CN110078721B - Triazine-containing pentadiene ketone compound and preparation method and application thereof - Google Patents

Triazine-containing pentadiene ketone compound and preparation method and application thereof Download PDF

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CN110078721B
CN110078721B CN201910449787.2A CN201910449787A CN110078721B CN 110078721 B CN110078721 B CN 110078721B CN 201910449787 A CN201910449787 A CN 201910449787A CN 110078721 B CN110078721 B CN 110078721B
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triazine
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CN110078721A (en
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薛伟
汤旭
陈梅
贺军
苏时军
吴佳祥
柳立伟
贺鸣
王俊
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Guizhou University
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    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/64—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with three nitrogen atoms as the only ring hetero atoms
    • A01N43/707—1,2,3- or 1,2,4-triazines; Hydrogenated 1,2,3- or 1,2,4-triazines
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D253/00—Heterocyclic compounds containing six-membered rings having three nitrogen atoms as the only ring hetero atoms, not provided for by group C07D251/00
    • C07D253/02—Heterocyclic compounds containing six-membered rings having three nitrogen atoms as the only ring hetero atoms, not provided for by group C07D251/00 not condensed with other rings
    • C07D253/06—1,2,4-Triazines
    • C07D253/065—1,2,4-Triazines having three double bonds between ring members or between ring members and non-ring members
    • C07D253/07—1,2,4-Triazines having three double bonds between ring members or between ring members and non-ring members with hetero atoms, or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Agronomy & Crop Science (AREA)
  • Pest Control & Pesticides (AREA)
  • Plant Pathology (AREA)
  • Health & Medical Sciences (AREA)
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  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)

Abstract

The invention relates to a triazine-containing pentadiene ketone compound and a preparation method and application thereof. The compound is shown as a formula A. Wherein X is selected from O, R is phenyl, substituted heterocyclic radical, R is1Is a hydrogen atom or a methoxy group, R2Is phenyl, substituted phenyl or C1-C6 alkyl, etc. The compound has better control effect on ralstonia solanacearum, citrus bacterial infection and rice bacterial blight.

Description

Triazine-containing pentadiene ketone compound and preparation method and application thereof
Technical Field
The invention relates to the technical field of chemical industry, in particular to a triazine-containing 1, 4-pentadiene-3-ketone derivative, a preparation method of the triazine-containing 1, 4-pentadiene-3-ketone derivative, and application of the triazine-containing 1, 4-pentadiene-3-ketone derivative in the aspect of antibacterial activity.
Background
The natural active molecules and the derivatives thereof have the characteristics of unique structure, novel action mode, low toxicity to human and livestock and environmental friendliness, and have great significance in the discovery process of pesticide lead compounds. Curcumin, a polyphenol compound derived from turmeric, is widely used as a spice, a food preservative, monosodium glutamate and a dye. The 1, 4-pentadiene ketone compound is an important curcumin derivative, and has broad-spectrum biological activity such as insecticidal activity, bacteriostasis, plant virus resistance, cancer resistance, inflammation diminishing and oxidation resistance, and plays an important role in research and development of pesticides.
Xue et al (Xue Wei, Gong Hua Yu, Fengqian, Zhao hong Ju, Li Hai Chang, Han Fei. synthesis of oxime ester curcumin derivatives and antibacterial activity research [ J ] chemical reagent, 2013, 35: 201-: when the concentration is 500mg/L, the series of compounds have certain inhibition effect on three germs.
Naxighai et al (Ganxuahai, Hudei, Li Pepper, Wujian, Chen schwara, Song Bao an. research on the design, synthesis, antiviral activity and three-dimensional quantitative structure-activity relationship of novel 1, 4-pentadiene-3-one derivatives containing 1, 3, 4-oxadiazole moiety [ J ] pest management science, 2016, 72: 534-.
Zhangjuping (Zhangjuping, Li Pu, Wang Yi, Zhang Chen Li Juan, Tangxu Xue, Heming, Xuehei, synthesis and antibacterial activity of 1, 4-pentadiene-3-ketone derivatives containing benzotriazinone, advanced chemical bulletin, 2018, 39: 1455-.
1, 2, 4-triazine is an important nitrogen-containing heterocycle, and the special structure and the property of the heterocycle enable the heterocycle to have the advantages of high chemical activity, many reaction sites and the like. Because the 1, 2, 4-triazine has the advantages of low price, easy obtaining, easy storage, stable structure and the like, the 1, 2, 4-triazine and the derivative thereof have the advantages of a variety with a few activities such as bacteriostasis, anti-inflammation, analgesia, HIV-1 resistance, cancer resistance, diabetes resistance, malaria resistance and the like, low toxicity, low residue and the like. At present, the molecular design, synthesis and biological activity research of the compounds are one of the hot spots for creating pesticides and medicines.
In 2015, Tamboli et al (J.enzyme. inhib. Med. chem. 2015, 5: 1475. 6366.) synthesized a series of 5, 6-diphenyl-1, 2, 4-triazine compounds containing morpholine ethylamine, and the synthesized compounds were subjected to anti-platelet in vitro, in vitro and in vivo activity determination, and the results show that the compounds have good antithrombotic activity and the synthesized compounds have good in vivo antithrombotic property. IC thereof50Is superior to the contrast medicine aspirin.
Fu et al (Eur.J.Med.chem, 2017, 138: 1076-1088.) introduced 1, 2, 3-triazole into 5, 6-diphenyl-1, 2, 4-triazine by active group splicing in 2017 to synthesize a series of new 5, 6-diphenyl-1, 2, 4-triazine compounds containing 1, 2, 3-triazole. The synthesized compounds are tested for the anti-tumor activity (MGC-803, EC-109 and PC-3)), and the results show that the compounds have good anti-tumor activity, wherein the lowest half inhibitory concentration IC of the compounds507.59. mu.M is better than the control 5-fluorouracil.
In 2017, Wang et al (bioorg.Med.chem.Lett, 2017, 27: 1115-5012.46 +/-0.13 mu M better than acarbose (IC) serving as a control drug50＝817.38±6.27μM)。
At present, no report about the introduction of triazine-containing compounds into 1, 4-pentadiene-3-ketone structures and the test of bacteriostasis is found.
Disclosure of Invention
The invention aims to overcome the defects and provide triazine-containing 1, 4-pentadiene-3-ketone compounds and derivatives thereof.
One of the objects of the present invention is to provide triazine-containing 1, 4-pentadien-3-ones or stereoisomers thereof, or salts or solvates thereof.
Another object of the present invention is to provide an intermediate compound for preparing the above compound or a stereoisomer thereof, or a salt or solvate thereof, and a preparation method thereof.
