CN114380815A - Phytoalexin derivative and preparation method and application thereof - Google Patents

Phytoalexin derivative and preparation method and application thereof Download PDF

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CN114380815A
CN114380815A CN202210065421.7A CN202210065421A CN114380815A CN 114380815 A CN114380815 A CN 114380815A CN 202210065421 A CN202210065421 A CN 202210065421A CN 114380815 A CN114380815 A CN 114380815A
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bromo
thiazole
carbohydrazide
indol
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CN114380815B (en
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卢爱党
李林
王兹稳
廖安财
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Hebei University of Technology
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • 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
    • A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
    • A01N43/74—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms five-membered rings with one nitrogen atom and either one oxygen atom or one sulfur atom in positions 1,3
    • A01N43/78—1,3-Thiazoles; Hydrogenated 1,3-thiazoles
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    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
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Abstract

The invention relates to a phytoalexin derivative and a preparation method and application thereof. The structural general formula of the calalexin derivative of the phytoalexin is shown as I, the derivative introduces a new substituent group on the basis of alkaloid calalexin, a bromine atom is introduced into a 5-position in a core skeleton indole structural unit of a natural product calalexin, and a hydrazide hydrazone functional group is introduced into a 4-position in a thiazole structural unit, so that a series of calalexin derivatives are generated. The alkaloid calalexin derivative has good plant virus resisting activity and broad-spectrum plant pathogenic bacteria killing activity.

Description

Phytoalexin derivative and preparation method and application thereof
Technical Field
The invention belongs to the technical field of fine chemicals, and particularly relates to a phytoalexin derivative, and a preparation method and an agricultural application thereof as a biocide.
Background
Camalexin (3-thiazol-2' -yl-indole, shown as a structural formula I) is a plant protector specific to crucifers, also called camelina sativa, which is a sulfur-containing indole alkaloid, and representative phytoalexins or plant protectors generated by crucifers after being stimulated by the outside world can be induced by various pathogens (such as bacteria, fungi, viruses, oomycetes and the like) [ Glawischnig, E.Camalexin.phytochem.2007,68(4), 401-.
Figure BDA0003477269440000011
Since 1991 brown et al [ brown, L.M; conn, K.L; ayer, W.A; from the first separation of phytoalexin from leaves of camellia japonica, Tewari, j.p. tetrahedron 1991,47(24), 3909-; taga, c.; ozawa, m.; sanada, n.; kizu, R.J.Nat.Med.2022,76, 110-118; mezenev, r.; mojzis, j.; pilatova, m.; kutschy, P.Neoplama 2003,50, 239-; pilatova, m.; ivanova, l.; kutschy, p.; varinska, l.; saxunova, l.; reovska, M.; sarissky, m.; seliga, r.; mirossay, l.; mojzis, J.Toxicol.Vitr.2013,27, 939-; mezenev, r.; updegrove, t.; kutschy, p.; reovska, M.; mcdonald, j.f.j.nat.med.2011,65, 488-499; mezenev, r.; galitzi, m.; kutschy, p.; docampo, r.exp parasitol.2009,122, 66-69; pedras, m.s.c.; ahiahounu, P.W.K.Bioorgan.Med.chem.2002,10, 3307-one 3312 ]. Literature [ Ayer, W.A; craw, p.a; ma, Y.T; miao, S.C. tetrahedron 1992,48(14), 2919-2924 ] uses corresponding indole and 2-bromothiazole as raw materials to obtain alkaloid camalexin and derivatives (shown as a reaction formula I) through a Grignard reaction, and finds that the compounds have certain bactericidal activity on amygdalus sp (Cladosporium sp.) and a very flammable reagent, namely magnesium methyl iodide, is required in the reaction process.
Figure BDA0003477269440000012
Literature [ Pedras, m.s.c.; minic, Z.; Sarma-Maxilapalle, V.K.J.Agric.food chem.2009,57, 2429-2435 ] synthesizes a series of derivatives (such as a structural formula II) containing a calalexin core structure, and investigates the inhibitory activity of the derivatives on Brassica oxidase (a fungal detoxification enzyme capable of overcoming the plant defense effect), finds that the synthesized series of compounds have certain inhibitory activity on Leptosphaeria maculans (Leptosphaeria maculans), but the calalexin derivative 2f has no inhibitory effect on the Brassica oxidase; the application of resisting phytopathogens is also only limited to the alternaria cucumerina.
Figure BDA0003477269440000021
Literature [ Pedras, m.s.c.; abdoli, A.Bioorg.Med.chem.2013, 214541-4549. ] to explore the biotransformation process of the phytoalexin, the reported method was used to synthesize the phytoalexin and derivatives 2b, 2f, and other substituents were introduced into the thiazole structure by the method such as reaction formula two to prepare compounds 2 g-2 j; the study of the biological activity of Alte rnaria brassicola shows that: when the dosage is 0.2mM, the inhibition rates of calalexin and the compound 2b and 2 g-2 h on the alternaria brassicae are both 100%, but the inhibition rate of 2f on the alternaria brassicae is 71%, and the inhibition rates of 2 i-2 j on the alternaria brassicae are 38% and 41%, respectively; the substituent of the thiazole structural unit has a remarkable influence on the inhibitory activity of the alternaria brassicae, but unfortunately, only specific functional groups (such as methyl, carboxylic acid and hydroxymethyl) can be introduced into the thiazole structural unit due to the limitation of the type of the halide, and the regulation of the biological activity and the compound property of the thiazole structural unit cannot be realized.
Figure BDA0003477269440000022
Literature [ Guo, j.; hao, y.; ji, x.; wang, z.; liu, y.; ma, d.; li, Y.; pang, H.; ni, j.; wang, Q.J.Agric.food chem.2019,67,10018-10031. and patent [ CN109418267B ] report the application of nortopsentin alkaloid derivatives containing bis-indole and thiazole structural units in the system in the control of plant diseases and insect pests, the synthetic method is shown in the reaction formula II, and the biological activity research shows that: most of nortopsentin alkaloid derivatives containing double indole and thiazole structural units have the inhibition rate on tobacco mosaic virus better than commercial varieties of ribavirin, and have certain bactericidal activity on 14 common plant pathogenic bacteria (tomato early blight, wheat scab, rice blast, phytophthora capsici leonian, rape sclerotium, rice sheath blight, cucumber gray mold, cucumber fusarium wilt, peanut brown spot, apple ring rot, wheat sheath blight, corn speckles, watermelon anthracnose and rice bakanae). Although the nortopsentiin alkaloid derivative containing the bisindole and thiazole structural units has good activity of resisting tobacco mosaic virus and bactericidal activity, 2-bromo-1- (1H-indol-3-yl) ethan-1-one used in the reaction process cannot be directly purchased and at least 3 steps of reaction are needed for synthesis, so when an indole group is introduced into the 4-position of the thiazole, the influence of the substituent on the biological activity is limited, and the regulation and control capability on the biological activity and the property of the compound is relatively weak.
Figure BDA0003477269440000031
Disclosure of Invention
The invention aims to provide a plant protection element calalexin derivative, a preparation method and application thereof, aiming at the problems that the plant protection element calalexin derivative has the advantages of diverse activity, good environmental compatibility and the like and has relatively low activity. The derivative introduces a new substituent group on the basis of an alkaloid camalexin, introduces a bromine atom at the 5-position in a core skeleton indole structural unit of a natural product camalexin and introduces a hydrazide hydrazone functional group at the 4-position in a thiazole structural unit to generate a series of camalexin derivatives. The alkaloid calalexin derivative has good plant virus resisting activity and broad-spectrum plant pathogenic bacteria killing activity.
