutamic acid-α-tert-butyl ester and isopropylamine as raw materials, the intermediate compound 6 was obtained by the same method as that for the intermediate compound 1.

[0338] Yield 88%; ESI MS m / z 345.2 (M+H) + ;1 H NMR(400MHz,CD3OD)d 3.88-3.82(2H,m),2.13(2H,t,J=7.6Hz),1.94(1H,m),1.76(1H,m),1.37(9H,s),1.34(9H,s),1.03(3H,d,J=6.4Hz),1.02(3H,d,J=6.4Hz).

[0339] [Chemical formula 20]

[0340]

[0341] (Step 2) Synthesis of Compound 6

[0342] The intermediate of compound 6 (94 mg, 0.27 mmol) was dissolved in a 4N hydrochloric acid dioxane solution (2 mL), and stirred at room temperature for 18 hours. The reaction solution was concentrated to dryness and solidified under reduced pressure to obtain the hydrochloride of compound 6.

[0343] Yield 99%; ESI MS m / z 189.1 (M+H) + ; 1 H NMR (400MHz, D2O) d3.99 (1H, t, J = 6.4Hz), 3.82 (1H, dd, J = 6.8, 9.2Hz), 2.73-2.32 (2H, m), 2.15-2.09 (2H, m), 1.03 (6H, d, J = 6.8Hz).

[0344] [Chemical formula 21]

[0345]

[0346] (Synthesis Example 7) Synthesis of Compound 7

[0347] (Step 1) Synthesis of Intermediate of Compound 7

[0348] Using N-Boc-glutamic acid-α-tert-butyl ester and cyclopropylamine as raw materials, the intermediate compound 7 was obtained by the same method as that for the intermediate compound 1.

[0349] Yield 72%; ESI MS m / z 343.2 (M+H) + ; 1H NMR(400MHz,CD3OD)d 3.85(1H,m),2.53(1H,m),2.12(2H,t,J=7.6Hz),1.96(1H,m),1.73(1H,m),1.37(9H,s),1.34(9H,s),0.61-0.59(2H,m),0.38-0.36(2H,m).

[0350] [Chemical formula 22]

[0351]

[0352] (Step 2) Synthesis of Compound 7

[0353] The hydrochloride of Compound 7 was obtained by the same method as that of Compound 6 using the intermediate of Compound 7 as a raw material.

[0354] Yield 99%; ESI MS m / z 187.0 (M+H) + ; 1 H NMR(400MHz,D2O)d3.80(1H,t,J=6.4Hz),2.27(1H,m),2.16-2.11(2H,m),1.94-1.87(2H,m),0.44-0.41(2H,m),0.23-0.20(2H,m).

[0355] [Chemical formula 23]

[0356]

[0357] (Synthesis Example 8) Synthesis of Compound 8

[0358] (Step 1) Synthesis of the intermediate of compound 8

[0359] Using N-Boc-glutamic acid-α-tert-butyl ester and dimethylamine hydrochloride as raw materials, the intermediate of compound 8 was obtained by the same method as that of the intermediate of compound 1.

[0360] Yield 92%; ESI MS m / z 331.2 (M+H) + ; 1 H NMR (400MHz, CD3OD)d 4.02(1H,m),3.07(3H,s),2.95(3H,s),2.51-2.45(2H,m),2.10(1H,m),1.89(1H,m),1.49(9H,s),1.46(9H,s).

[0361] [Chemical formula 24]

[0362]

[0363] (Step 2) Synthesis of Compound 8 (known)

[0364] The hydrochloride of Compound 8 was obtained by the same method as that of Compound 6 using the intermediate of Compound 8 as a raw material.

[0365] Yield 99%; ESI MS m / z 175.1 (M+H) + ; 1 H NMR(400MHz,D2O)d 4.02(1H,t,J=6.4Hz),2.93(3H,s),2.80(3H,s),2.56-2.52(2H,m),2.14-2.05(2H,m).

[0366] [Chemical formula 25]

[0367]

[0368] (Synthesis Example 9) Synthesis of Compound 9

[0369] (Step 1) Synthesis of Compound 9 Intermediate

[0370] Using N-Cbz-glutamic acid-α-benzyl ester and n-propanol as raw materials, the intermediate of compound 9 was obtained by the same method as that of the intermediate of compound 1.

[0371] Yield 93%; ESI MS m / z 414.1 (M+H)+; 1H NMR (400 MHz, CD3OD) d 7.38-7.30 (10H, m), 5.20 (1H, d, J=12.4 Hz), 5.16 (1H, d, J=12.4 Hz), 5.10 (2H, s), 4.31 (1H, dd, J=5.2, 9.2 Hz), 4.02 (2H, t, J=6.8 Hz), 2.44-2.40 (2H, m), 2.18 (1H, m), 1.96 (1H, m), 1.68-1.59 (2H, m), 0.94 (3H, t, J=7.2 Hz).

[0372] [Chemical formula 26]

[0373]

[0374] (Step 2) Synthesis of Compound 9

[0375] Compound 9 was obtained by the same method as that for preparing Compound 1 using the intermediate of Compound 9 as a raw material.

[0376] Yield 88%; ESI MS m / z 190.1 (M+H) + ; 1 H NMR(400MHz,D2O)d3.99(2H,t,J=6.8Hz),3.66(1H,t,J=6.4Hz),2.50-2.45(2H,m),2.09-2.02(2H,m),1.59-1.54(2H,m),0.82(3H,t,J=7.2Hz).

[0377] [Chemical formula 27]

[0378]

[0379] (Synthesis Example 10) Synthesis of Compound 10

[0380] (Step 1) Synthesis of Intermediate of Compound 10

[0381] Using N-Cbz-glutamic acid-α-benzyl ester and ethanolamine as raw materials, the intermediate compound 10 was obtained by the same method as that for the intermediate compound 1.

[0382] Yield 92%; ESI MS m / z 415.1 (M+H) + ; 1 H NMR(400MHz,CD3OD)d 7.37-7.30(10H,m),5.20-5.06(4H,m),4.27(1H,dd,J=4.8,9.6Hz),3.58(2H,t ,J=5.6Hz),3.30-3.25(2H,m),2.32(2H,t,J=7.6Hz),2.20(1H,m),1.95(1H,m).