It is still another object of the present invention to provide a composition comprising the above compound or a stereoisomer thereof, or a salt or solvate thereof.
It is a further object of the present invention to provide the above compounds or stereoisomers thereof, or salts or solvates thereof, or the use of said compositions.
Another object of the present invention is to provide a method for controlling agricultural pests using the above compound or a stereoisomer thereof, or a salt or solvate thereof, or the composition.
In order to realize the purpose, the invention adopts the following technical scheme:
a triazine-containing 1, 4-pentadien-3-one compound or a stereoisomer thereof, or a salt or solvate thereof, the compound having a structure represented by general formula a:
Figure BSA0000183806020000031
wherein the content of the first and second substances,
r is independently selected from one or more of hydrogen, deuterium, optionally substituted or unsubstituted alkyl, optionally substituted or unsubstituted alkenyl, optionally substituted or unsubstituted alkynyl, optionally substituted or unsubstituted alkoxy, optionally substituted or unsubstituted cycloalkyl, optionally substituted or unsubstituted aryl, and optionally substituted or unsubstituted heteroaryl;
R1independently selected from hydrogen, deuterium, halogen, optionally substituted or unsubstituted alkyl,One or more of optionally substituted or unsubstituted alkenyl, optionally substituted or unsubstituted alkynyl, optionally substituted or unsubstituted alkoxy, optionally substituted or unsubstituted cycloalkyl, and optionally substituted or unsubstituted aryl;
R2the same or different groups are independently selected from one or more of hydrogen, deuterium, halogen, optionally substituted or unsubstituted alkyl, optionally substituted or unsubstituted alkenyl, optionally substituted or unsubstituted alkynyl, optionally substituted or unsubstituted alkoxy, optionally substituted or unsubstituted cycloalkyl, optionally substituted or unsubstituted aryl, and optionally substituted or unsubstituted heteroaryl;
x is independently selected from O, S or NH.
Preferably, R is independently selected from one or more of hydrogen, deuterium, alkyl, alkenyl, alkynyl, alkoxy, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl; more preferably, R is independently selected from hydrogen, deuterium, C1-C6Alkyl radical, C1-C6Alkoxy radical, C1-C6Alkenyl radical, C1-C6Alkynyl, substituted or unsubstituted C6-C15Aryl, substituted or unsubstituted C6-C10One or more of heteroaryl, wherein said substituted refers to being substituted by C1-C6Alkyl radical, C1-C6Alkoxy radical, C1-C6Alkenyl radical, C1-C6Alkynyl, amino, hydroxyl, halogen; most preferably, R is independently selected from the group consisting of hydrogen, deuterium, nitro, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, neopentyl, propenyl, allyl, butenyl, pentenyl, hexenyl, propynyl, butynyl, pentynyl, hexynyl, methoxy, ethoxy, propoxy, butoxy, phenyl, chlorophenyl, bromophenyl, fluorophenyl, dichlorophenyl, dibromophenyl, difluorophenyl, nitrophenyl, dinitrophenyl, methoxyphenyl, dimethoxyphenyl, methylphenyl, dimethylphenyl, aminophenyl, hydroxyphenyl, benzyl, o-fluorobenzyl, m-fluorobenzyl, p-fluorobenzyl, o-bromobenzyl, m-bromobenzyl, p-bromobenzylA group, o-chlorobenzyl, m-chlorobenzyl, p-chlorobenzyl, naphthyl, phenanthryl, pyridyl, thienyl, o-fluoropyridyl, m-fluoropyridyl, o-bromopyridyl, m-bromopyridyl, o-chloropyridyl, o-fluorothienyl, m-fluorothienyl, o-fluorofuryl, m-fluorofuryl, o-fluorotetrahydrofuryl, m-fluorotetrahydrofuryl, o-bromothienyl, m-bromothienyl, o-bromofuryl, m-bromofuryl, o-bromotetrahydrofuryl, m-bromotetrahydrofuryl, o-chlorothienyl, m-chlorothienyl, o-chlorofuryl, m-chlorofuryl, o-chlorotetrahydrofuryl, m-chlorotetrahydrofuryl, o-hydroxybenzyl, m-hydroxybenzyl, p-hydroxybenzyl, o-aminobenzyl, m-aminobenzyl, p-methylbenzyl, o-hydroxypyridine, m-hydroxypyridyl, p-hydroxypyridyl, o-hydroxybenzyl, o-chloropyridyl, o-bromopyridyl, o-bromofuryl, o-and m-chlorobenzyl, One or more of o-aminothienyl, m-aminothienyl, o-hydroxyfuryl, m-hydroxyfuryl, o-hydroxytetrahydrofuranyl, m-hydroxytetrahydrofuranyl, o-methylfuryl, m-methylfuryl, o-methyltetrahydrofuryl, m-methyltetrahydrofuryl, o-furanmethylene, m-furanmethylene, o-tetrahydrofurmethylene, m-tetrahydrofurmethylene;
preferably, R1Independently selected from one or more of hydrogen, deuterium, halogen, alkyl, alkenyl, alkynyl, alkoxy, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, or heterocycle; more preferably, R1Independently selected from hydrogen, deuterium, C1-C6Alkyl radical, C1-C6Alkenyl radical, C1-C6Alkynyl, C1-C6Alkoxy, substituted or unsubstituted C6-C15Aryl, substituted or unsubstituted C6-C10One or more of heteroaryl, wherein said substituted refers to being substituted by C1-C6Alkyl radical, C1-C6Alkoxy, amino, hydroxy, halogen substitution; most preferably, R1Independently selected from hydrogen, deuterium, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, neopentyl, propenyl, allylOne or more of yl, butenyl, pentenyl, hexenyl, propynyl, butynyl, pentynyl, hexynyl, methoxy, ethoxy, propoxy, butoxy, phenyl, chlorophenyl, bromophenyl, fluorophenyl, tolyl, aminophenyl, hydroxyphenyl, benzyl, o-fluorobenzyl, m-fluorobenzyl, p-fluorobenzyl, o-bromobenzyl, m-bromobenzyl, p-bromobenzyl, o-chlorobenzyl, m-chlorobenzyl, p-chlorobenzyl, naphthyl, phenanthryl, pyridyl;