The technical scheme adopted by the invention for solving the technical problem is as follows:
a plant protection element calalexin derivative, the structural general formula of the plant protection element calalexin derivative is shown as I,
Figure BDA0003477269440000032
wherein R is phenyl, 2-fluorophenyl, 3, 4-difluorophenyl, 2, 6-difluorophenyl, 2, 4-difluorophenyl, 2, 3-difluorophenyl, 4-fluorophenyl, 2-chlorophenyl, 3, 4-dichlorophenyl, 2, 6-dichlorophenyl, 2, 4-dichlorophenyl, 2, 3-dichlorophenyl, 2, 5-dichlorophenyl, 4-chlorophenyl, 5-chloro-2-fluorophenyl, 2-bromophenyl, 3-bromophenyl, 4-iodophenyl, 2-nitrophenyl, 3-nitrophenyl, 4-nitrophenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 2-trifluoromethylphenyl, 3-trifluoromethylphenyl, 4-trifluoromethylphenyl, 3, 5-bis (trifluoromethyl) phenyl, 3-methoxyphenyl, 3,4, 5-tris (methoxy) phenyl, 4-methoxyphenyl, 2-thienyl, 2-furyl, 2-pyridyl, 4-pyridyl, 1-naphthyl, 4-quinolyl, cyclohexyl, cyclopentyl, ethyl, n-propyl, isopropyl, n-butyl, n-pentyl, n-hexyl, n-heptyl, n-octyl or benzyl.
The said plant-protecting agent calalexin derivative is preferably:
Figure BDA0003477269440000041
wherein, the compound shown in the chemical structural formula I-1 is (E) -N ' -benzylidene-2- (5-bromo-1H-indol-3-yl) thiazole-4-carbohydrazide, the compound shown in the chemical structural formula I-2 is (E) -2- (5-bromo-1H-indol-3-yl) -N ' - (4-methoxybenzylidene) thiazole-4-carbohydrazide, the compound shown in the chemical structural formula I-3 is (E) -2- (5-bromo-1H-indol-3-yl) -N ' - (3,4, 5-trimethoxybenzylidene) thiazole-4-carbohydrazide, the compound shown in the chemical structural formula I-4 is (E) -2- (5-bromo-1H-indol-3-yl) -N '- (4-trifluoromethyl benzylidene) thiazole-4-carbohydrazide, the compound shown in the chemical structural formula I-5 is (E) -2- (5-bromo-1H-indol-3-yl) -N' - (4-fluorobenzylidene) thiazole-4-carbohydrazide, the compound shown in the chemical structural formula I-6 is (E) -2- (5-bromo-1H-indol-3-yl) -N '- (2-bromobenzylidene) thiazole-4-carbohydrazide, and the compound shown in the chemical structural formula I-7 is (E) -2- (5-bromo-1H-indol-3-yl) -N' - (2-bromobenzylidene) thiazole-4-carbohydrazide -1H-indol-3-yl) -N '- (4-nitrobenzylidene) thiazole-4-carbohydrazide which is represented by the chemical structural formula I-8 and is 2- (5-bromo-1H-indol-3-yl) -N' - (naphthalen-1-ylmethylene) thiazole-4-carbohydrazide, which is represented by the chemical structural formula I-9 and is (E) -2- (5-bromo-1H-indol-3-yl) -N '- (pyridin-4-ylmethylene) thiazole-4-carbohydrazide, which is represented by the chemical structural formula I-10 and is (E) -2- (5-bromo-1H-indol-3-yl) -N' - (quinoline-4- Methylene) thiazole-4-carbohydrazide, wherein the compound shown in the chemical structural formula I-11 is 2- (5-bromo-1H-indol-3-yl) -N ' - (furan-2-ylmethylene) thiazole-4-carbohydrazide, the compound shown in the chemical structural formula I-12 is E) -2- (5-bromo-1H-indol-3-yl) -N ' - (cyclohexylmethylene) thiazole-4-carbohydrazide, the compound shown in the chemical structural formula I-13 is (E) -2- (5-bromo-1H-indol-3-yl) -N ' - (2-methylpropylidene) thiazole-4-carbohydrazide, the compound shown in the chemical structural formula I-14 is (E) -2- (5-bromo-1H-indol-3-yl) -N '-butylidene thiazole-4-carbohydrazide, and the compound shown in the chemical structural formula Ia-15 is (E) -2- (5-bromo-1H-indol-3-yl) -N' -octylidene thiazole-4-carbohydrazide.
The preparation method of the calalexin derivative comprises the following steps:
(1) taking 5-bromo-1H-indole-3-thiocarboxamide (3e) as a raw material, and heating and refluxing the raw material and 3-bromoethyl pyruvate in an ethanol solvent to react to obtain a compound 5;
wherein, the mol ratio is that 5-bromine-1H-indole-3-thiocarboxamide: ethyl 3-bromopyruvate ═ 1: 1-1.5, adding 5-20 mL of ethanol into 5-bromo-1H-indole-3-thiocarboxamide per millimole, wherein the reaction time is 1-4H and the temperature is 75-85 ℃;
(2) taking a compound 5 and 80% hydrazine hydrate as raw materials, and heating and refluxing the raw materials in an ethanol solvent to react to obtain a compound 6;
wherein, the molar ratio is that the compound 5: hydrazine hydrate 1: 3-10, adding 15-30 mL of ethanol into each millimole of compound 5, wherein the reaction time is 1-4 h, and the temperature range is 75-85 ℃;
(3) a method for preparing compounds I-1 to I-15 comprises the following steps:
taking a compound 6 and an aldehyde compound as raw materials, and heating and refluxing the raw materials in an ethanol solvent to obtain compounds I-1 to I-15;
wherein, the molar ratio is that compound 6: aldehyde compound is 1: 1-2, adding 15-30 mL of ethanol into each millimole of compound 6, wherein the reaction time is 1-4 h, and the temperature range is 75-85 ℃;
the aldehyde compound is benzaldehyde, 2-fluorobenzaldehyde, 3, 4-difluorobenzaldehyde, 2, 6-difluorobenzaldehyde, 2, 4-difluorobenzaldehyde, 2, 3-difluorobenzaldehyde, 4-fluorobenzaldehyde, 2-chlorobenzaldehyde, 3, 4-dichlorobenzaldehyde, 2, 6-dichlorobenzaldehyde, 2, 4-dichlorobenzaldehyde, 2, 3-dichlorobenzaldehyde, 2, 5-dichlorobenzaldehyde, 4-chlorobenzaldehyde, 5-chloro-2-fluorobenzaldehyde, 2-bromobenzaldehyde, 3-bromobenzaldehyde, 4-iodobenzaldehyde, 2-nitrobenzaldehyde, 3-nitrobenzaldehyde, 4-nitrobenzaldehyde, 3-nitrobenzaldehyde, or mixture of benzaldehyde, 2-methylbenzaldehyde, 3-methylbenzaldehyde, 4-methylbenzaldehyde, 2-trifluoromethylbenzaldehyde, 3-trifluoromethylbenzaldehyde, 4-trifluoromethylbenzaldehyde, 3, 5-bis (trifluoromethyl) benzaldehyde, 3-methoxybenzaldehyde, 3,4, 5-tris (methoxy) benzaldehyde, 4-methoxybenzaldehyde, 2-thiophenecarboxaldehyde, 2-furancarbaldehyde, 2-pyridinecarboxaldehyde, 4-pyridinecarboxaldehyde, 1-naphthaldehyde, 4-quinolinecarboxaldehyde, cyclohexylcyclohexanecarboxaldehyde, cyclopentylcyclohexanecarboxaldehyde, n-propionaldehyde, n-butyl, isobutyl, n-valeraldehyde, n-hexanal, n-heptanal, n-octanal, n-nonanal or phenylacetaldehyde.