[0383] [Chemical formula 28]

[0384]

[0385] (Step 2) Synthesis of Compound 10

[0386] Compound 10 was obtained by the same method as that for preparing Compound 1, using the intermediate of Compound 10 as a raw material.

[0387] Yield 83%; ESI MS m / z 191.0 (M+H) + ; 1H NMR (400MHz, D2O)d 3.67(1H,t,J=6.4Hz), 3.56(2H,t,J=5.6Hz), 3.24(2H,t,J=5.6Hz), 2.37-2.30(2H,m), 2.07-2.02(2H,m).

[0388] [Chemical formula 29]

[0389]

[0390] (Synthesis Example 11) Synthesis of Compound 11

[0391] (Step 1) Synthesis of Intermediate of Compound 11

[0392] To N α -Boc-2,4-diaminobutyric acid-tert-butyl ester hydrochloride (311mg, 1.00mmol) in acetonitrile solution (4mL), under ice-cold conditions, triethylamine (0.4mL, 2.87mmol) was added and stirred for 5 minutes. Methanesulfonyl chloride (0.075mL, 0.97mmol) was added to the reaction solution and further stirred for 1 hour at the same temperature. After adding ethyl acetate to the reaction solution, it was distributed and washed with 0.1N hydrochloric acid. After dehydrating and drying the organic layer with anhydrous sodium sulfate, the intermediate of compound 11 was obtained by concentrating, drying and solidifying under reduced pressure.

[0393] Yield 90%; ESI MS m / z 375.1 (M+Na) + ; 1 H NMR (400MHz, CD3OD)d 4.10(1H,dd,J=4.8,9.2Hz),3.21-3.09(2H,m),2.95(3H,s),2.03(1H,m),1.84(1H,m),1.49(9H,s),1.47(9H,s).

[0394] [Chemical formula 30]

[0395]

[0396] (Step 2) Synthesis of Compound 11

[0397] The intermediate of compound 11 (310 mg, 0.88 mmol) was dissolved in 4N hydrochloric acid in dioxane (2 mL), and stirred at room temperature for 18 hours. The solution was concentrated to dryness and solidified under reduced pressure to obtain the hydrochloride of compound 11.

[0398] Yield 99%; ESI MS m / z 197.0 (M+H) + ; 1H NMR (400MHz, D2O) d4.09 (1H, t, J = 6.4Hz), 3.22 (2H, t, J = 6.8Hz), 2.97 (3H, s), 2.14 (1H, m), 2.04 (1H, m).

[0399] [Chemical formula 31]

[0400]

[0401] (Synthesis Example 12) Synthesis of Compound 12

[0402] (Step 1) Synthesis of the intermediate of compound 12

[0403] N α Using -Boc-ornithine-tert-butyl ester and methanesulfonyl chloride as raw materials, the intermediate compound 12 was obtained by the same method as that for the intermediate compound 11.

[0404] Yield 89%; ESI MS m / z 389.1 (M+Na) + ; 1 H NMR (400MHz, CD3OD) d 3.99 (1H, dd, J = 4.8, 8.0Hz), 3.09 (2H, t, J = 6.4Hz), 2.95 (3H, s), 1.85 (1H, m), 1.70-1.61 (3H, m), 1.49 (9H, s), 1.47 (9H, s).

[0405] [Chemical formula 32]

[0406]

[0407] (Step 2) Synthesis of Compound 12

[0408] The hydrochloride of Compound 12 was obtained by the same method as that of Compound 11 using the intermediate of Compound 12 as a raw material.

[0409] Yield 99%; ESI MS m / z 211.0 (M+H) + ; 1 H NMR (400MHz, D2O) d4.02 (1H, t, J = 6.4Hz), 3.05 (2H, t, J = 6.8Hz), 2.96 (3H, s), 1.96-1.85 (2H, m), 1.66-1.52 (2H, m).

[0410] [Chemical formula 33]

[0411]

[0412] (Synthesis Example 13) Synthesis of Compound 13

[0413] (Step 1) Synthesis of Intermediate of Compound 13

[0414] Using N-Cbz-serine tert-butyl ester and isovaleric acid as raw materials, the intermediate compound 13 was obtained by the same method as that for the intermediate compound 1.

[0415] Yield 55%; ESI MS m / z 402.2 (M+Na) + ; 1 H NMR(400MHz,CD3OD)d 7.40-7.31(5H,m),5.14(1H,d,J=12.8Hz),5.11(1H,d,J=12.8Hz),4.42(1H,t,J=4.8Hz),4.36(2H, d,J=4.8Hz),2.21(2H,d,J=7.2Hz),2.05(1H,m),1.48(6H,s),1.43(3H,brs),0.95(6H,d,J=6.8Hz).

[0416] [Chemical formula 34]

[0417]

[0418] (Step 2) Synthesis of Compound 13

[0419] The intermediate of compound 13 (205 mg, 0.54 mmol) was dissolved in 4N hydrochloric acid dioxane (3 mL) and stirred at room temperature for 18 hours. The residue obtained by concentrating, drying and solidifying under reduced pressure was dissolved in ethyl acetate / water (1: 1) (20 mL), 5% palladium carbon (32 mg) was added, and stirred at room temperature for 18 hours under a hydrogen atmosphere. After filtering the reaction solution, the water layer of the filtrate was concentrated, dried and solidified under reduced pressure to obtain compound 13.

[0420] Yield 46%; ESI MS m / z 190.1 (M+H) + ; 1 H NMR(400MHz,D2O)d4.42(1H,dd,J=4.0,5.2Hz),3.87(1H,dd,J=5.2,12.0Hz),3.80(1H,dd,J=4 .0,12.0Hz), 2.12(2H,d,J=6.8Hz), 1.94(1H,m), 0.86(3H,d,J=6.8Hz), 0.85(3H,d,J=6.8Hz).

[0421] [Chemical formula 35]

[0422]

[0423] (Synthesis Example 14) Synthesis of Compound 14

[0424] (Step 1) Synthesis of Intermediate of Compound 14

[0425] Using N-Cbz-serine tert-butyl ester and 3-hydroxybutyric acid as raw materials, the intermediate compound 14 was obtained by the same method as that for the intermediate compound 1.

[0426] Yield 40%; ESI MS m / z 404.1 (M+Na) + ; 1 H NMR(400MHz,CD3OD)d 7.40-7.31(5H,m),5.13(2H,s),4.44-4.35(2H,m),4.16(1H,dd,J=6.4,12 .8Hz),2.46-2.44(2H,m),1.48(6H,s),1.43(3H,brs),1.22-1.20(3H,m).