preferably, R2The same or different are independently selected from one or more of hydrogen, deuterium, halogen, alkyl, alkenyl, alkynyl, alkoxy, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl; more preferably, R2Independently selected from hydrogen, deuterium, C1-C6Alkyl radical, C1-C6Alkoxy radical, C1-C6Alkenyl radical, C1-C6Alkynyl, substituted or unsubstituted C6-C15Aryl, substituted or unsubstituted C6-C10One or more of heteroaryl, wherein said substituted refers to being substituted by C1-C6Alkyl radical, C1-C6Alkoxy radical, C1-C6Alkenyl radical, C1-C6Alkynyl, amino, hydroxyl, halogen; most preferably, R2Independently selected from the group consisting of hydrogen, deuterium, nitro, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, neopentyl, propenyl, allyl, butenyl, pentenyl, hexenyl, propynyl, butynyl, pentynyl, hexynyl, methoxy, ethoxy, propoxy, butoxy, phenyl, chlorophenyl, bromophenyl, fluorophenyl, nitrophenyl, methoxyphenyl, methylphenyl, aminophenyl, hydroxyphenyl, benzyl, o-fluorobenzyl, m-fluorobenzyl, p-fluorobenzyl, o-bromobenzyl, m-bromobenzyl, p-bromobenzyl, o-chlorobenzyl, m-chlorobenzyl, p-chlorobenzyl, naphthyl, phenanthryl, pyridyl, thienyl, o-fluoropyridyl, m-fluoropyridyl, o-bromopyridyl, m-chloropyridyl, o-fluorothienyl, m-fluorothienyl, o-fluorofuryl, M-fluoro furyl, o-fluoroTetrahydrofuranyl, m-fluorotetrahydrofuranyl, o-bromothienyl, m-bromothienyl, o-bromofuryl, m-bromofuryl, o-bromotetrahydrofuranyl, m-bromotetrahydrofuranyl, o-chlorothioenyl, m-chlorothioenyl, o-chlorofuryl, m-chlorofuryl, o-chlorotetrafuryl, m-chlorotetrafuryl, o-hydroxybenzyl, m-hydroxybenzyl, p-hydroxybenzyl, o-aminobenzyl, m-aminobenzyl, p-methylbenzyl, o-methylbenzyl, p-methylbenzyl, o-hydroxypyridine, m-hydroxypyridinyl, p-hydroxypyridinyl, o-aminothienyl, m-aminothienyl, o-hydroxyfuryl, m-hydroxyfuryl, o-hydroxytetrafuryl, m-hydroxytetrafuryl, o-methylfuryl, m-methylfuryl, o-methyltetrahydrofuranyl, m-methyltetrahydrofuranyl, o-furanmethylene, m-furanmethylene, o-bromofuryl, m-bromofuryl, o-bromofuryl, m-chlorobenzyl, o-hydrofanyl, o-hydroxybenzyl, o-chlorobenzyl, o-furyl, o-chlorobenzyl, o-chloro-furyl, o-chlorobenzyl, o-hydroxybenzyl, o-hydroxy-hydroxybenzyl, o-hydroxy-furyl, o-furyl, o-benzyl-bromo-furyl, o-hydroxy-furyl, o-bromo-hydroxy-bromo-furyl, o-bromo-hydroxy-bromo-hydroxy-bromo-hydroxy-benzyl-hydroxy-bromo-hydroxy-bromo-hydroxy-benzyl, o-benzyl-hydroxy-benzyl, o-hydroxy-benzyl, o-benzyl-hydroxy-benzyl, o-hydroxy-benzyl-hydroxy, One or more of ortho-tetrahydrofuranyl methylene, meta-tetrahydrofuranyl methylene;
further preferred are compounds selected from the following:
Figure BSA0000183806020000051
Figure BSA0000183806020000061
the invention also provides an intermediate compound for preparing the triazine-containing 1, 4-pentadiene-3-ketone compound or the stereoisomer thereof, or the salt thereof or the solvate thereof, which is shown as the following formula:
Figure BSA0000183806020000062
r, R therein1、R2And X is as described above.
The invention provides a preparation method of triazine-containing 1, 4-pentadiene-3-ketone compounds or stereoisomers thereof, or salts or solvates thereof, which is characterized by comprising the following steps:
Figure BSA0000183806020000063
preferably, the method further comprises the following steps:
Figure BSA0000183806020000064
more preferably, the method comprises the following steps:
Figure BSA0000183806020000065
most preferably, the following steps are included:
Figure BSA0000183806020000066
Figure BSA0000183806020000071
the invention provides a composition, which is characterized by comprising the compound or a stereoisomer thereof, or a salt or a solvate thereof, and an agriculturally acceptable auxiliary agent or a bactericide, an insecticide or a herbicide; preferably, the formulation of the composition is independently selected from Emulsifiable Concentrates (EC), Dusts (DP), Wettable Powders (WP), Granules (GR), Aqueous Solutions (AS), Suspension Concentrates (SC), ultra low volume sprays (ULV), Soluble Powders (SP), Microcapsules (MC), smoking agents (FU), aqueous Emulsions (EW), water dispersible granules (WG).
The invention provides the use of the compound or stereoisomer thereof, or salt or solvate thereof, or the composition for controlling agricultural pests, preferably bacterial or fungal diseases of plants; more preferably, the agricultural pests are plant leaf blight and plant canker; most preferably, the agricultural pests are rice bacterial blight, tobacco bacterial wilt, tobacco mosaic disease, cucumber bacterial blight, konjac bacterial blight, citrus canker, grape canker, tomato canker, kiwi canker, apple canker, cucumber gray mold, pepper wilt, rape sclerotinia rot, wheat scab, potato late blight, pepper wilt, blueberry root rot, wheat scab, potato late blight, rape sclerotinia rot and dragon fruit anthracnose.
The invention provides a method for preventing and controlling agricultural pests, which enables the compound or the stereoisomer thereof, the salt thereof or the solvate thereof, or the composition to act on the pests or the living environment thereof; preferably, the agricultural pest is a bacterial or fungal disease of a plant; more preferably, the agricultural pests are rice bacterial blight, tobacco bacterial wilt, tobacco mosaic disease, cucumber bacterial blight, konjac bacterial blight, citrus canker, grape canker, tomato canker, kiwi canker, apple canker, cucumber gray mold, pepper wilt, rape sclerotinia rot, wheat scab, potato late blight, pepper wilt, blueberry root rot, wheat scab, potato late blight, rape sclerotinia rot and dragon fruit anthracnose.
The present invention provides a method for protecting a plant from an agricultural pest comprising the method step wherein the plant is contacted with the compound or stereoisomer thereof, or salt or solvate thereof, or the composition.