The application of the plant protection element calalexin derivative is used as an anti-plant virus agent, and the plant protection element calalexin derivative is a compound shown in the following chemical structural formulas I-1-I-15:
Figure BDA0003477269440000051
the plant protector camalexin derivatives I-1-I-15 are used as plant virus resisting agents, wherein the plant virus is tobacco mosaic virus, pepper virus, rice virus, tomato virus, sweet potato virus, melon virus or corn dwarf mosaic virus. Wherein, the compound has excellent activity for resisting tobacco mosaic virus, the activity of most compounds is obviously superior to that of commercial varieties of ribavirin, and the activity of the compounds I-1 to I-2, I-4 to I-13 and I-15 is obviously superior to that of phytoalexin.
The invention relates to application of plant protecting element calalexin derivatives I-1-I-15 in the aspect of resisting plant pathogenic bacteria, in particular to application of the plant pathogenic bacteria in the aspects of tomato early blight, wheat scab, rice blast, phytophthora capsici, rape sclerotium, rice sheath blight, cucumber gray mold, cucumber fusarium wilt, peanut brown spot, apple ring rot, wheat sheath blight, corn small spot, watermelon anthrax or rice bakanae seedling; shows broad-spectrum anti-plant pathogenic bacteria activity, shows a different biological activity spectrum with the phytoalexin, and achieves unexpected effects and breakthrough progress.
Compared with the prior art, the invention has the prominent substantive characteristics and remarkable progress as follows:
(1) the fact that the calalexin derivative of the phytoalexin has good anti-plant virus activity is found for the first time, under the same test condition, when the dosage is 500 mu g/mL, I-1-I-2, I-4-I-13 and I-15 are all superior to commercial varieties of ribavirin, and compounds I-6 and I-8 show anti-TMV activity equivalent to or higher than that of ningnanmycin when the dosage is 500 mu g/mL; in addition, the plant protectant camalexin derivative has broad-spectrum inhibitory activity on 14 common agricultural pathogens, for example, the inhibition rates of the compounds I-1 and I-13 for resisting phytophthora capsici, rhizoctonia solani and sclerotinia sclerotiorum are obviously superior to that of camalexin, the compounds I-12 for resisting rice blast fungus and cucumber botrytis are obviously superior to that of camalexin, and unexpected effects and breakthrough progress are achieved; the invention expands the application range of the plant protection element calalexin derivative as the biological pesticide.
(2) The important intermediate 2- (5-bromo-1H-indole 3-yl) thiazole-4-carbohydrazide (6) is obtained in the preparation process of the calalexin derivative of the phytoalexin, and the compound can be heated and refluxed with various aldehyde compounds of different types in an ethanol solution to obtain different substituted calalexin derivatives, thereby providing guarantees for system exploration of structure-activity relationship, regulation and control of biological activity, regulation of compound solubility and stability and the like.
Detailed Description
The preparation method of the calalexin derivative comprises the following specific steps:
Figure BDA0003477269440000061
taking 5-bromo-1H-indole-3-thiocarboxamide shown in chemical structural formula 3e as a raw material, heating and refluxing the raw material and 3-bromoethyl pyruvate in an ethanol solvent to react to generate a 2- (5-bromo-1H-indole-3-yl) thiazole-4-ethyl formate intermediate shown in chemical structural formula 5; dissolving the intermediate product in ethanol, adding 80% hydrazine hydrate, and performing hydrazinolysis reaction under heating condition to obtain important intermediate 2- (5-bromo-1H-indole 3-yl) thiazole-4-carbohydrazide shown in chemical structural formula 6; finally, 2- (5-bromo-1H-indole-3-yl) thiazole-4-carbohydrazide reacts with different substituted aldehyde compounds to prepare the 2- (5-bromo-1H-indole-3-yl) -N' -methylene thiazole-4-carbohydrazide shown in the general formula I.
The preparation of compounds I-1 to I-5 is as follows:
example 1
Figure BDA0003477269440000062
The preparation method of (E) -N' -benzylidene-2- (5-bromo-1H-indol-3-yl) thiazole-4-carbohydrazide shown in the chemical structural formula I-1 comprises the following steps:
firstly, under the protection of nitrogen at 50 ℃ below zero, chlorosulfonic acid isocyanate (12mmol) is dropwise added into a DMF (10mL) solution of 5-bromoindole (10mmol), and after the dropwise addition is finished, the temperature is raised to room temperature for continuous reaction for 1.5 hours. After TLC detection reaction is finished, pouring the reaction system into ice water, stirring for 30 minutes, and performing suction filtration to obtain a yellow solid 5-bromo-1H-indole-3-carbonitrile with the yield of 99%; the melting point is 185-186 ℃;1H NMR(400MHz,CDCl3)δ9.18(s,1H),7.93(s,1H),7.76(s,1H),7.45(d,J＝8.7Hz,1H),7.39(d,J＝8.7Hz,1H)；13C NMR(100MHz,DMSO-d6) Delta 135.9,134.0,128.4,126.1,120.7,115.6,115.0,114.4,84.0, and the product was determined to be 5-bromo-1H-indole-3-carbonitrile.
Second, 5-bromo-1H-indole-3-carbonitrile (8mmol) was added to 70% sulfur in 10mL DMFStirring a mixed solution of a sodium hydride solution (24mmol) and magnesium chloride hexahydrate (8mmol) for 12 hours at 40 ℃, then pouring a mixed system into 200 ml of water, filtering, adding a filter cake into a 1M HCl solution, stirring for 20 minutes, filtering, washing the filter cake with water to obtain a white solid 5-bromo-1H-indole-3-thiocarbamide, wherein the yield is 89%, and the melting point is 145-147 ℃;1H NMR(400MHz,DMSO-d6)δ12.00(s,1H),9.05(s,1H),8.95(s,1H),8.91(s,1H),8.15(s,1H),7.43(d,J＝8.5Hz,1H),7.30(d,J＝8.5Hz,1H)；13C NMR(100MHz,DMSO-d6) δ 193.5,136.0,129.2,128.5,125.1,124.6,116.0,114.5,114.2, determining the product to be 5-bromo-1H-indole-3-thiocarboxamide; wherein the first and second step references [ Guo, j.c.; hao, y.n.; ji, x.f.; wang, z.w.; liu, y.x.; ma, d.j.; li, y.q.; pang, h.l.; ni, j.p.; wang, Q.M.J.Agric.food chem.2019,67,10018-10031.]The preparation method is carried out.
Step three, adding 5-bromo-1H-indole-3-thiocarboxamide (2mmol) into an ethanol (20mL) solution of ethyl 3-bromopyruvate (2mmol), heating at 80 ℃ for 2 hours, and performing suction filtration to obtain a yellow solid ethyl 2- (5-bromo-1H-indol-3-yl) thiazole-4-carboxylate with the yield of 98%; melting point 202-203 ℃;1H NMR(400MHz,DMSO-d6)δ12.07(s,1H),8.42(d,J＝1.8Hz,1H),8.38(s,1H),8.27(d,J＝2.9Hz,1H),7.49(d,J＝8.6Hz,1H),7.37(d,J＝8.6Hz,1H),4.35(q,J＝7.1Hz,2H),1.35(t,J＝7.1Hz,3H)；13C NMR(100MHz,DMSO-d6)δ162.9,160.8,146.0,135.3,128.9,125.8,125.2,122.6,114.3,113.5,109.4,60.7,14.2.C14H12BrN2O2S[M+H]+350.9797,found(ESI+)350.9794, the product was determined to be ethyl 2- (5-bromo-1H-indol-3-yl) thiazole-4-carboxylate.