[0427] [Chemical formula 36]

[0428]

[0429] (Step 2) Synthesis of Compound 14

[0430] Compound 14 was obtained by the same method as that for preparing Compound 13 using the intermediate of Compound 14 as a raw material.

[0431] Yield 57%; ESI MS m / z 192.0 (M+H) + ; 1 H NMR(400MHz,D2O)d4.52-4.43(2H,m),4.17(1H,m),4.05(1H,dd,J=3.2,4.4Hz),2.59-2.43(2H,m),1.15(6H,d,J=6.4Hz).

[0432] [Chemical formula 37]

[0433]

[0434] (Synthesis Example 15) Synthesis of Compound 15

[0435] (Step 1) Synthesis of Intermediate of Compound 15

[0436] To a THF solution (2mL) of N-Cbz-serine benzyl ester (331mg, 1.01mmol), triethylamine (0.2mL, 1.43mmol) was added under ice-cold conditions, followed by isopropyl chloroformate (0.15mL, 1.31mmol), and stirred at the same temperature for 0.5 hours. After adding ethyl acetate to the reaction solution, it was distributed and cleaned with 0.1N hydrochloric acid. After the organic layer was dehydrated and dried with anhydrous sodium sulfate, it was concentrated, dried and solidified by decompression. The residue was purified by reverse phase HPLC (water-acetonitrile), thereby obtaining the intermediate of compound 15.

[0437] Yield 53%; ESI MS m / z 416.1 (M+H) + ; 1 H NMR(400MHz,CD3OD)d 7.38-7.30(10H,m),5.23(1H,d,J=12.4Hz),5.18(1H,d,J=12.4Hz),5.12(2H,s),4.81(1H,m ), 4.62 (1H, t, J = 5.2Hz), 4.44 (2H, d, J = 5.2Hz), 1.26 (3H, d, J = 6.4Hz), 1.25 (3H, d, J = 6.0Hz).

[0438] [Chemical formula 38]

[0439]

[0440] (Step 2) Synthesis of Compound 15

[0441] Compound 15 was obtained by the same method as that for preparing Compound 2 using the intermediate of Compound 15 as a raw material.

[0442] Yield 50%; ESI MS m / z 192.0 (M+H) + ; 1 H NMR (400MHz, D2O) d4.81 (1H, m), 4.49-4.43 (2H, m), 3.98 (1H, dd, J = 4.0, 4.8Hz), 1.21 (6H, d, J = 6.4Hz).

[0443] [Chemical formula 39]

[0444]

[0445] (Synthesis Example 16) Synthesis of Compound 67

[0446] (Step 1) Synthesis of Intermediate 1 of Compound 67

[0447] Compound 67 intermediate 1 was synthesized using Cbz-glutamic acid α-tert-butyl ester and valine tert-butyl ester as raw materials by the same method as compound 1 intermediate.

[0448] Yield 98%; ESI MS m / z 493.3 (M+H) + ; 1 H NMR (400MHz, CD3OD) δ7.40-7.31(5H,m),5.13(1H,d,J=12.4Hz),5.09(1H,d,J=12.4Hz),4.21(1H,d,J=5.6Hz),4.09(1H,dd,J=4.4,10 .0Hz),2.40(2H,t,J=7.6Hz),2.18-2.10(2H,m),1.90(1H,m),1.48(9H,s),1.47(9H,s),0.87(3H,d,J=6.8Hz),0.86(3H,d,J=6.8Hz).

[0449] [Chemical formula 40]

[0450]

[0451] (Step 2) Synthesis of Intermediate 2 of Compound 67

[0452] Using compound 67 intermediate 1 as a starting material, compound 67 intermediate 2 was obtained by the same method as compound 1.

[0453] Yield 98%; ESI MS m / z 359.2M+H) + ; 1 H NMR(400MHz,CD3OD)δ4.21(1H,d,J=5.6Hz),3.37(1H,dd,J=5.2,7.2Hz),2.41-2.37(2H,m ),2.14(1H,m),2.03(1H,m),1.85(1H,m),1.50(9H,s),1.49(9H,s),0.98(6H,d,J=6.8Hz).

[0454] [Chemical formula 41]

[0455]

[0456] (Step 3) Synthesis of Intermediate 3 of Compound 67

[0457] Using Boc-glutamic acid α-tert-butyl ester and compound 67 intermediate 2 as raw materials, compound 67 intermediate 3 was obtained by the same method as compound 1 intermediate.

[0458] Yield 90%; ESI MS m / z 644.5 (M+H) + ; 1 H NMR(400MHz,CD3OD)δ4.30-4.20(2H,m),4.01(1H,m),2.40-2.35(4H,m),2.21-2.12(4H,m) ,1.86(1H,m),1.488(18H,s),1.485(18H,s),0.99(3H,d,J=6.8Hz),0.98(3H,d,J=6.8Hz).

[0459] [Chemical formula 42]

[0460]

[0461] (Step 4) Synthesis of Compound 67

[0462] Compound 67 was obtained by the same method as compound 11 using intermediate 3 of compound 67 as a starting material.

[0463] Yield 99%; ESI MS m / z 376.1 (M+H) + ; 1 H NMR (400MHz, D2O) δ4.25 (1H, dd, J = 4.8, 9.2Hz), 4.16 (1H, d, J = 6.0Hz), 4.01 (1H, t, J = 6.4Hz), 2.50-2.46 (2H,m),2.39-2.35(2H,m),2.17-2.06(4H,m),1.92(1H,m),0.86(3H,d,J=6.8Hz),0.85(3H,d,J=6.8Hz).

[0464] [Chemical formula 43]

[0465]

[0466] (Synthesis Example 17) Synthesis of Compound 68

[0467] (Step 1) Synthesis of Intermediate 1 of Compound 68

[0468] Using Cbz-valine and valine tert-butyl ester as raw materials, compound 68 intermediate 1 was obtained by the same method as compound 1 intermediate.

[0469] Yield 96%; ESI MS m / z 429.2 (M+Na) + ; 1H NMR (400MHz, CD3OD) δ7.38-7.29(5H,m),5.11(2H,s),4.24(1H,d,J=6.0Hz),4.05(1H,d,J=7.2Hz),2.16-2.03(2H,m),1.00-0.96(12H,m).