The term "alkyl" as used herein is intended to include both branched and straight chain saturated hydrocarbon radicals having the specified number of carbon atoms. E.g. "C1-10Alkyl "(or alkylene) groups are intended to be C1, C2, C3, C4, C5, C6, C7, C8, C9 and C10 alkyl groups. In addition, for example "C1-6Alkyl "denotes an alkyl group having 1 to 6 carbon atoms. Alkyl groups may be unsubstituted or substituted such that one or more of its hydrogen atoms are replaced with another chemical group. Examples of alkyl groups include, but are not limited to, methyl (Me), ethyl (Et), propyl (e.g., n-propyl and isopropyl), butyl (e.g., n-butyl, isobutyl, t-butyl), pentyl (e.g., n-pentyl, isopentyl, neopentyl), and the like. And, when mention is made of hexyl, heptyl, octylWhen used, all isomers are included, except for n-hexyl, n-heptyl, and n-octyl.
"alkenyl" is a hydrocarbon group that includes both straight and branched chain structures and has one or more carbon-carbon double bonds that occur at any stable point in the chain. E.g. "C2-6Alkenyl "(or alkenylene) is intended to include C2, C3, C4, C5, and C6 alkenyl. Examples of alkenyl groups include, but are not limited to, ethenyl, 1-propenyl, 2-butenyl, 3-butenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 5-hexenyl, 2-methyl-2-propenyl, 4-methyl-3-pentenyl, and the like.
"alkynyl" is intended to include both straight and branched chain hydrocarbons having one or more carbon-carbon triple bonds at any stable point in the chain. E.g. "C2-6Alkynyl "(or alkynylene) is intended to include C2, C3, C4, C5, and C6 alkynyl; such as ethynyl, propynyl, butynyl, pentynyl, hexynyl and the like.
The term "substituted" as used herein means that any one or more hydrogen atoms on the designated atom or group is replaced with the designated group of choice, provided that the general valence of the designated atom is not exceeded. If not otherwise stated, substituents are named to the central structure. For example, it is understood that when (cycloalkyl) alkyl is a possible substituent, the point of attachment of the substituent to the central structure is in the alkyl moiety. As used herein, a cyclic double bond is a double bond formed between two adjacent ring atoms (e.g., C ═ C, C ═ N or N ═ N).
When referring to substitution, especially polysubstitution, it is meant that the various substituents are substituted at various positions on the indicated group, e.g., dichlorophenyl means 1, 2-dichlorophenyl, 1, 3-dichlorophenyl, and 1, 4-dichlorophenyl; in addition, the dichlorophenyl group may be attached to the compound host structure at any position.
Combinations of substituents and or variables are permissible only if such combinations result in stable compounds or useful synthetic intermediates.
The term "aryl" refers to monocyclic or bicyclic aromatic hydrocarbon groups having 6 to 12 carbon atoms in the ring portion, such as phenyl and naphthyl, each of which may be substituted. When referring to mono-or poly-substituted aryl, as described above, it is meant that one or more substituents are substituted at various positions on the indicated group, which may be attached to the compound's main structure at any unsubstituted position; for example, dichlorophenyl refers to 1, 2-dichlorophenyl, 1, 3-dichlorophenyl and 1, 4-dichlorophenyl, and any unsubstituted position of 1, 2-dichlorophenyl, 1, 3-dichlorophenyl and 1, 4-dichlorophenyl is linked to the main structure of the compound.
The term "halogen" or "halogen atom" refers to chlorine, bromine, fluorine and iodine.
The term "haloalkyl" refers to a substituted alkyl having one or more halo substituents. For example, "haloalkyl" includes mono-, di-and trifluoromethyl; even if the halo in a haloalkyl group is specified as fluoro, chloro, bromo, iodo, the same refers to a substituted alkyl group having one or more fluoro, chloro, bromo, iodo substituents.
The term "heteroaryl" refers to substituted and unsubstituted aromatic 5 or 6 membered monocyclic groups, 9-or 10-membered bicyclic groups, and 11 to 14 membered tricyclic groups having at least one heteroatom (O, S or N) in at least one ring, said heteroatom containing ring preferably having 1, 2 or 3 heteroatoms selected from O, S and N. The heteroatom-containing heteroaryl groups can contain one or two oxygen or sulfur atoms per ring and/or from 1 to 4 nitrogen atoms, provided that the total number of heteroatoms in each ring is 4 or less and each ring has at least one carbon atom. The fused rings completing the bicyclic and tricyclic groups may contain only carbon atoms and may be saturated, partially saturated, or unsaturated. The nitrogen and sulfur atoms may optionally be oxidized and the nitrogen atoms may optionally be quaternized. Bicyclic or tricyclic heteroaryl groups must include at least one fully aromatic ring, and the other fused rings may be aromatic or non-aromatic. The heteroaryl group may be attached at any available nitrogen or carbon atom of any ring. If the other ring is cycloalkyl or heterocyclic, it is additionally optionally substituted with ═ O (oxygen), as valency permits. When referring to any heteroaryl group, the heteroaryl group can be attached at any position to the main body position of the compound, such as thienyl, meaning that the 2, 3, 4, 5 positions of the thienyl group can all be attached to the main body position of the compound. When heteroaryl is substituted, especially polysubstituted, it is meant that one or more substituents are substituted at various positions on the indicated group, e.g. chlorothienyl refers to 2-chlorothienyl, 3-chlorothienyl, 4-chlorothienyl, 5-chlorothienyl; dichlorothienyl refers to 2, 3-dichlorothienyl, 2, 4-dichlorothienyl, 2, 5-chlorothienyl, 3, 4-chlorothienyl, 3, 5-chlorothienyl and 4, 5-chlorothienyl, and any unsubstituted position in the mono-or poly-substituted thienyl is connected to the main structure of the compound.
Exemplary monocyclic heteroaryls include pyrrolyl, pyrazolyl, pyrazolinyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, thiadiazolyl, furanyl, thienyl, oxadiazolyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, triazinyl, and the like.
Exemplary bicyclic heteroaryls include indolyl, benzothiazolyl, benzodioxolyl, benzoxazolyl, benzothienyl, quinolinyl, tetrahydroisoquinolinyl, isoquinolinyl, benzimidazolyl, benzofuranyl, indolizinyl, benzofuranyl, chromonyl, coumarinyl, benzofuranyl, cinnolinyl, quinoxalinyl, indazolyl, pyrrolopyridyl, fluoropyridinyl, dihydroisoindolyl, tetrahydroquinolinyl, and the like.