Step four, dissolving the compound ethyl 2- (5-bromo-1H-indol-3-yl) thiazole-4-carboxylate (1mmol,1.0equiv.) and hydrazine hydrate (80%, 0.2mL,5mmol,5equiv.) in ethanol (20mL), heating to react at the temperature of 80 ℃ for 2 hours, cooling to room temperature, and performing suction filtration to obtain yellow solid 2- (5-bromo-1H-indol-3-yl) thiazole-4-carbohydrazide with the yield of 69%; the melting point is 295-296 ℃;1H NMR(400MHz,DMSO-d6)δ11.98(s,1H),9.85(s,1H),8.63(d,J＝1.4Hz,1H),8.23(s,1H),8.07(s,1H),7.45(d,J＝8.6Hz,1H),7.35(d,J＝8.6Hz,1H),4.61(s,2H)；13C NMR(100MHz,DMSO-d6)δ163.3,160.7,149.6,135.8,129.4,126.1,125.8,123.7,120.4,114.5,114.2,110.3.C12H10BrN4OS[M+H]+336.9753,found(ESI+)336.9757, the product was determined to be 2- (5-bromo-1H-indol-3-yl) thiazole-4-carbohydrazide.
Step five, dissolving 2- (5-bromo-1H-indol-3-yl) thiazole-4-carbohydrazide (1mmol,1.0equiv.) and benzaldehyde (1.05mmol,1.05equiv.) in ethanol (20mL), heating and reacting at 80 ℃ for 2 hours, cooling to room temperature, and performing suction filtration to obtain a white solid (E) -N' -benzylidene-2- (5-bromo-1H-indol-3-yl) thiazole-4-carbohydrazide (I-1), wherein the yield is 41%, and the melting point is 214-215 ℃;1H NMR(400MHz,DMSO-d6)δ12.07(s,1H),11.82(s,1H),8.66(s,1H),8.54(s,1H),8.30(d,J＝5.9Hz,2H),7.78(s,1H),7.76(s,1H),7.49(d,J＝8.5Hz,4H),7.38(dd,J＝8.6,1.4Hz,1H)；13C NMR(100MHz,DMSO-d6)δ163.4,157.8,149.3,149.2,135.8,134.9,130.6,129.5,129.4,127.7,126.2,125.8,123.3,122.8,114.7,114.3,110.1；C19H14BrN4OS[M+H]+425.0066,found(ESI+)425.0064, the product was identified as (E) -N' -benzylidene-2- (5-bromo-1H-indol-3-yl) thiazole-4-carbohydrazide.
Example 2
Figure BDA0003477269440000081
The preparation method of (E) -2- (5-bromo-1H-indol-3-yl) -N' - (4-methoxybenzylidene) thiazole-4-carbohydrazide shown in the chemical structural formula I-2 comprises the following steps:
same example 1 except that 4-methoxybenzaldehyde was used instead of benzaldehyde in the fifth step, white solid was obtained in 56% yield and melting point>300℃；1H NMR(400MHz,DMSO-d6)δ12.08(s,1H),11.71(s,1H),8.59(s,1H),8.54(s,1H),8.30(s,1H),8.29(s,1H),7.72(d,J＝8.7Hz,2H),7.49(d,J＝8.6Hz,1H),7.39(d,J＝8.6Hz,1H),7.06(d,J＝8.7Hz,2H),3.83(s,3H)；13C NMR(100MHz,DMSO-d6)δ163.4,161.4,157.7,149.3,149.2,135.8,129.5,129.3,127.3,126.1,125.8,123.2,122.6,114.9,114.7,114.3,110.1,55.8；C20H16BrN4O2S[M+H]+455.0172,found(ESI+)455.0173, the product was identified as (E) -2- (5-bromo-1H-indol-3-yl) -N' - (4-methoxybenzylidene) thiazole-4-carbohydrazide.
Example 3
Figure BDA0003477269440000082
The preparation method of (E) -2- (5-bromo-1H-indol-3-yl) -N' - (3,4, 5-trimethoxybenzylidene) thiazole-4-carbohydrazide shown in the chemical structural formula I-3 comprises the following steps:
the same procedure as in example 1 except that 3,4, 5-trimethoxybenzaldehyde is used in the fifth step to replace benzaldehyde, the yield of yellow solid is 42%, and the melting point is 241-242 ℃;1H NMR(400MHz,DMSO-d6)δ12.07(s,1H),11.83(s,1H),8.60(s,1H),8.55(s,1H),8.30(s,2H),7.49(d,J＝8.8Hz,1H),7.38(d,J＝8.8Hz,1H),7.06(s,2H),3.87(s,6H),3.73(s,3H)；13C NMR(100MHz,DMSO-d6)δ163.5,157.8,153.7,149.3,139.8,135.8,130.3,129.5,126.1,125.8,123.3,122.8,114.7,114.3,110.1,104.8,60.6,56.4；C22H20BrN4O4S[M+H]+515.0383,found(ESI+)515.0387, the product was identified as (E) -2- (5-bromo-1H-indol-3-yl) -N' - (3,4, 5-trimethoxybenzylidene) thiazole-4-carbohydrazide.
Example 4
Figure BDA0003477269440000091
The preparation method of (E) -2- (5-bromo-1H-indol-3-yl) -N' - (4-trifluoromethyl benzylidene) thiazole-4-carbohydrazide shown in the chemical structural formula I-4 comprises the following steps:
same example 1 except that 4-trifluoromethylbenzaldehyde was used instead of benzaldehyde in the fifth step, white solid was obtained in a yield of 57% and melting point>300℃；1H NMR(400MHz,DMSO-d6)δ12.08(s,1H),11.86(s,1H),8.66(s,1H),8.54(s,1H),8.31(d,J＝6.1Hz,2H),7.85(s,1H),7.81(s,1H),7.49(d,J＝8.6Hz,1H),7.38(d,J＝8.4Hz,1H),7.32(d,J＝8.5Hz,2H)；13C NMR(100MHz,DMSO-d6)δ164.9,163.5,162.4,157.9，149.2,148.1,135.8,131.4,129.9,129.5,126.1,125.8,123.2,122.9,116.5,116.3,114.7,114.3,110.1,79.6；C20H13BrF3N4OS[M+H]+492.9940,found(ESI+)492.9946, the product was identified as (E) -2- (5-bromo-1H-indol-3-yl) -N' - (4-trifluoromethylbenzylidene) thiazole-4-carbohydrazide.
Example 5
Figure BDA0003477269440000092
The preparation method of (E) -2- (5-bromo-1H-indol-3-yl) -N' - (4-fluorobenzylidene) thiazole-4-carbohydrazide shown in the chemical structural formula I-5 comprises the following steps:
same example 1 except that 4-fluorobenzaldehyde was used in the fifth step instead of benzaldehyde, white solid was obtained in 41% yield and melting point>300℃；1H NMR(400MHz,DMSO-d6)δ12.08(s,1H),12.04(s,1H),8.74(s,1H),8.56(s,1H),8.35(s,1H),8.30(s,1H),7.99(d,J＝8.0Hz,2H),7.85(d,J＝8.2Hz,2H),7.49(d,J＝8.6Hz,1H),7.39(d,J＝8.6Hz,1H)；13C NMR(100MHz,DMSO-d6)δ163.04(s),157.5,148.6,146.9,138.3,135.3,129.1,127.7,125.8,125.7,125.6,125.5,125.3,122.8,114.2,113.8,109.6；C19H13BrFN4OS[M+H]+442.9972,found(ESI+)442.9979, the product was identified as (E) -2- (5-bromo-1H-indol-3-yl) -N' - (4-fluorobenzylidene) thiazole-4-carbohydrazide.