[0470] [Chemical formula 44]

[0471]

[0472] (Step 2) Synthesis of Intermediate 2 of Compound 68

[0473] Using compound 68 intermediate 1 as a starting material, compound 68 intermediate 2 was obtained by the same method as compound 1.

[0474] Yield 93%; ESI MS m / z 273.1 (M+H) + ; 1 H NMR (400MHz, CD3OD) δ4.22(1H,d,J=5.6Hz), 3.22(1H,d,J=5.2Hz), 2.15(1H,m), 2.01(1H,m), 1.49(9H,s), 1.02-0.93(12H,m).

[0475] [Chemical formula 45]

[0476]

[0477] (Step 3) Synthesis of Intermediate 3 of Compound 68

[0478] Using Boc-glutamic acid α-tert-butyl ester and compound 68 intermediate 2 as raw materials, compound 68 intermediate 3 was obtained by the same method as compound 1.

[0479] Yield 90%; ESI MS m / z 558.5 (M+H) + ; 1 H NMR(400MHz,CD3OD)δ4.25-4.19(2H,m),3.99(1H,dd,J=4.8,9.6Hz),2.39-2.35(2H ,m),2.16-2.05(2H,m),1.85(1H,m),1.49(18H,s),1.46(9H,s),1.01-0.96(12H,m).

[0480] [Chemical formula 46]

[0481]

[0482] (Step 4) Synthesis of Compound 68

[0483] Compound 68 was obtained by using intermediate 3 of compound 68 as a starting material in the same manner as compound 11.

[0484] Yield 99%; ESI MS m / z 346.1 (M+H) + ; 1 H NMR (400MHz, D2O) δ4.17 (1H, d, J = 6.4Hz), 4.04 (1H, d, J = 7.6Hz), 3.96 (1H, t, J = 6.4Hz), 2.51 -2.44(2H,m),2.14-2.09(2H,m),1.97(1H,m),0.88(3H,d,J=6.8Hz),0.87(3H,d,J=6.4Hz).

[0485] [Chemical formula 47]

[0486]

[0487] (Other) Acquisition of Compounds 16 to 58 and 69 to 75

[0488] The following compounds 16 to 58 and 69 to 75 were suitably obtained by purchasing or the like.

[0489] That is, compounds 16, 21, 22, 23, 25, 28, 30, 32, 33, 34, 54 and 56 were purchased from BACHEM. In addition, compounds 38, 46 and 52 were purchased from SIGMA. In addition, compounds 44 and 45 were purchased from the Peptide Institute. In addition, compounds 17, 27, 31 and 48 were purchased from Domestic Chemicals. In addition, compound 51 was purchased from Watanabe Chemicals. In addition, compounds 18, 19, 35, 37, 41, 42, 43, 47, 49, 50, 53, 55, 57 and 58 were purchased from Tokyo Chemical Industry. In addition, compound 36 was purchased from Fujifilm Wako Pure Chemical Industries. In addition, compound 70 was purchased from NACALAITESQUE. In addition, compounds 71 ​​to 75 were obtained by commissioned synthesis by Watanabe Chemicals.

[0490] [Chemical formula 48]

[0491]

[0492] [Chemical formula 49]

[0493]

[0494] [Chemical formula 50]

[0495]

[0496] [Chemical formula 51]

[0497]

[0498] [Chemical formula 52]

[0499]

[0500] [Chemical formula 53]

[0501]

[0502] [Chemical formula 54]

[0503]

[0504] [Chemical formula 55]

[0505]

[0506] [Chemical formula 56]

[0507]

[0508] [Chemical formula 57]

[0509]

[0510] [Chemical formula 58]

[0511]

[0512] [Chemical formula 59]

[0513]

[0514] [Chemical formula 60]

[0515]

[0516] [Chemical formula 61]

[0517]

[0518] [Chemical formula 62]

[0519]

[0520] [Chemical formula 63]

[0521]

[0522] [Chemical formula 64]

[0523]

[0524] [Chemical formula 65]

[0525]

[0526] [Chemical formula 66]

[0527]

[0528] [Chemical formula 67]

[0529]

[0530] [Chemical formula 68]

[0531]

[0532] [Chemical formula 69]

[0533]

[0534] [Chemical formula 70]

[0535]

[0536] [Chemical formula 71]

[0537]

[0538] [Chemical formula 72]

[0539]

[0540] [Chemical formula 73]

[0541]

[0542] [Chemical formula 74]

[0543]

[0544] [Chemical formula 75]

[0545]

[0546] [Chemical formula 76]

[0547]

[0548] [Chemical formula 77]

[0549]

[0550] [Chemical formula 78]

[0551]

[0552] [Chemical formula 79]

[0553]

[0554] [Chemical formula 80]

[0555]

[0556] [Chemical formula 81]

[0557]

[0558] [Chemical formula 82]

[0559]

[0560] [Chemical formula 83]

[0561]

[0562] [Chemical formula 84]

[0563]

[0564] [Chemical formula 85]

[0565]

[0566] [Chemical formula 86]

[0567]

[0568] [Chemical formula 87]

[0569]

[0570] [Chemical formula 88]

[0571]

[0572] [Chemical formula 89]

[0573]

[0574] [Chemical formula 90]

[0575]

[0576] [Chemical formula 91]

[0577]

[0578] [Chemical formula 92]

[0579]

[0580] [Chemical formula 93]

[0581]

[0582] [Chemical formula 94]

[0583]

[0584] [Chemical formula 95]

[0585]

[0586] [Chemical formula 96]

[0587]

[0588] [Chemical formula 97]

[0589]

[0590] [Example 1] Arabidopsis Ca2+ of various compounds 2+ Evaluation of signal-inducing activity

[0591] In this embodiment, Ca 2+ The real-time imaging assay visualized by fluorescence was used to investigate the Ca2+ production by the contact of compounds 1-58 and 67-75 with the glutamate receptors of Arabidopsis thaliana. 2+ Specifically, the recombinant Arabidopsis thaliana p35S::GCaMP3 into which a gene encoding the calcium-sensitive fluorescent protein GCaMP3 was introduced was used as a material to analyze the intracellular Ca signal when treated with compounds 1 to 58 and 67 to 75. 2+ The concentration changes are detected and used as the fluorescence brightness of GCaMP3 to monitor the Ca2+ in the plant in real time. 2+ Signal transduction was analyzed.