The compounds of the invention are understood to include both the free form and salts thereof, unless otherwise indicated. The term "salt" means an acid and/or base salt formed from an inorganic and/or organic acid and a base. In addition, the term "salt" may include zwitterions (internal salts), such as when the compound of formula I contains a basic moiety, such as an amine or pyridine or imidazole ring, and an acidic moiety, such as a carboxylic acid. Pharmaceutically acceptable (i.e., non-toxic, physiologically acceptable) salts are preferred, such as acceptable metal and amine salts, wherein the cation does not contribute significantly to the toxicity or biological activity of the salt. However, other salts may be useful, such as separation or purification steps in the preparation process, and are therefore included within the scope of the present invention.
Preferably, C1-C10Alkyl refers to methyl, ethyl, propyl, butyl,Pentyl, hexyl, heptyl, octyl, nonyl, decyl and isomers thereof; c1-C10Alkoxy refers to methoxy, ethoxy, propoxy, butoxy, pentyloxy, hexyloxy, heptyloxy, octyloxy, nonyloxy, decyloxy and isomers thereof; c2-C5Alkenyl refers to ethenyl, propenyl, allyl, butenyl, pentenyl, and isomers thereof. Similarly, C1-C5Alkyl refers to methyl, ethyl, propyl, butyl, pentyl and isomers thereof; c1-C5Alkoxy refers to methoxy, ethoxy, propoxy, butoxy, pentoxy and isomers thereof;
when substituents are mentioned, such as alkenyl, alkynyl, alkyl, halo, aryl, heteroaryl, alkoxy, cycloalkyl, hydroxy, amino, mercapto, phosphino, or when these substituents are specifically alkenyl, alkynyl, alkyl, halo, aryl, heteroaryl, alkoxy, cycloalkyl, hydroxy, amino, mercapto, phosphino, one to three of the above substituents are meant. For example, methylphenyl refers to phenyl substituted with one to three methyl groups
More preferably, the present invention also provides a method for preparing the compound:
the synthetic route is as follows:
(1) synthesis of 5, 6-dimethyl-1, 2, 4-triazine-3-thiol or 5, 6-diphenyl-1, 2, 4-triazine-3-thiol from 2, 3-butanedione or benzil with thiosemicarbazide (intermediate 1):
Figure BSA0000183806020000101
(2) preparation of 4- (hydroxyphenyl) -3-buten-2-one (intermediate 2) from acetone and 4-hydroxybenzaldehyde under basic conditions;
(3) preparing 1-substituted aryl-5- (4-hydroxyphenyl) -1, 4-pentadiene-3-one (intermediate 3) from substituted aromatic aldehyde and 4- (hydroxyphenyl) -3-buten-2-one (intermediate 2) under alkaline conditions;
Figure BSA0000183806020000102
(4) 1-substituted aryl-5- (4- (2-bromoethoxy) phenyl) -1, 4-pentadien-3-one (intermediate 4) was prepared from 1-substituted aryl-5- (4-hydroxyphenyl) -1, 4-pentadien-3-one (intermediate 3) and dibromoethane in the presence of potassium carbonate as a catalyst and acetonitrile as a solvent:
Figure BSA0000183806020000103
(5) 1-substituted aryl-5- (4- (2-bromoethoxy) phenyl) -1, 4-pentadien-3-one (intermediate 4) and 5, 6-dimethyl-1, 2, 4-triazin-3-mercaptoalcohol or 5, 6-diphenyl-1, 2, 4-triazin-3-mercaptoalcohol (intermediate 1), triazine-containing 1, 4-pentadien-3-one derivatives (target compound A) were prepared using potassium carbonate as a catalyst and N, N-Dimethylformamide (DMF) as a solvent as follows:
Figure BSA0000183806020000104
compared with the prior art, the invention has obvious beneficial effects, and the technical scheme can show that: the invention takes 2, 3-butanedione, benzil, thiosemicarbazide and the like as raw materials to generate triazine, takes acetone and 4-hydroxybenzaldehyde as raw materials to generate 4- (hydroxyphenyl) -3-butene-2-ketone, takes substituted aromatic aldehyde and 4- (hydroxyphenyl) -3-butene-2-ketone as raw materials to generate 1-substituted aryl-5- (4-hydroxyphenyl) -1, 4-pentadiene-3-ketone, takes 1-substituted aryl-5- (4-hydroxyphenyl) -1, 4-pentadiene-3-ketone as raw materials to react with dibromoethane, and the generated product reacts with triazine to obtain the triazine-containing 1, 4-pentadiene-3-ketone derivative. The invention introduces triazine group with excellent activity into the structure of 1, 4-pentadiene-3-ketone, namely, the triazine structure is connected on the 4-hydroxyl of 1, 4-pentadiene-3-ketone. A series of triazine-containing 1, 4-pentadiene-3-ketone compounds are synthesized, and the activity test of the plant-inhibiting pathogenic bacteria of the synthesized triazine-containing 1, 4-pentadiene-3-ketone derivatives shows that the compounds have excellent activity of inhibiting plant pathogenic bacteria (ralstonia solanacearum, citrus canker pathogenic bacteria and rice leaf blight pathogenic bacteria), and can be used for preparing agricultural bactericides.
Examples
The invention is further illustrated by the following examples. It should be understood that the method described in the examples is only for illustrating the present invention and not for limiting the present invention, and that simple modifications of the preparation method of the present invention based on the concept of the present invention are within the scope of the claimed invention. All the starting materials and solvents used in the examples are commercially available products.
Example 1
(1E, 4E) -1- (4- (2- ((5, 6-diphenyl-1, 2, 4-triazine-3-mercaptoethoxy) phenyl) -5- (2-thiophene) -5-substituted-1, 4-pentadien-3-one (target Compound A1):
Figure BSA0000183806020000111
the preparation method comprises the following steps:
(1) preparation of 5, 6-diphenyl-1, 2, 4-triazine-3-thiol (intermediate 1):
benzil (1.5g) and 35mL glacial acetic acid are added into a 100mL three-neck flask, thiosemicarbazide (0.65g) is dissolved in 25mL hot water, then a mixed system is added into the three-neck flask, the system is stirred for 4 hours at the temperature of 100 ℃, and after the reaction is finished, yellow solid is obtained by thermal filtration, and the yield is 78%.
(2) Preparation of 4- (hydroxyphenyl) -3-buten-2-one (intermediate 2):
4-hydroxybenzaldehyde (6.1g) was added to 60mL of acetone, stirred for about 15min, and after ice-cooling the reaction system for about 30min, about 100mL of 5% NaOH solution was added to the system, after the dropwise addition, the ice-cooling chamber was removed, and the mixture was stirred at room temperature for about 24 h. After the reaction is finished, transferring the system to a 500mL beaker, adding a proper amount of ice water, adjusting the pH of the system to be about 5-6 by using a 5% dilute hydrochloric acid solution, separating out a large amount of yellow solid, pumping out the solid, and finally recrystallizing by using an ethanol/water system to obtain the yellow solid with the yield of 65%.