Example 6
Figure BDA0003477269440000101
The preparation method of (E) -2- (5-bromo-1H-indol-3-yl) -N' - (2-bromobenzylidene) thiazole-4-carbohydrazide shown in the chemical structural formula I-6 comprises the following steps:
same example 1 except for the fifth step of substituting 2-bromobenzaldehyde for benzaldehyde, white solid, yield 82%, mp>300℃；1H NMR(400MHz,DMSO-d6)δ12.18(s,1H),12.07(s,1H),9.01(s,1H),8.54(s,1H),8.34(s,1H),8.30(s,1H),8.05(d,J＝7.5Hz,1H),7.72(d,J＝7.9Hz,1H),7.55–7.44(m,2H),7.38(d,J＝8.4Hz,2H)；13C NMR(100MHz,DMSO-d6)δ163.4,158.0,149.1,147.3,135.8,133.7,133.7,132.2,129.5,128.6,127.9,126.2,125.8,124.1,123.3,123.2,114.7,114.3,110.1；C19H13Br2N4OS[M+H]+502.9171,found(ESI+)502.9173, the product was identified as (E) -2- (5-bromo-1H-indol-3-yl) -N' - (2-bromobenzylidene) thiazole-4-carbohydrazide.
Example 7
Figure BDA0003477269440000102
The preparation method of (E) -2- (5-bromo-1H-indol-3-yl) -N' - (4-nitrobenzylidene) thiazole-4-carbohydrazide shown in the chemical structural formula I-7 comprises the following steps:
same example 1 except that 4-nitrobenzaldehyde was used in the fifth step instead of benzaldehyde, white solid was obtained in 97% yield and melting point>300℃；1H NMR(400MHz,DMSO-d6)δ12.15(s,1H),12.09(s,1H),8.77(s,1H),8.55(s,1H),8.37(s,1H),8.34(s,1H),8.31(d,J＝5.9Hz,2H),8.03(d,J＝8.4Hz,2H),7.49(d,J＝8.6Hz,1H),7.39(d,J＝8.4Hz,1H)；13C NMR(100MHz,DMSO-d6)δ163.6,158.0,149.0,148.4,146.6,141.2,135.8,129.6,128.6,126.1,125.8,124.6,123.5,123.3,114.7,114.3,110.1；C19H13BrN5O3S[M+H]+469.9917,found(ESI+)469.9911, the product was identified as (E) -2- (5-bromo-1H-indol-3-yl) -N' - (4-nitrophenylmethylene) thiazole-4-carbohydrazide.
Example 8
Figure BDA0003477269440000111
The preparation method of the 2- (5-bromo-1H-indol-3-yl) -N' - (naphthalene-1-ylmethylene) thiazole-4-carbohydrazide shown in the chemical structural formula I-8 comprises the following steps:
same example 1 except that 1-naphthaldehyde was used in the fifth step instead of benzaldehyde, white solid was obtained in 97% yield and melting point>300℃；E:Z＝8:3；1H NMR(400MHz,DMSO-d6)δ12.11(for E isomer,s,0.8H),11.99(for Z isomer,s,0.3H),11.93(for E isomer,s,0.8H),9.85(for Z isomer,s,0.3H),9.36(for E isomer,s,0.8H),8.88(for E isomer,d,J＝8.5Hz,0.8H),8.63(for Z isomer,s,0.3H),8.56(for E isomer,d,J＝1.6Hz,0.8H),8.36(s,1H),8.33(s,1H),8.23(for Z isomer,s,0.3H),8.09–7.98(m,3H),7.73–7.61(m,2H),7.52–7.34(m,3H),4.61(for Z isomer,s,0.5H)；13C NMR(100MHz,DMSO-d6)δ163.0,157.3,148.7,148.4,135.3,133.5,130.6,130.4,129.6,129.3,128.8,127.4,127.3,126.3,125.6,125.3,124.1,123.1,122.7,122.4,120.0,114.3,114.0,113.8,113.7,109.8,109.6；C23H16BrN4OS[M+H]+475.0223,found(ESI+)475.0225, the product was determined to be 2- (5-bromo-1H-indol-3-yl) -N' - (naphthalen-1-ylmethylene) thiazole-4-carbohydrazide.
Example 9
Figure BDA0003477269440000112
The preparation method of (E) -2- (5-bromo-1H-indol-3-yl) -N' - (pyridine-4-ylmethylene) thiazole-4-carbohydrazide shown in the chemical structural formula I-9 comprises the following steps:
same example 1 except that 4-pyridylaldehyde was used in place of benzaldehyde in the fifth step, white solid was obtained in 54% yield and melting point>300℃；1H NMR(400MHz,DMSO-d6)δ12.13(s,1H),12.09(s,1H),8.69(s,1H),8.67(d,J＝4.2Hz,2H),8.55(s,1H),8.37(s,1H),8.31(s,1H),7.71(d,J＝5.6Hz,2H),7.49(d,J＝8.6Hz,1H),7.39(d,J＝8.6Hz,1H)；13C NMR(100MHz,DMSO-d6)δ163.1,157.5,150.3,148.5,146.2,141.5,135.3,129.1,125.6,125.3,123.0,122.8,121.,114.2,113.8,109.6；C18H13BrN5OS[M+H]+426.0019,found(ESI+)426.0023, the product was identified as (E) -2- (5-bromo-1H-indol-3-yl) -N' - (pyridin-4-ylmethylene) thiazole-4-carbohydrazide.
Example 10
Figure BDA0003477269440000121
The preparation method of (E) -2- (5-bromo-1H-indol-3-yl) -N' - (quinoline-4-ylmethylene) thiazole-4-carbohydrazide shown in the chemical structural formula I-10 comprises the following steps:
same example 1 except that in the fifth step 4-quinolinecarboxaldehyde was used instead of benzaldehyde, white solid was obtained in 80% yield and melting point>300℃；1H NMR(400MHz,DMSO-d6)δ12.18(s,1H),12.12(s,1H),9.38(s,1H),9.03(d,J＝4.4Hz,1H),8.78(d,J＝8.4Hz,1H),8.56(s,1H),8.41(s,1H),8.33(s,1H),8.13(d,J＝8.4Hz,1H),7.91(d,J＝4.5Hz,1H),7.87(t,J＝7.6Hz,1H),7.78(t,J＝7.6Hz,1H),7.50(d,J＝8.6Hz,1H),7.40(d,J＝10.1Hz,1H)；13C NMR(100MHz,DMSO-d6)δ150.8,148.9,146.1,138.0,135.8,130.3,130.1,129.4,128.0,126.1,125.8,125.4,124.7,123.5,123.2,120.0,114.7,114.3,110.1；C26H15BrN5OS[M+H]+476.0175,found(ESI+)476.0177, the product was identified as (E) -2- (5-bromo-1H-indol-3-yl) -N' - (quinolin-4-ylmethylene) thiazole-4-carbohydrazide.