[0592] Ca 2+ The real-time imaging experiment of the signal was carried out in the following manner.

[0593] As plant materials, 2-week-old Arabidopsis thaliana recombinant p35S::GCaMP3 cultured on sterile agar medium [1×MS salt, 1% (w / v) sucrose, 0.01% (w / v) inositol, 0.05% (w / v) MES and 0.4% (w / v) gellan gum; pH adjusted to 5.8 with KOH] was used. A small incision of about 1 mm was cut at the tip of the first leaf with scissors and left to stand for 35 minutes. Next, the plant body was placed on a fluorescence microscope SMZ25 (NIKON SOLUTIONS), and 3 μL of the compound solution was applied to the cut of the leaf, and the generated Ca was detected by ORCA-Flash4.0 V2 (HAMAMATSU PHOTONICS). 2+ The signal was displayed and observed in real time. For the compound solution, the following solutions were used: Compounds 1 to 58 and 67 to 75, negative controls, and positive controls were prepared as 100 mM solutions using dilution media [1×MS salt, 1% (w / v) sucrose, 0.01% (w / v) inositol, and 0.05% (w / v) MES; pH adjusted to 5.8 with KOH]. Some compounds with lower solubility were prepared as 10 mM solutions and used as compound solutions. A solution that does not generate Ca was used as a negative control. 2+ Sorbitol was used as a positive control. Glutamate was used as a positive control. 2+ Compounds that induce Ca signaling 2+ Signaling compounds.

[0594] The results showed that compounds 1 to 58 and 67 to 75 all showed Ca 2+ signal, i.e., its induction of Ca 2+ In particular, strong Ca signals were confirmed in compounds 1 and 34. 2+ Signal induction.

[0595] [Example 2] Evaluation of the expression-inducing activity of various compounds on insect pest resistance genes

[0596] In this example, the strong Ca 2+ Compounds 1 and 34 with signal-inducing activity were analyzed by qPCR to determine whether they induced the expression of insect resistance genes in plants.

[0597] As the insect pest resistance gene, the AtOPR3 (12-oxo phytodienoate reductase; involved in jasmonic acid biosynthesis) gene, which is a representative insect pest resistance gene, was selected. As an internal standard, the AtACT8 gene was selected. In the plant material, the Arabidopsis recombinant p35S::GCaMP3 was used, and the first leaf incision formation and compound treatment were performed on the cultivated plant body in the same manner as in Example 1. As compounds, compounds 1 and 34 were used. The sixth leaf after 0 minutes and 30 minutes of compound treatment was recovered and frozen with liquid nitrogen. Total RNA (total RNA) was extracted from frozen leaf samples (50-200 mg) using RNeasy Plant Mini Kit (Qiagen) and according to the instructions. The total RNA obtained was removed based on RNase free DNase I according to the instructions. The total RNA sample was used and single-stranded cDNA was prepared by SuperScriptIII First-Strand Synthesis System for RT-PCR (Invitrogen). cDNA equivalent to 10 ng of total RNA was used as a template, the primer concentration was 200 nM, and the reaction system was prepared into 15 μL using 2×Eva Green qPCR master mix. qPCR was performed using Mx3000P QPCRSystem and MxPro qPCR software (Agilent Technologies) at 95°C for 15 minutes, 40 cycles of 95°C for 20 seconds, 58°C for 15 seconds, 65°C for 15 seconds. Primers of SEQ ID NO.1 and 2 were used in the qPCR of the AtOPR3 gene. Primers of SEQ ID NO.3 and 4 were used in the qPCR of the AtACT8 gene. The relative expression level of the AtOPR3 gene relative to the expression level of the AtACT8 gene as an internal standard was calculated by the ΔΔCt method. The experiment was repeated 4 to 5 times, and the average was calculated.

[0598] The results are as follows Figure 1 As shown. Compounds 1 and 34 showed the same or higher induction activity of the expression of pest resistance genes as glutamic acid. In particular, compound 1 showed higher induction activity of the expression of pest resistance genes.

[0599] [Example 3] Insect pest inhibitory activity based on various compounds

[0600] In this example, it was confirmed that Ca 2+Compound 1 having signal inducing activity and insect pest resistance gene expression inducing activity was evaluated for whether it substantially maintained insect pest inhibitory activity.

[0601] As for the plant material, Arabidopsis recombinant p35S::GCaMP3 was used, and the first leaf of the cultivated plant body was subjected to incision formation and compound treatment in the same manner as in Example 1. As the compound, compound 1 was used. In addition, sorbitol was used as a negative control, and glutamic acid was used as a positive control. The experiment was carried out in a manner repeated 10 times in each area (independent plants and pests). After 1 hour of compound treatment, the plant body and 2-week-old larvae of the cabbage butterfly (Pieris lapae) were placed in the same container and a 4-hour pest feeding test was carried out. The weight of the plant body and the larvae were measured before and after the test, and the weight of the plant eaten by the pest and the weight increase rate of the pest were evaluated.

[0602] The results are as follows Figure 2 and 3 As shown. The glutamic acid treatment area and the sorbitol treatment area had the same amount of insect damage (the weight of plants eaten by pests and the rate of increase in the weight of pests), and the insect pest inhibitory activity of glutamic acid could not be confirmed. On the other hand, the insect damage (the weight of plants eaten by pests and the rate of increase in the weight of pests) in the compound 1 treatment area was lower than that in the sorbitol treatment area, and a significant insect pest inhibitory activity was confirmed in compound 1.

[0603] [Example 4] Comparison of the insect pest inhibitory activity of glutamic acid derivatives with commercial products

[0604] In this example, the pest inhibitory activity of Compound 1 confirmed to have significant pest inhibitory activity in Example 3 was compared with that of Jasmomate liquid (the active ingredient is jasmone; a representative noxious hormone-like substance), which is the only commercially available resistance inducer against pests.