(3) Preparation of 1- (4-hydroxyphenyl) -5- (2-thiophene) -1, 4-pentadien-3-one (intermediate 3):
1- (4-hydroxyphenyl) -5- (2-thiophene) -1, 4-pentadiene-3-one (3.0g), 2-thiophenecarboxaldehyde (2.24mL) and 50mL of ethanol were added to a 250mL three-necked flask, and after stirring for about 30min, 60mL of a 5% NaOH solution was added to the system, after completion of the dropwise addition, the ice bath was removed, and the mixture was stirred at room temperature for about 24 hours. After the reaction is finished, transferring the system to a 500mL beaker, adding a proper amount of ice water, adjusting the pH of the system to be about 5-6 by using a 5% dilute hydrochloric acid solution, separating out a large amount of yellow solid, and extracting the solid to obtain the yellow solid with the yield of 80%.
(4) Preparation of 1- (4- (2-bromoethoxy) phenyl) -5- (2-thiophene) -1, 4-pentadien-3-one (intermediate 4):
1- (4- (2-Bromoethoxy) phenyl) -5- (2-thiophene) -1, 4-pentadien-3-one (1.6g), K were added to a 100mL round-bottomed flask in this order2CO3(2.25g) and 60mL acetonitrile, then the mixture was refluxed at 80 ℃ for 1h, 2.80mL dibromoethane was added dropwise, and the reflux was continued at 80 ℃ for 7h, and the reaction was followed by TLC (ethyl acetate: petroleum ether: 1: 2, V/V). After the reaction was terminated, the reaction mixture was dispersed in 50mL of water, extracted with ethyl acetate (3X 25mL), and the organic layers were combined, washed with saturated brine (3X 40mL) and anhydrous Na2SO4Drying, removal of the solvent under reduced pressure and purification by column chromatography under reduced pressure (petroleum ether: ethyl acetate 2: 1, V/V) gave a yellow solid (intermediate 4) in yield: 53 percent.
(5) Preparation of (1E, 4E) -1- (4- (2- ((5, 6-diphenyl-1, 2, 4-triazine-3-mercaptoethoxy) phenyl) -5- (2-thiophene) -5-substituted-1, 4-pentadien-3-one (target compound a 1):
into a 100mL single neck round bottom flask was added 0.5g of 5, 6-diphenyl-1, 2, 4-triazine-3-mercaptol (intermediate 1), K2CO3(1.33g) and 60mL of DMF were stirred at room temperature for 1h, then a solution of 1- (4- (2-bromoethoxy) phenyl) -5- (2-thiophene) -1, 4-pentadien-3-one (intermediate 4) in DMF was added slowly and stirring was continued at room temperature for 6-8 h. The reaction was followed by TLC, and when the reaction was completed, the reaction was stopped, the reaction mixture was dispersed in 100mL of water, extracted with ethyl acetate (3X 25mL), and combinedAnd the organic layer was washed with saturated brine (3 × 40mL), dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure to give a crude product, which was purified by column chromatography (ethyl acetate: methanol ═ 1: 3, V/V) to give the desired compound in the following yield: 44 percent.
Example 2
(1E, 4E) -1- (2- (2- ((5, 6-diphenyl-1, 2, 4-triazine-3-mercaptoethoxy) phenyl) -5- (4-chlorophenyl) -1, 4-pentadien-3-one (target Compound A2):
Figure BSA0000183806020000121
the procedure was analogous to that of example 1, selecting the corresponding starting material to prepare the title compound a2, yield: 56 percent.
Example 3
(1E, 4E) -1- (2- (2- ((5, 6-diphenyl-1, 2, 4-triazine-3-mercaptoethoxy) phenyl) -5- (4-nitrophenyl) -1, 4-pentadien-3-one (target Compound A3):
Figure BSA0000183806020000122
the procedure was analogous to that of example 1, selecting the corresponding starting material to prepare the title compound a3, yield: 35 percent.
Example 4
(1E, 4E) -1- (4-chlorophenyl) -5- (4- (2- ((5, 6-diphenyl-1, 2, 4-triazine-3-mercaptoethoxy) -3-methoxyphenyl) -1, 4-pentadien-3-one (target Compound A4):
Figure BSA0000183806020000131
the procedure was analogous to that of example 1, selecting the corresponding starting material to prepare the title compound a4, yield: 46 percent.
Example 5
(1E, 4E) -1- (4- (2- ((5, 6-diphenyl-1, 2, 4-triazine-3-mercaptoethoxy) phenyl) -5- (3, 4-dimethoxy) -1, 4-pentadien-3-one (title compound A5):
Figure BSA0000183806020000132
the procedure was analogous to that of example 1, selecting the corresponding starting material to prepare the title compound a5, yield: 44 percent.
Example 6
(1E, 4E) -1- (4- (2- ((5, 6-diphenyl-1, 2, 4-triazine-3-mercaptoethoxy) phenyl) -5- (4-nitrophenyl) -1, 4-pentadien-3-one (target Compound A6):
Figure BSA0000183806020000133
the procedure was analogous to example 1, selecting the corresponding starting material to prepare the title compound, title compound a6, in yield: 34 percent.
Example 7
(1E, 4E) -1- (4-methoxyphenyl) -5- (4- (2- ((5, 6-diphenyl-1, 2, 4-triazin-3-mercaptoethoxy) -3-methoxyphenyl) -1, 4-pentadien-3-one (target Compound A7):
Figure BSA0000183806020000134
the procedure was analogous to that of example 1, selecting the corresponding starting material to prepare the title compound a7, yield: 56 percent.
Example 8
(1E, 4E) -1- (2, 4-dimethoxyphenyl) -5- (4- (2- ((5, 6-diphenyl-1, 2, 4-triazin-3-mercaptoethoxy) -3-methoxyphenyl) -1, 4-pentadien-3-one (target Compound A8):
Figure BSA0000183806020000141
the procedure was analogous to that of example 1, selecting the corresponding starting material to prepare the title compound A8, yield: 62 percent.
Example 9
(1E, 4E) -1- (4- (2- ((5, 6-dimethyl-1, 2, 4-triazine-3-mercaptoethoxy) phenyl) -5- (2-thiophene) -1, 4-pentadien-3-one (target Compound A9):
Figure BSA0000183806020000142
preparation of the title compound a9) in analogy to the procedure of example 1, selecting the corresponding starting material, yield: 58 percent.