Example 11
Figure BDA0003477269440000122
The preparation method of the 2- (5-bromo-1H-indol-3-yl) -N' - (furan-2-ylmethylene) thiazole-4-carbohydrazide shown in the chemical structural formula I-11 comprises the following steps:
the same procedure as in example 1 was repeated except that in the fifth step, 2-furaldehyde was used instead of benzaldehyde, and the white solid was obtained in 67% yield and a melting point of 251-252 deg.C; e, Z is 3: 1;1H NMR(400MHz,DMSO-d6)δ12.10(for E isomer,s,1H),11.99(for Zisomer,s,0.2H),11.84(for E isomer,s,0.6H),9.85(for Z isomer,s,0.2H),8.63(for Z isomer,s,0.2H),8.56(d,J＝5.9Hz,1H),8.39(for E isomer,d,J＝3.3Hz,0.5H),8.32(d,J＝9.2Hz,1.5H),8.23(for Z isomer,s,0.2H),8.06(for Z isomer,s,0.2H),7.95(for Z isomer,d,J＝1.3Hz,0.2H),7.89(for E isomer,s,0.6H),7.62(for Z isomer,s,0.2H),7.48(d,J＝8.6Hz,1H),7.38(d,J＝8.6Hz,1H),7.17(for Z isomer,d,J＝3.5Hz,0.2H),6.99(for E isomer,d,J＝3.3Hz,0.6H),6.83(for Z isomer,d,J＝3.5Hz,0.2H),6.67(for E isomer,d,J＝1.5Hz,0.6H)；13C NMR(100MHz,DMSO-d6)δ163.0,157.3,149.5,148.6,145.3,138.4,135.3,129.0,125.6,125.3,122.8,122.4,114.2,113.8,113.7,112.3,109.6；C17H12BrN4O2S[M+H]+414.9859,found(ESI+) 414.9863, the product was determined to be 2- (5-bromo-1H-indol-3-yl) -N' - (furan-2-ylmethylene) thiazole-4-carbohydrazide.
Example 12
Figure BDA0003477269440000131
The preparation method of (E) -2- (5-bromo-1H-indol-3-yl) -N' - (cyclohexylmethylene) thiazole-4-carbohydrazide shown in the chemical structural formula I-12 comprises the following steps:
the same procedure as in example 1 was repeated except that the fifth step, in which benzaldehyde was replaced by cyclohexylformaldehyde, gave a white solid in a yield of 62% and a melting point of 286-287 ℃;1H NMR(400MHz,DMSO-d6)δ12.07(s,1H),11.37(s,1H),8.51(s,1H),8.28(s,1H),8.23(s,1H),7.83(s,1H),7.48(d,J＝8.6Hz,1H),7.37(d,J＝8.6Hz,1H),2.30(s,1H),1.87–1.59(m,5H),1.39–1.14(m,5H)；13C NMR(100MHz,DMSO-d6)δ162.8,157.1,156.8,148.9,135.3,128.9,125.6,125.3,122.7,121.8,114.2,113.7,109.6,79.1,29.7,25.5,25.0；C19H20BrN4OS[M+H]+431.0536,found(ESI+)431.0533, the product was identified as (E) -2- (5-bromo-1H-indol-3-yl) -N' - (cyclohexylmethylene) thiazole-4-carbohydrazide.
Example 13
Figure BDA0003477269440000132
The preparation method of (E) -2- (5-bromo-1H-indol-3-yl) -N' - (2-methylpropylidene) thiazole-4-carbohydrazide shown in the chemical structural formula I-13 comprises the following steps:
the same procedure as in example 1 was repeated except that isobutyraldehyde was used in place of benzaldehyde in the fifth step, wherein the yield of white solid was 48%, and mp 258-;1H NMR(400MHz,DMSO-d6)δ12.06(s,1H),11.37(s,1H),8.50(s,1H),8.27(s,1H),8.22(s,1H),7.85(s,1H),7.47(d,J＝8.6Hz,1H),7.37(d,J＝8.6Hz,1H),1.11(d,J＝6.8Hz,7H)；13C NMR(100MHz,DMSO-d6)δ162.8,158.0,157.1,148.8,135.3,128.9,125.6,125.3,122.7,121.9,114.2,113.7,109.6,47.9,31.15,19.61；C16H16BrN4OS[M+H]+391.0223,found(ESI+)391.0225, the product was identified as (E) -2- (5-bromo-1H-indol-3-yl) -N' - (2-methylpropylidene) thiazole-4-carbohydrazide.
Example 14
Figure BDA0003477269440000133
The preparation method of (E) -2- (5-bromo-1H-indol-3-yl) -N' -butylidene thiazole-4-carbohydrazide shown in the chemical structural formula I-14 comprises the following steps:
the white solid yield is 65 percent and mp 272-273 ℃ is carried out in the same way as the example 1 except that the n-butyraldehyde replaces the benzaldehyde in the fifth step;1H NMR(400MHz,DMSO-d6)δ7.39(s,1H),7.15(s,1H),7.04(s,1H),6.78(d,J＝3.9Hz,1H),6.38(d,J＝6.3Hz,1H),6.32(d,J＝6.4Hz,1H),1.45–1.25(m,2H),0.74–0.53(m,3H),0.25(s,4H)；13C NMR(100MHz,DMSO-d6)δ162.8,157.0,153.2,149.0,135.3,129.0,125.6,125.3,122.8,121.8,114.2,113.7,109.6,34.0,19.5,13.7；C16H16BrN4OS[M+H]+391.0223,found(ESI+)391.0227, the product was identified as (E) -2- (5-bromo-1H-indol-3-yl) -N' -butylidenothiazole-4-carbohydrazide.
Example 15
Figure BDA0003477269440000141
The preparation method of (E) -2- (5-bromo-1H-indol-3-yl) -N' -octylidene thiazole-4-carbohydrazide shown in the chemical structural formula I-15 comprises the following steps: the white solid is obtained in the same way as the example 1 except that the n-octanal replaces benzaldehyde in the fifth step, the yield is 66 percent, and the melting point is 223-;1H NMR(400MHz,DMSO-d6)δ7.63(s,1H),7.39(s,1H),7.29(s,1H),7.01(s,1H),6.62(d,J＝8.6Hz,1H),6.57(d,J＝8.6Hz,1H),1.61(m,2H),0.83(m,3H),0.52(m,12H)；13C NMR(100MHz,DMSO-d6)δ163.3,157.5,153.8,149.5,135.8,129.5,126.1,125.8,123.3,122.3,114.7,114.2,110.1,32.6,31.7,29.1,29.0,26.6,22.6,14.4；C20H24BrN4OS[M+H]+447.0849,found(ESI+)447.0855, the product was identified as (E) -2- (5-bromo-1H-indol-3-yl) -N' -octylidene thiazole-4-carbohydrazide.
Example 16
The determination of the anti-tobacco mosaic virus activity of the individual compounds shown as the phytoalexin derivatives I-1 to I-15 is carried out by the following procedures:
the first step, tobacco mosaic virus purification and concentration determination:
the purification and concentration determination of the tobacco mosaic virus are carried out according to the specification of tobacco mosaic virus SOP compiled by the institute of elements, institute of southern development university, the virus crude extract is subjected to 2-time polyethylene glycol centrifugation treatment, the concentration is determined to be 20 mug/mL, and the virus crude extract is refrigerated at 4 ℃ for standby;
secondly, preparing individual compound medicament solutions shown as the plant protector camalexin derivatives I-1 to I-15:
respectively weighing 40mg of individual compounds shown as the derivatives I-1-I-15 of the phytoalexin as raw medicines, and respectively adding 0.4mL of DMF into each raw medicine for dissolving to obtain 1 × 105Mu g/mL mother solution is diluted by Tween 80 aqueous solution with the mass percentage concentration of 1 per mill to the test concentration of 500 mu g/mL or 100 mu g/mL, so as to prepare the individual plant protector calalexin derivatives I-1 to I-15Mixing the above medicinal solution, and diluting ribavirin or ningnanmycin preparation with water to obtain a contrast;
step three, the living body protection function:
respectively selecting ten parts of 3-5 leaf-period Saxisa, respectively spraying the 3-5 leaf-period Saxisa with uniform growth vigor, respectively carrying out the second step of spraying the prepared individual compound medicament solution shown as the plant protecting element camalexin derivative I-1-I-15, repeating the treatment for 3 times, setting a Tween 80 aqueous solution with the mass percentage concentration of 1 thousandth for comparison, spreading 500-mesh carborundum on the leaf surface after 24 hours, dipping the carborundum in a writing brush, lightly wiping the whole leaf surface along the branch vein direction for 2 times, supporting the lower part of the leaf with a palm, washing the leaf with running water after inoculation, repeating the steps for 1 time for 3 times for 3 leaves, recording the number of scabs after 3 days, and calculating the prevention effect;
step four, the in vivo therapeutic effect:
respectively selecting ten 3-5 leaf-stage Saxifraga cigarettes with uniform growth vigor, respectively inoculating viruses to the whole leaves of a writing brush, wherein the virus concentration is 10 microgram/mL, washing the inoculated leaves with running water, spraying the whole plants with the individual compound medicament solution shown by the plant protecting element calalexin derivatives I-1-I-15 prepared in the second step after the leaves are dried, repeating the treatment for 3 times, setting a Tween 80 aqueous solution with the mass percentage concentration of 1 thousandth for comparison, recording the number of disease spots after 3 days, and calculating the control effect;
fifthly, in-vivo passivation:
respectively selecting ten parts of 3-5-leaf-period Saxifragan cigarettes with uniform growth vigor, mixing and passivating the individual compound medicament solution shown by the plant protection element calalexin derivatives I-1-I-15 prepared in the second step with virus juice with the same volume for 30min, performing friction inoculation, wherein the virus concentration is 20 microgrammes/mL, flushing with running water after inoculation, repeating for 3 times, setting the comparison of Tween 80 aqueous solution with the mass percentage concentration of 1 thousandth, and calculating the number of disease spots after 3 days;
the results of measurement of the activity against tobacco mosaic virus of individual compounds represented by the above-mentioned phytoalexin derivatives I-1 to I-15 are shown in Table 1.