[0605] As for plant materials, Arabidopsis recombinant p35S::GCaMP3 was used, and the cultivated plants were subjected to the formation of the first leaf incision and compound treatment in the same manner as in Examples 1, 2, and 3. As compounds, compound 1 and Jasmomate were used. Compound 1 was 100 mM, and Jasmomate was used at a 500-fold dilution concentration (0.4 mM as a jasmone concentration) of the normally recommended treatment concentration. Sorbitol was used as a negative control. The test was carried out in a manner repeated 15 times in each area (independent plants and pests). In addition, Jasmomate was sprayed on the leaves (spray area; Jasmomate of the concentration was sprayed twice with a sprayer). The test in the spray area was repeated 10 times (independent plants and pests). One hour after the compound treatment, the plant body and the 2-week-old larvae of the cabbage butterfly (Pierislapae) were placed in the same container and a 4-hour pest feeding test was carried out. The weight of the larvae was measured before and after the test, and the weight gain rate of the pests was evaluated.

[0606] The results are as follows Figure 4 As shown. The amount of insect damage (increase rate of insect weight) in the Jasmomate treatment area (droplet area) was equivalent to that in the sorbitol treatment area, and no insect pest inhibitory activity was confirmed in Jasmomate. On the other hand, in the compound 1 treatment area, the amount of insect damage (increase rate of insect weight) was lower than that in the sorbitol treatment area, and a significant insect pest inhibitory activity was confirmed in Compound 1.

[0607] [Example 5] Insect pest inhibitory activity of glutamic acid derivatives in actual use of crops

[0608] In this example, the presence of Ca in Examples 1 and 2 was confirmed. 2+ Compound 1, which was confirmed to have significant pest inhibitory activity in Examples 3 and 4, was evaluated in leaves of edible crops to see whether it maintained pest inhibitory activity in a concentration range thinner than 100 mM studied in Example 4. Glutamic acid was used as a positive control, and Jasmo mate liquid (the active substance is jasmone; a representative noxious hormone substance), which is the only commercially available resistance inducer against pests, was used as a control. The test was repeated 10 times in each plot (independent plants and pests).

[0609] As plant materials, leaf discs of leaves collected from Japanese mustard seedlings grown in potted culture soil and sown for one month were used, and the second-instar early larvae of the Spodoptera litura (Spodoptera Litura) were used as test organisms. The following solution was used for Compound 1: Silwet L-77 was added to distilled water to obtain a 4000-fold dilution of Silwet-77, and the dilution was used as a solvent to prepare a 1 mM solution. Sorbitol 100 mM or 1 mM was used as a negative control, and glutamate 100 mM or 1 mM was used as a positive control. For the Jasmomate solution, the solvent was set to distilled water, and the Jasmomate solution was set to a 500-fold diluted concentration (0.4 mM as a jasmone concentration) as the generally recommended treatment concentration. The first leaf of the Japanese mustard seedling was collected 1 hour before the treatment with Compound 1, and used A cork borer was used to make leaf discs containing the main vein. The leaf discs were immersed in 50 ml of each test solution prepared in a 100 ml beaker using tweezers, and the compound 1 was treated by immersing the leaf discs one by one for about 10 seconds. The treated leaves were arranged on a paper towel and air-dried for about 20 to 30 minutes. They were then stored one by one in the same test container with 10 second-instar larvae of Spodoptera litura and covered with a lid. The containers were managed at 25±2°C and 16L8D. The test container used was a container obtained in the following manner: in a plastic cup ( Place absorbent cotton on the bottom of RISUPACK's CLEANCUP and Filter paper was placed on the test container and about 10 ml of distilled water was injected into it. After 1 day of stocking, the number of surviving Spodoptera litura larvae in each test container was counted, and photos were taken from a height of 5 cm above the container in a manner that the entire container could be seen with the lid of the test container open. The damaged area (pest feeding area) was calculated using image analysis software (ImageJ), and the average damaged area rate was calculated for each treatment area.

[0610] The results are as follows Figure 5 As shown. The insect pest damage area rate in the Jasmomate treatment area was the same as that in the sorbitol 100mM treatment area, that is, no insect pest inhibitory activity was confirmed in Jasmomate. In the glutamate 100mM treatment area, an insect pest inhibitory tendency was confirmed compared with the sorbitol treatment area. On the other hand, in the compound 1 treatment area, even at a treatment concentration of 1mM, an insect pest inhibitory effect (specifically, a feeding inhibitory effect) equal to or higher than that in the glutamate 100mM treatment area and the Jasmomate treatment area was confirmed.

[0611] Industrial Applicability

[0612] According to the present invention, useful results in the field of agronomy and horticulture, such as controlling plant insect pests, can be obtained.

[0613] <Description of Sequence Listing>

[0614] SEQ ID NO.1~4: Primer

Claims

1. A composition for inducing insect pest resistance in plants or for controlling insect pests in plants, The composition contains the following ingredients (A): (A) a compound represented by the following general formula (I), [Chemical formula 1] In formula (I), n represents an integer from 1 to 3, i.e., 1, 2 or 3, X represents an interatomic bond, an oxygen atom (O), a nitrogen atom (NH) bonded to a hydrogen atom, a nitrogen atom (NMe) bonded to a methyl group, a sulfur atom (S) or a 4-phenoxy group, R 1 represents a hydrogen atom (H), an amidine group or an acyl group, R 2 Represents OR 4 or NHR 4 , R 3 Represents C(=O)-R 5 , sulfonic acid (SO3H), phosphoric acid (PO3H2) or SO2R 6 , R 4 represents a hydrogen atom (H) or an optionally substituted alkyl group having 1 to 8 carbon atoms, R 5 represents an optionally substituted alkyl group having 1 to 8 carbon atoms, an amino acid, a dipeptide, OR 7 or NR 8 R 9 , R 6 represents a methyl group or an optionally substituted phenyl group, R 7 represents a hydrogen atom (H) or an alkyl group having 1 to 8 carbon atoms, R 8 and R 9 Each independently represents a hydrogen atom (H), an optionally substituted alkyl group having 1 to 8 carbon atoms, or an optionally substituted phenyl group.

2. The composition according to claim 1, wherein n is 2.

3. The composition according to claim 1, wherein X is an interatomic bond.

4. The composition according to claim 1, which satisfies any of the following conditions: (1) n is 2, X is an interatomic bond, R 2 is hydroxyl group, R 3 C(=O)-R 5 ; (2) n is 2, X is an interatomic bond, R 1 is a hydrogen atom, R 2 is hydroxyl group, R 3 C(=O)-R 5 , R 5 is a group other than a hydroxyl group; (3) n is 2, X is an interatomic bond, R 1 is a group other than a hydrogen atom, R 2 is hydroxyl group, R 3 C(=O)-R 5 , R 5 is hydroxyl group; (4) n is 2, X is an interatomic bond, R 1 is a hydrogen atom, R 2 is a group other than a hydroxyl group, R 3 It is C(=O)-OH.