Example 10
(1E, 4E) -1- (4- (2- ((5, 6-diphenyl-1, 2, 4-triazine-3-mercaptoethoxy) phenyl) -5- (4-chlorophenyl) -1, 4-pentadien-3-one (target Compound A10):
Figure BSA0000183806020000143
the procedure was analogous to that of example 1, selecting the corresponding starting material to prepare the title compound a10, yield: 44 percent.
Example 11
(1E, 4E) -1- (4- (2- ((5, 6-diphenyl-1, 2, 4-triazine-3-mercaptoethoxy) phenyl) -5- (2-chlorophenyl) -1, 4-pentadien-3-one (target Compound A11):
Figure BSA0000183806020000144
the procedure was analogous to example 1, selecting the corresponding starting material to prepare the title compound a11 in 54% yield.
Example 12
(1E, 4E) -1- (2- (2- ((5, 6-diphenyl-1, 2, 4-triazine-3-mercaptoethoxy) phenyl) -5- (3, 4-dimethoxyphenyl) -1, 4-pentadien-3-one (target Compound A12):
Figure BSA0000183806020000145
preparation of the title compound a12) in analogy to the procedure of example 1, selecting the corresponding starting material, yield: 36 percent.
Example 13
(1E, 4E) -1- (2- (2- ((5, 6-diphenyl-1, 2, 4-triazine-3-mercaptoethoxy) phenyl) -5- (2-pyridine) -1, 4-pentadien-3-one (target Compound A13):
Figure BSA0000183806020000151
the procedure was analogous to that of example 1, selecting the corresponding starting material to prepare the title compound a13, yield: 46 percent.
Example 14
(1E, 4E) -1- (2- (2- ((5, 6-diphenyl-1, 2, 4-triazine-3-mercaptoethoxy) phenyl) -5- (3-methylphenyl) -1, 4-pentadien-3-one (target Compound A14):
Figure BSA0000183806020000152
the procedure was analogous to that of example 1, selecting the corresponding starting material to prepare the title compound a14, yield: 38 percent.
Example 15
(1E, 4E) -1- (2- (2- ((5, 6-diphenyl-1, 2, 4-triazine-3-mercaptoethoxy) phenyl) -5- (2-fluorophenyl) -1, 4-pentadien-3-one (target Compound A15):
Figure BSA0000183806020000153
the procedure was analogous to that of example 1, selecting the corresponding starting material to prepare the title compound a15, yield: 41 percent.
Example 16
(1E, 4E) -1- (2- (2- ((5, 6-diphenyl-1, 2, 4-triazine-3-mercaptoethoxy) phenyl) -5- (2-furan) -1, 4-pentadien-3-one (target Compound A16):
Figure BSA0000183806020000154
the procedure was analogous to that of example 1, selecting the corresponding starting material to prepare the title compound a16, yield: 61 percent.
Example 17
(1E, 4E) -1- (2- (2- ((5, 6-diphenyl-1, 2, 4-triazine-3-mercaptoethoxy) phenyl) -5- (4-bromophenyl) -1, 4-pentadien-3-one (target Compound A17):
Figure BSA0000183806020000161
the procedure was analogous to that of example 1, selecting the corresponding starting material to prepare the title compound a17, yield: 60 percent.
The physical and chemical properties of the synthesized triazine-containing 1, 4-pentadiene-3-one derivatives are shown in Table 1, and the nuclear magnetic resonance hydrogen spectrum (1H NMR) and carbon Spectroscopy (13C NMR) data are shown in table 2.
TABLE 1 physicochemical Properties of the target Compounds obtained in examples 1 to 17
Figure BSA0000183806020000162
Figure BSA0000183806020000171
TABLE 2 NMR data on hydrogen and carbon spectra of the objective Compounds obtained in examples 1 to 17
Figure BSA0000183806020000172
Figure BSA0000183806020000181
Figure BSA0000183806020000191
Figure BSA0000183806020000201
Activity test example 1: anti-plant bacterial activity test:
(1) test method
The in vitro inhibitory activity of the target compound on ralstonia solanacearum, rice bacterial leaf blight and citrus canker pathogen is tested by a turbidity method at the concentrations of 100 and 50 mu g/mL, and the contrast agent in the experiment is thiediazole copper. Culturing ralstonia solanacearum, rice bacterial leaf blight and citrus ulcer on an NA solid culture medium, and then culturing in a constant-temperature bacterial incubator at 28 ℃ until single colony grows out. Selecting a proper amount of central yellow single colony, placing the single colony in an NB liquid culture medium, and carrying out shake culture in a constant temperature shaking table at 28 ℃ and 180r/min until the single colony reaches the logarithmic growth phase for later use. The compound and the contrast agent are prepared into concentrations of 100 and 50 mu g/mL, 1mL of the compound and the contrast agent are added into a test tube filled with 4mL of NB liquid medium, 40 mu L of the NB liquid medium containing ralstonia solanacearum, rice bacterial leaf blight and citrus canker is added into the test tube, and shaking culture is carried out on the test tube at the constant temperature of 28 ℃ and 180r/min for 48 h. Measuring OD of sterilized NB liquid medium at 595nm wavelength in spectrophotometer595The OD of the bacterial suspension was measured simultaneously at each concentration595The value is obtained.
Correcting OD595Value-bacteria-containing Medium OD595Sterile Medium OD595
Inhibition ratio (%) (control medium OD after correction)595Corrected drug-containing Medium OD595) Corrected OD value of control medium liquid is multiplied by 100%.
(2) Test results of biological activity against plant pathogens
TABLE 3 bacteriostatic activity (% inhibition) of examples 1-17a
Figure BSA0000183806020000202
aAverage three replicates;bthiodiazole copper (20% wettable powder) was used as a positive control.
The inhibition activity of the target compound on pseudomonas solanacearum, fusarium oxysporum kuhn and citrus canker pathogen is tested by a turbidity method by taking commercial medicament thiabendazole copper as a positive control at the test concentration of 100 and 50 mu g/mL (see table 3). The results show that: all the compounds have certain inhibitory activity on ralstonia solanacearum, rice bacterial leaf blight and citrus canker. For ralstonia solanacearum, the inhibition rates of the compound A1 (58.2%), A2 (53.9%), A9 (53.5%) and A10 (61.9%) at 100 mu g/mL exceed that of thiediazole copper (50.1%); for rice bacterial blight, the inhibition rates of the compound A5 (54.6%), A8 (55.6%), A13 (60.5%) and A15 (56.5%) at 100 μ g/mL exceeded that of thiediazole copper (49.7%); for citrus canker pathogen, the inhibition rates of compound A10 (91.8%), A11 (95.4%) and A16 (74.6%) were all greater than that of Thiobacillus copper (70.5%) at 100. mu.g/mL.