TABLE 1 test results of anti-TMV activity of individual compounds represented by the phytoalexin derivatives I-1 to I-15:
Figure BDA0003477269440000151
Figure BDA0003477269440000161
table 1 shows that the plant protection element calalexin derivative has good plant virus resistance activity, under the same test conditions, the dosage is 500 mu g/mL, most of the plant protection element calalexin derivative is superior to commercial varieties of ribavirin, and the compounds I-6 and I-8 show TMV resistance activity equivalent to or higher than that of ningnanmycin at 500 mu g/mL, so that the plant protection element calalexin derivative has development value.
Example 17
The antibacterial activity test and the in vitro sterilization test of individual compounds in the plant protective element calalexin derivatives I-1-I-15 are carried out by the following procedures:
cell growth rate measurement method, i.e. plate method: dissolving 3mg of individual compounds in the plant protector camalexin derivatives I-1-I-15 in 0.03mL of acetone respectively, diluting the solution with 200 mug/mL of Tween 80 aqueous solution until the test concentration is 50mg/kg, sucking 1mL of liquid medicine respectively, injecting the liquid medicine into a culture dish corresponding to the solution, adding 9mL of culture medium respectively, shaking the solution uniformly to prepare a drug-containing flat plate with the concentration of 50 mug/mL, using a flat plate added with 1mL of sterilized purified water as a blank control, cutting a bacterial disc along the outer edge of hypha by using a puncher with the diameter of 4mm, transferring the bacterial disc onto the drug-containing flat plate, repeating the treatment for three times, culturing the culture dish in a constant temperature incubator with the temperature of 24 +/-1 ℃, investigating the expansion diameter of each treated bacterial disc after 48 hours, calculating an average value, and comparing the average value with the blank control to calculate the relative bacteriostasis rate.
Figure BDA0003477269440000162
The results of the in vitro fungicidal activity of the individual compounds in the above-mentioned phytoalexin derivatives I-1 to I-15 are shown in Table 2.
TABLE 2 results of in vitro bactericidal Activity test of Individual Compounds of the phytoalexin derivatives I-1 to I-15
Figure BDA0003477269440000163
Figure BDA0003477269440000171
Table 2 shows that the plant protectant camalexin derivatives have broad-spectrum inhibitory activity on 14 common agricultural pathogens, and under the same test conditions, the inhibition rates of the compounds I-1 and I-13 against phytophthora capsici, rhizoctonia solani and sclerotinia sclerotiorum of rice are obviously superior to that of camalexin, and the compounds I-1 to I-11 show moderate to good bactericidal activity on apple ring rot.
The percentages in the above examples are percentages by mass.
The raw materials and reagents involved in the above examples are commercially available, and the chemical reaction process is within the skill of those in the art.
The invention is not the best known technology.

Claims (6)

1. A calalexin derivative of plant protection agent is characterized in that the structural general formula of the calalexin derivative of plant protection agent is shown as I,
Figure FDA0003477269430000011
wherein R is phenyl, 2-fluorophenyl, 3, 4-difluorophenyl, 2, 6-difluorophenyl, 2, 4-difluorophenyl, 2, 3-difluorophenyl, 4-fluorophenyl, 2-chlorophenyl, 3, 4-dichlorophenyl, 2, 6-dichlorophenyl, 2, 4-dichlorophenyl, 2, 3-dichlorophenyl, 2, 5-dichlorophenyl, 4-chlorophenyl, 5-chloro-2-fluorophenyl, 2-bromophenyl, 3-bromophenyl, 4-iodophenyl, 2-nitrophenyl, 3-nitrophenyl, 4-nitrophenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 2-trifluoromethylphenyl, 3-trifluoromethylphenyl, 4-trifluoromethylphenyl, 3, 5-bis (trifluoromethyl) phenyl, 3-methoxyphenyl, 3,4, 5-tris (methoxy) phenyl, 4-methoxyphenyl, 2-thienyl, 2-furyl, 2-pyridyl, 4-pyridyl, 1-naphthyl, 4-quinolyl, cyclohexyl, cyclopentyl, ethyl, n-propyl, isopropyl, n-butyl, n-pentyl, n-hexyl, n-heptyl, n-octyl or benzyl.
2. A phytoalexin derivative according to claim 1, characterized in that the preferred compound is:
Figure FDA0003477269430000012
wherein, the compound shown in the chemical structural formula I-1 is (E) -N ' -benzylidene-2- (5-bromo-1H-indol-3-yl) thiazole-4-carbohydrazide, the compound shown in the chemical structural formula I-2 is (E) -2- (5-bromo-1H-indol-3-yl) -N ' - (4-methoxybenzylidene) thiazole-4-carbohydrazide, the compound shown in the chemical structural formula I-3 is (E) -2- (5-bromo-1H-indol-3-yl) -N ' - (3,4, 5-trimethoxybenzylidene) thiazole-4-carbohydrazide, the compound shown in the chemical structural formula I-4 is (E) -2- (5-bromo-1H-indol-3-yl) -N '- (4-trifluoromethyl benzylidene) thiazole-4-carbohydrazide, the compound shown in the chemical structural formula I-5 is (E) -2- (5-bromo-1H-indol-3-yl) -N' - (4-fluorobenzylidene) thiazole-4-carbohydrazide, the compound shown in the chemical structural formula I-6 is (E) -2- (5-bromo-1H-indol-3-yl) -N '- (2-bromobenzylidene) thiazole-4-carbohydrazide, and the compound shown in the chemical structural formula I-7 is (E) -2- (5-bromo-1H-indol-3-yl) -N' - (2-bromobenzylidene) thiazole-4-carbohydrazide -1H-indol-3-yl) -N '- (4-nitrobenzylidene) thiazole-4-carbohydrazide which is represented by the chemical structural formula I-8 and is 2- (5-bromo-1H-indol-3-yl) -N' - (naphthalen-1-ylmethylene) thiazole-4-carbohydrazide, which is represented by the chemical structural formula I-9 and is (E) -2- (5-bromo-1H-indol-3-yl) -N '- (pyridin-4-ylmethylene) thiazole-4-carbohydrazide, which is represented by the chemical structural formula I-10 and is (E) -2- (5-bromo-1H-indol-3-yl) -N' - (quinoline-4- Methylene) thiazole-4-carbohydrazide, wherein the compound shown in the chemical structural formula I-11 is 2- (5-bromo-1H-indol-3-yl) -N ' - (furan-2-ylmethylene) thiazole-4-carbohydrazide, the compound shown in the chemical structural formula I-12 is E) -2- (5-bromo-1H-indol-3-yl) -N ' - (cyclohexylmethylene) thiazole-4-carbohydrazide, the compound shown in the chemical structural formula I-13 is (E) -2- (5-bromo-1H-indol-3-yl) -N ' - (2-methylpropylidene) thiazole-4-carbohydrazide, the compound shown in the chemical structural formula I-14 is (E) -2- (5-bromo-1H-indol-3-yl) -N '-butylidene thiazole-4-carbohydrazide, and the compound shown in the chemical structural formula Ia-15 is (E) -2- (5-bromo-1H-indol-3-yl) -N' -octylidene thiazole-4-carbohydrazide.