5. The composition according to claim 1, wherein The component (A) is selected from the compounds represented by the following formulae: (Compound 1) to (Compound 58) and (Compound 67) to (Compound 75), [Chemical formula 2] [Chemical formula 3] [Chemical formula 4] [Chemical formula 5] [Chemical formula 6] [Chemical formula 7] [Chemical formula 8] [Chemical formula 9] [Chemical formula 10] [Chemical formula 11] [Chemical formula 12] [Chemical formula 13] [Chemical formula 14] [Chemical formula 15] [Chemical formula 16] [Chemical formula 17] [Chemical formula 18] [Chemical formula 19] [Chemical formula 20] [Chemical formula 21] [Chemical formula 22] [Chemical formula 23] [Chemical formula 24] [Chemical formula 25] [Chemical formula 26] [Chemical formula 27] [Chemical formula 28] [Chemical formula 29] [Chemical formula 30] [Chemical formula 31] [Chemical formula 32] [Chemical formula 33] [Chemical formula 34] [Chemical formula 35] [Chemical formula 36] [Chemical formula 37] [Chemical formula 38] [Chemical formula 39] [Chemical formula 40] [Chemical formula 41] [Chemical formula 42] [Chemical formula 43] [Chemical formula 44] [Chemical formula 45] [Chemical formula 46] [Chemical formula 47] [Chemical formula 48] [Chemical formula 49] [Chemical formula 50] [Chemical formula 51] [Chemical formula 52] [Chemical formula 53] [Chemical formula 54] [Chemical formula 55] [Chemical formula 56] [Chemical formula 57] [Chemical formula 58] [Chemical formula 59] [Chemical formula 60] [Chemical formula 61] [Chemical formula 62] [Chemical formula 63] [Chemical formula 64] [Chemical formula 65] [Chemical formula 66] [Chemical formula 67] [Chemical formula 68] 6. The composition according to claim 1, wherein The insect pest is an insect pest caused by an organism classified into the order Lepidoptera, Hemiptera, Coleoptera, Diptera, Orthoptera, Thysanoptera, Tyrannosaurus, Collembola, Acarina, or Stylophora.

7. The composition according to claim 1, wherein The insect pests are classified into the families of Plutella xylostella, Noctuidae, Pyralidae, Leafroller, Leafminer, Fruitborer, Gnaphalidae, Grassworm, Lightmoth, Lymantria, Cicadidae, Rice Pseudopsidae, Psyllidae, Aphididae, Aleyrodidae, Coccoidea, Miridae, Net Bugs, Pentatomidae, Longistidae, Scarabidae, Click Beetle, Coccinella, Cerambycidae, Chilophoridae, Curculionidae, Muscidae, Calliphoridae, Pests caused by organisms of the Sarcophagidae, Tachymycetes, Tephritidae, Gramomycetes, Ornithopoidea, Xiphophidae, Stigmidae, Coneheaded Grasshoppers, Thripidae, Thripidae, Thripidae, Acanthidae, Neotylenchidae, Acanthophoridae, Collembola, Tetranychus, Dermatophytidae, Acaridae, Sarcoptidae, Myxomycetes or Slugidae.

8. The composition according to any one of claims 1 to 7, wherein The plant is a plant of the Poaceae family, the Solanaceae family, the Cucurbitaceae family, the Leguminosae family, the Cruciferae family, the Rosaceae family, the Moraceae family, the Malvaceae family, the Apiaceae family, the Liliaceae family, the Asteraceae family, the Amaranthaceae family, the Ericaceae family, the Vitaceae family, the Rutaceae family, the Rubiaceae family, the Oleaceae family, the Lauraceae family, the Anacardiaceae family, the Sapindaceae family or the Lamiaceae family.

9. A method for inducing insect pest resistance in plants, comprising: applying the following component (A) to the plants: (A) a compound represented by the following general formula (I), [Chemical formula 69] In formula (I), n represents an integer from 1 to 3, i.e., 1, 2 or 3, X represents an interatomic bond, an oxygen atom (O), a nitrogen atom (NH) bonded to a hydrogen atom, a nitrogen atom (NMe) bonded to a methyl group, a sulfur atom (S) or a 4-phenoxy group, R 1 represents a hydrogen atom (H), an amidine group or an acyl group, R 2 Represents OR 4 or NHR 4 , R 3 Represents C(=O)-R 5 , sulfonic acid (SO3H), phosphoric acid (PO3H2) or SO2R 6 , R 4 represents a hydrogen atom (H) or an optionally substituted alkyl group having 1 to 8 carbon atoms, R 5 represents an optionally substituted alkyl group having 1 to 8 carbon atoms, an amino acid, a dipeptide, OR 7 or NR 8 R 9 , R 6 represents a methyl group or an optionally substituted phenyl group, R 7 represents a hydrogen atom (H) or an alkyl group having 1 to 8 carbon atoms, R 8 and R 9 Each independently represents a hydrogen atom (H), an optionally substituted alkyl group having 1 to 8 carbon atoms, or an optionally substituted phenyl group.

10. A method for controlling plant pests, comprising: applying the following component (A) to the plant: (A) a compound represented by the following general formula (I), [Chemical formula 70] In formula (I), n represents an integer from 1 to 3, i.e., 1, 2 or 3, X represents an interatomic bond, an oxygen atom (O), a nitrogen atom (NH) bonded to a hydrogen atom, a nitrogen atom (NMe) bonded to a methyl group, a sulfur atom (S) or a 4-phenoxy group, R 1 represents a hydrogen atom (H), an amidine group or an acyl group, R 2 Represents OR 4 or NHR 4 , R 3 Represents C(=O)-R 5 , sulfonic acid (SO3H), phosphoric acid (PO3H2) or SO2R 6 , R 4 represents a hydrogen atom (H) or an optionally substituted alkyl group having 1 to 8 carbon atoms, R 5 represents an optionally substituted alkyl group having 1 to 8 carbon atoms, an amino acid, a dipeptide, OR 7 or NR 8 R 9 , R 6 represents a methyl group or an optionally substituted phenyl group, R 7 represents a hydrogen atom (H) or an alkyl group having 1 to 8 carbon atoms, R 8 and R 9 Each independently represents a hydrogen atom (H), an optionally substituted alkyl group having 1 to 8 carbon atoms, or an optionally substituted phenyl group.