Activity test example 2: anti-tobacco mosaic virus activity test:
test method
A. Purification of viruses
A Zhoxueping method (Zhou, X.P.; Xu, Z.X.; Xu, J.; Li, D.B.J.south Chin.Agric.Univ.1995, 16, 74-79.) is adopted, and the upper leaves of the host Nicotiana tabacum.L plant are selected and inoculated for more than 3 weeks, a TMV system infects the upper leaves of the host Nicotiana tabacum.L plant, the upper leaves are homogenized in a phosphate buffer solution, the upper leaves are filtered by a double-layer gauze, the upper leaves are centrifuged at 8000r, the upper leaves are treated by 2 times of polyethylene glycol, the upper leaves are centrifuged, and the precipitate is suspended by the phosphate buffer solution to obtain a refined extraction liquid of the TMV. The whole experiment was carried out at 4 ℃. And measuring the absorbance value of the 260nm wavelength by using an ultraviolet spectrophotometer, and calculating the virus concentration according to a formula.
Concentration of virus (mg/mL) ═ A260 Xdilution factor/E0.1% 1cm260nm
Wherein E represents the extinction coefficient, i.e. the light absorption at a wavelength of 260nm for a suspension having a concentration of 0.1% (1mg/mL) at an optical path length of 1 cm. E0.1% of TMV 1cm260nm is 5.0.
B. In vivo therapeutic effect of agents on TMV infection
In vivo treatment of infections with agents: selecting folium Xinliangye of 5-6 leaf stage with consistent growth, topping, spreading emery to the whole leaf, dipping virus juice (6 × 10) with a row pen-3mg/mL) whole leaf virus, air-dried naturally and washed with clear water. After the leaves are dry, lightly applying the medicament on the left half leaf by using a writing brush, applying a solvent with the concentration corresponding to the solvent on the right half leaf as a control, recording the number of the dead spots after 6-7 days, and calculating the inhibition rate according to the following formula.
C. In vivo protection of agents against TMV infection
In vivo protection of agents against TMV infection: selecting the heart-leaf tobacco with consistent growth and 5-6 leaf stage, topping, lightly applying the medicament on the left half leaf with a writing brush, and applying the solvent with the concentration corresponding to the solvent on the right half leaf as a control. Spreading emery powder to the whole leaf after 24 hr, and dipping virus juice (6 × 10) with a row pen-3mg/mL) of the whole leaf was inoculated with the virus, washed with clear water, and after 6-7 days, the number of dead spots was recorded, and the inhibition rate was calculated according to the following formula.
D. In vivo inactivation of TMV infection by agents
Mixing the medicament and virus juice with the same volume, inactivating for 30min, dipping the mixed solution of the medicament and virus with a row pen, manually rubbing and inoculating on the left half of the leaf scattered with carborundum, and supporting the lower part of the leaf with a flat wood plate. Sterile water is mixed with the viral juice to inoculate the right half leaf. 3 plants are set for each medicament treatment, each plant has 5-6 leaves, then the plants are put into a light incubator for moisture preservation and culture, the temperature is controlled to be 23 +/-1 ℃, after the light is 10000Lux, the number of the generated scorched spots is observed and recorded after 6-7d, and the inhibition rate is calculated according to the following formula.
Inhibition rate (average number of dead spots in half-leaf without drug application-number of dead spots in half-leaf with drug application)/average number of dead spots in half-leaf without drug application × 100%
Wherein the average number of half-leaf dry spots without the application of the medicament and the average number of half-leaf dry spots with the application of the medicament are the average of three times of repetition of each group.
Results of biological activity test for resisting tobacco mosaic virus
TABLE 4 example of Compound A1-17 against tobacco mosaic VirusTherapeutic, protective and inactivating activitya
Figure BSA0000183806020000221
aAverage three replicates;bningnanmycin was used as a positive control.
The therapeutic activity, protective activity and inactivating activity of the target compound A1-A17 against Tobacco Mosaic Virus (TMV) were tested at a test concentration of 500. mu.g/mL using the semileaf cumic method with the commercial agent ningnanmycin as a control (see Table 4). The test results show that: most of the target compounds have certain therapeutic, protective and inactivating activity against TMV. The target compounds A6, A10 and A11 have good therapeutic effect on TMV, and the inhibition rates of the target compounds A6, A10 and A11 are 53.8%, 66.3 and 59.9% respectively, and exceed 45.7% of ningnanmycin; the target compounds A2, A4 and A7 have better protection effect on TMV, and the inhibition rates are respectively 54.5%, 53.9% and 61.4%, which are better than that of ningnanmycin (53.4%); the target compounds A1 and A4 have certain inactivation effect on TMV, and the inhibition rates are 66.2 and 63.6 percent and are close to Ningnanmycin (77.3 percent).
The experimental activity data show that the triazine-containing 1, 4-pentadiene-3-ketone derivative has a certain inhibition effect on plant viruses (TMV) and plant germs (ralstonia solanacearum, rice shutter blight and citrus canker germs), wherein part of target compounds have excellent activity on resisting the plant viruses and inhibiting the plant germs, can be used as potential plant virus resisting and bacteriostatic medicaments, and have good application prospects.
In summary, the present invention is only a preferred embodiment, and is not limited to any form, and any simple modification, equivalent change and modification made to the above embodiment according to the technical essence of the present invention are within the scope of the technical solution of the present invention without departing from the technical solution of the present invention.

Claims (5)

1. 1, 4-pentadien-3-one compounds containing triazine, characterized in that the compounds are independently selected from the following specific compounds:
Figure FSB0000197595660000011
Figure FSB0000197595660000021
2. a composition characterized by comprising a compound of claim 1, and an agriculturally acceptable adjuvant or fungicide, insecticide, or herbicide; the formulation of the composition is selected from missible oil, powder, granules, aqueous solution, suspending agent, ultra-low volume spraying agent, microcapsule, smoke agent and aqueous emulsion.
3. Use of the compound according to claim 1, or the composition according to claim 2 for controlling agricultural diseases such as bacterial blight of rice, bacterial wilt of tobacco, mosaic disease of tobacco, and canker of citrus.
4. A method for controlling agricultural pests is characterized in that: allowing the compound of claim 1, or the composition of claim 2, to act on the pest or its living environment; the harmful substances are rice bacterial leaf blight, tobacco bacterial wilt, tobacco mosaic disease and citrus canker.
5. A method for protecting a plant from an agricultural pest comprising the method step wherein the plant is contacted with a compound of claim 1, or a composition of claim 2.
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