3. The process for preparing a calalexin derivative as claimed in claim 1, wherein said process comprises the steps of:
(1) taking 5-bromo-1H-indole-3-thiocarboxamide (3e) as a raw material, and heating and refluxing the raw material and 3-bromoethyl pyruvate in an ethanol solvent to react to obtain a compound 5;
wherein, the mol ratio is that 5-bromine-1H-indole-3-thiocarboxamide: ethyl 3-bromopyruvate ═ 1: 1-1.5, adding 5-20 mL of ethanol into 5-bromo-1H-indole-3-thiocarboxamide per millimole, wherein the reaction time is 1-4H and the temperature is 75-85 ℃;
(2) taking a compound 5 and 80% hydrazine hydrate as raw materials, and heating and refluxing the raw materials in an ethanol solvent to react to obtain a compound 6;
wherein, the molar ratio is that the compound 5: hydrazine hydrate 1: 3-10, adding 15-30 mL of ethanol into each millimole of compound 5, wherein the reaction time is 1-4 h, and the temperature range is 75-85 ℃;
(3) a method for preparing compounds I-1 to I-15 comprises the following steps:
taking a compound 6 and an aldehyde compound as raw materials, and heating and refluxing the raw materials in an ethanol solvent to obtain compounds I-1 to I-15;
wherein, the molar ratio is that compound 6: aldehyde compound is 1: 1-2, adding 15-30 mL of ethanol into each millimole of compound 6, wherein the reaction time is 1-4 h, and the temperature range is 75-85 ℃;
the aldehyde compound is benzaldehyde, 2-fluorobenzaldehyde, 3, 4-difluorobenzaldehyde, 2, 6-difluorobenzaldehyde, 2, 4-difluorobenzaldehyde, 2, 3-difluorobenzaldehyde, 4-fluorobenzaldehyde, 2-chlorobenzaldehyde, 3, 4-dichlorobenzaldehyde, 2, 6-dichlorobenzaldehyde, 2, 4-dichlorobenzaldehyde, 2, 3-dichlorobenzaldehyde, 2, 5-dichlorobenzaldehyde, 4-chlorobenzaldehyde, 5-chloro-2-fluorobenzaldehyde, 2-bromobenzaldehyde, 3-bromobenzaldehyde, 4-iodobenzaldehyde, 2-nitrobenzaldehyde, 3-nitrobenzaldehyde, 4-nitrobenzaldehyde, 3-nitrobenzaldehyde, or mixture of benzaldehyde, 2-methylbenzaldehyde, 3-methylbenzaldehyde, 4-methylbenzaldehyde, 2-trifluoromethylbenzaldehyde, 3-trifluoromethylbenzaldehyde, 4-trifluoromethylbenzaldehyde, 3, 5-bis (trifluoromethyl) benzaldehyde, 3-methoxybenzaldehyde, 3,4, 5-tris (methoxy) benzaldehyde, 4-methoxybenzaldehyde, 2-thiophenecarboxaldehyde, 2-furancarbaldehyde, 2-pyridinecarboxaldehyde, 4-pyridinecarboxaldehyde, 1-naphthaldehyde, 4-quinolinecarboxaldehyde, cyclohexylcyclohexanecarboxaldehyde, cyclopentylcyclohexanecarboxaldehyde, n-propionaldehyde, n-butyl, isobutyl, n-valeraldehyde, n-hexanal, n-heptanal, n-octanal, n-nonanal or phenylacetaldehyde.
4. Use of a camalexin derivative according to claim 1, characterized by being used as an anti-plant virus agent, or anti-plant pathogenic agent.
5. Use of a camalexin derivative according to claim 4, characterized in that the plant virus is tobacco mosaic virus, pepper virus, rice virus, tomato virus, sweet potato virus, melon virus or maize dwarf mosaic virus.
6. The use of a camalexin derivative as claimed in claim 1, wherein the phytopathogen is tomato early blight, gibberella zeae, pyricularia grisea, phytophthora capsici, sclerotia napellus, rhizoctonia solani, botrytis cinerea, cucumber fusarium wilt, peanut brown spot, apple ring rot, wheat grain wither, corn small spot, watermelon anthrax or rice bakanae.
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Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104496980A (en) * 2014-12-19 2015-04-08 南阳师范学院 Novel thiazole heterocyclic compound as well as preparation method and application thereof
CN107652296A (en) * 2016-07-26 2018-02-02 南开大学 Loop coil Oxoindole acyl hydrazone derivative and preparation method thereof and the application in terms of preventing and treating plant virus, sterilization, desinsection
CN109422745A (en) * 2017-08-21 2019-03-05 南开大学 Matrine acyl hydrazone derivative and its preparation and the application in terms of preventing and treating plant pest
CN110759893A (en) * 2018-07-26 2020-02-07 南开大学 Hyrtinadidine alkaloid derivative, preparation thereof and application thereof in resisting plant viruses and germs
CN110759896A (en) * 2018-07-26 2020-02-07 南开大学 Piperazine dione acylhydrazone derivative, preparation method thereof and application of piperazine dione acylhydrazone derivative in plant virus prevention and control, sterilization and disinsection

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104496980A (en) * 2014-12-19 2015-04-08 南阳师范学院 Novel thiazole heterocyclic compound as well as preparation method and application thereof
CN107652296A (en) * 2016-07-26 2018-02-02 南开大学 Loop coil Oxoindole acyl hydrazone derivative and preparation method thereof and the application in terms of preventing and treating plant virus, sterilization, desinsection
CN109422745A (en) * 2017-08-21 2019-03-05 南开大学 Matrine acyl hydrazone derivative and its preparation and the application in terms of preventing and treating plant pest
CN110759893A (en) * 2018-07-26 2020-02-07 南开大学 Hyrtinadidine alkaloid derivative, preparation thereof and application thereof in resisting plant viruses and germs
CN110759896A (en) * 2018-07-26 2020-02-07 南开大学 Piperazine dione acylhydrazone derivative, preparation method thereof and application of piperazine dione acylhydrazone derivative in plant virus prevention and control, sterilization and disinsection

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
PEDRAS, M. SOLEDADE C.; ABDOLI, ABBAS: "Methoxycamalexins and related compounds: Syntheses, antifungal activity and inhibition of brassinin oxidase", 《BIOORGANIC & MEDICINAL CHEMISTRY》, vol. 26, no. 15, pages 12 - 13 *
刘娟娟等: "异海松基水杨酰腙的合成及细胞毒性评价", 《林产化学与工业》, vol. 37, no. 4, pages 35 - 36 *
王珍珍等: "阿魏酸酰腙类化合物的合成及生物活性", 《化学通报》, vol. 84, no. 9, pages 947 - 948 *

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