11. A method for producing a plant, comprising: applying the following component (A) to a plant to cultivate the plant: (A) a compound represented by the following general formula (I), [Chemical formula 71] In formula (I), n represents an integer from 1 to 3, i.e., 1, 2 or 3, X represents an interatomic bond, an oxygen atom (O), a nitrogen atom (NH) bonded to a hydrogen atom, a nitrogen atom (NMe) bonded to a methyl group, a sulfur atom (S) or a 4-phenoxy group, R 1 represents a hydrogen atom (H), an amidine group or an acyl group, R 2 Represents OR 4 or NHR 4 , R 3 Represents C(=O)-R 5 , sulfonic acid (SO3H), phosphoric acid (PO3H2) or SO2R 6 , R 4 represents a hydrogen atom (H) or an optionally substituted alkyl group having 1 to 8 carbon atoms, R 5 represents an optionally substituted alkyl group having 1 to 8 carbon atoms, an amino acid, a dipeptide, OR 7 or NR 8 R 9 , R 6 represents a methyl group or an optionally substituted phenyl group, R 7 represents a hydrogen atom (H) or an alkyl group having 1 to 8 carbon atoms, R 8 and R 9 Each independently represents a hydrogen atom (H), an optionally substituted alkyl group having 1 to 8 carbon atoms, or an optionally substituted phenyl group.

12. The method according to any one of claims 9 to 11, wherein: n is 2.

13. The method according to any one of claims 9 to 11, wherein: X is an interatomic bond.

14. The method according to any one of claims 9 to 11, which satisfies any one of the following conditions: (1) n is 2, X is an interatomic bond, R 2 is hydroxyl group, R 3 C(=O)-R 5 ; (2) n is 2, X is an interatomic bond, R 1 is a hydrogen atom, R 2 is hydroxyl group, R 3 C(=O)-R 5 , R 5 is a group other than a hydroxyl group; (3) n is 2, X is an interatomic bond, R 1 is a group other than a hydrogen atom, R 2 is hydroxyl group, R 3 C(=O)-R 5 , R 5 is hydroxyl group; (4) n is 2, X is an interatomic bond, R 1 is a hydrogen atom, R 2 is a group other than a hydroxyl group, R 3 It is C(=O)-OH.

15. The method according to any one of claims 9 to 11, wherein: The component (A) is selected from the compounds represented by the following formulae: (Compound 1) to (Compound 58) and (Compound 67) to (Compound 75), [Chemical formula 72] [Chemical formula 73] [Chemical formula 74] [Chemical formula 75] [Chemical formula 76] [Chemical formula 77] [Chemical formula 78] [Chemical formula 79] [Chemical formula 80] [Chemical formula 81] [Chemical formula 82] [Chemical formula 83] [Chemical formula 84] [Chemical formula 85] [Chemical formula 86] [Chemical formula 87] [Chemical formula 88] [Chemical formula 89] [Chemical formula 90] [Chemical formula 91] [Chemical formula 92] [Chemical formula 93] [Chemical formula 94] [Chemical formula 95] [Chemical formula 96] [Chemical formula 97] [Chemical formula 98] [Chemical formula 99] [Chemical formula 100] [Chemical Formula 101] [Chemical formula 102] [Chemical formula 103] [Chemical formula 104] [Chemical formula 105] [Chemical formula 106] [Chemical formula 107] [Chemical formula 108] [Chemical formula 109] [Chemical formula 110] [Chemical formula 111] [Chemical formula 112] [Chemical formula 113] [Chemical formula 114] [Chemical formula 115] [Chemical formula 116] [Chemical formula 117] [Chemical formula 118] [Chemical formula 119] [Chemical formula 120] [Chemical formula 121] [Chemical formula 123] [Chemical formula 124] [Chemical formula 125] [Chemical formula 126] [Chemical formula 127] [Chemical formula 128] [Chemical formula 129] [Chemical formula 130] [Chemical formula 131] [Chemical formula 132] [Chemical formula 133] [Chemical formula 134] [Chemical formula 135] [Chemical formula 136] [Chemical formula 137] [Chemical formula 138] 16. The method according to any one of claims 9 to 11, wherein: The component (A) is used in the form of a liquid containing the component (A) at a concentration of 0.1 to 1000 mM.

17. The method according to any one of claims 9 to 11, wherein: The insect pest is an insect pest caused by an organism classified into the order Lepidoptera, Hemiptera, Coleoptera, Diptera, Orthoptera, Thysanoptera, Tyrannosaurus, Collembola, Acarina, or Stylophora.

18. The method according to any one of claims 9 to 11, wherein: The insect pests are classified into the families of Plutella xylostella, Noctuidae, Pyralidae, Leafroller, Leafminer, Fruitborer, Gnaphalidae, Grassworm, Lightmoth, Lymantria, Cicadidae, Rice Pseudopsidae, Psyllidae, Aphididae, Aleyrodidae, Coccoidea, Miridae, Net Bugs, Pentatomidae, Longistidae, Scarabidae, Click Beetle, Coccinella, Cerambycidae, Chilophoridae, Curculionidae, Muscidae, Calliphoridae, Pests caused by organisms of the Sarcophagidae, Tachymycetes, Tephritidae, Gramomycetes, Ornithopoidea, Xiphophidae, Stigmidae, Coneheaded Grasshoppers, Thripidae, Thripidae, Thripidae, Acanthidae, Neotylenchidae, Acanthophoridae, Collembola, Tetranychus, Dermatophytidae, Acaridae, Sarcoptidae, Myxomycetes or Slugidae.

19. The method according to any one of claims 9 to 11, wherein: The plant is a plant of the Poaceae family, the Solanaceae family, the Cucurbitaceae family, the Leguminosae family, the Cruciferae family, the Rosaceae family, the Moraceae family, the Malvaceae family, the Apiaceae family, the Liliaceae family, the Asteraceae family, the Amaranthaceae family, the Ericaceae family, the Vitaceae family, the Rutaceae family, the Rubiaceae family, the Oleaceae family, the Lauraceae family, the Anacardiaceae family, the Sapindaceae family or the Lamiaceae family.

Images