CN104693035B - Salicylic acid trans-(beta)-farnesene analogues and application thereof - Google Patents

Salicylic acid trans-(beta)-farnesene analogues and application thereof Download PDF

Info

Publication number
CN104693035B
CN104693035B CN201510076763.9A CN201510076763A CN104693035B CN 104693035 B CN104693035 B CN 104693035B CN 201510076763 A CN201510076763 A CN 201510076763A CN 104693035 B CN104693035 B CN 104693035B
Authority
CN
China
Prior art keywords
salicylic acid
trans
farnesene
methyl
preparation
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired - Fee Related
Application number
CN201510076763.9A
Other languages
Chinese (zh)
Other versions
CN104693035A (en
Inventor
杨新玲
秦耀果
宋敦伦
张景朋
凌云
谭晓庆
曲焱焱
李文浩
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
China Agricultural University
Original Assignee
China Agricultural University
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by China Agricultural University filed Critical China Agricultural University
Priority to CN201510076763.9A priority Critical patent/CN104693035B/en
Publication of CN104693035A publication Critical patent/CN104693035A/en
Priority to PCT/CN2016/000006 priority patent/WO2016127723A1/en
Application granted granted Critical
Publication of CN104693035B publication Critical patent/CN104693035B/en
Expired - Fee Related legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C67/00—Preparation of carboxylic acid esters
    • C07C67/03—Preparation of carboxylic acid esters by reacting an ester group with a hydroxy group
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C201/00—Preparation of esters of nitric or nitrous acid or of compounds containing nitro or nitroso groups bound to a carbon skeleton
    • C07C201/06—Preparation of nitro compounds
    • C07C201/12—Preparation of nitro compounds by reactions not involving the formation of nitro groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C205/00—Compounds containing nitro groups bound to a carbon skeleton
    • C07C205/49—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by carboxyl groups
    • C07C205/57—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by carboxyl groups having nitro groups and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton
    • C07C205/59—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by carboxyl groups having nitro groups and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton the carbon skeleton being further substituted by singly-bound oxygen atoms
    • C07C205/60—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by carboxyl groups having nitro groups and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton the carbon skeleton being further substituted by singly-bound oxygen atoms in ortho-position to the carboxyl group, e.g. nitro-salicylic acids
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C231/00—Preparation of carboxylic acid amides
    • C07C231/02—Preparation of carboxylic acid amides from carboxylic acids or from esters, anhydrides, or halides thereof by reaction with ammonia or amines
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C235/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
    • C07C235/42—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton
    • C07C235/44—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton with carbon atoms of carboxamide groups and singly-bound oxygen atoms bound to carbon atoms of the same non-condensed six-membered aromatic ring
    • C07C235/58—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton with carbon atoms of carboxamide groups and singly-bound oxygen atoms bound to carbon atoms of the same non-condensed six-membered aromatic ring with carbon atoms of carboxamide groups and singly-bound oxygen atoms, bound in ortho-position to carbon atoms of the same non-condensed six-membered aromatic ring
    • C07C235/60—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton with carbon atoms of carboxamide groups and singly-bound oxygen atoms bound to carbon atoms of the same non-condensed six-membered aromatic ring with carbon atoms of carboxamide groups and singly-bound oxygen atoms, bound in ortho-position to carbon atoms of the same non-condensed six-membered aromatic ring having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C67/00—Preparation of carboxylic acid esters
    • C07C67/08—Preparation of carboxylic acid esters by reacting carboxylic acids or symmetrical anhydrides with the hydroxy or O-metal group of organic compounds
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
    • C07C69/76—Esters of carboxylic acids having a carboxyl group bound to a carbon atom of a six-membered aromatic ring
    • C07C69/84—Esters of carboxylic acids having a carboxyl group bound to a carbon atom of a six-membered aromatic ring of monocyclic hydroxy carboxylic acids, the hydroxy groups and the carboxyl groups of which are bound to carbon atoms of a six-membered aromatic ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
    • C07C69/76—Esters of carboxylic acids having a carboxyl group bound to a carbon atom of a six-membered aromatic ring
    • C07C69/84—Esters of carboxylic acids having a carboxyl group bound to a carbon atom of a six-membered aromatic ring of monocyclic hydroxy carboxylic acids, the hydroxy groups and the carboxyl groups of which are bound to carbon atoms of a six-membered aromatic ring
    • C07C69/92—Esters of carboxylic acids having a carboxyl group bound to a carbon atom of a six-membered aromatic ring of monocyclic hydroxy carboxylic acids, the hydroxy groups and the carboxyl groups of which are bound to carbon atoms of a six-membered aromatic ring with etherified hydroxyl groups

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Agricultural Chemicals And Associated Chemicals (AREA)

Abstract

The invention discloses salicylic acid trans-(beta)-farnesene analogues as well as a preparation method and an application thereof, and belongs to the field of organic compound synthesis. The compound as shown in a formula I in the specification is obtained by the following steps of: mixing salicylic acid and analogues of salicylic acid, geraniol, geranylamine or substituted geranylamine serving as raw materials with an organic solvent, carrying out condensation reaction to obtain the salicylic acid trans-(beta)-farnesene analogues with different substitutes, and carrying out silica-gel column chromatography separation and purification. The preparation method of the compound as shown in the formula I has the advantages of mild reaction, simple and easy operation, relatively high yield and relatively low cost; and the compound is more stable than trans-(beta)-farnesene. The compound as shown in the formula I has multiple biological activities, relatively good killing activity to aphids at high dose, warning repellant activity to aphids at low dose, tobacco mosaic virus resisting activity and bactericidal activity, can be used for pest control and disease prevention in the agricultural production, and has relatively high application and development value.

Description

Trans- (the β)-farnesene analog of salicylic acid and its application
Technical field
The invention belongs to organic chemical synthesis field, and in particular to trans- (the β)-farnesene analog of salicylic acid and its system Preparation Method, and application of such compound in control of aphids, plant disease-resistant and sterilization.
Background technology
When Aphid Alarm Pheromone is that aphid is attacked by natural enemy, the oozy oily drop of cornical, it can make surrounding Aphid produces alarm function, stops taking food, and harm scene is fled from rapidly, so as to stop that host plant is caused harm.Bowers and Edwards etc. 1972 separate first identify Aphid Alarm Pheromone main component be (anti-)-β-farnesene ((E)-β- Farnesene, abbreviation EBF.The research such as Francis finds that EBF is the main component of Aphid Alarm Pheromone, or even is with EBF Sole component has 12 kinds of aphids.Result of study shows that Aphid Alarm Pheromone also has in addition to well-known activity of reporting to the police Other multi-biological activity, such as EBF can regulate and control the ratio of alatae and wingless aphid in aphid offspring；EBF is to some insects With the function similar to juvenile hormone III, the development by metamorphosis of insect is affected；EBF has in 100ng/ aphid dosage to aphid Obvious toxic action, and when EBF is mixed with commercialization medicament imidacloprid prevent eliminating aphis when, synergistic effect can be played.Enter One step research finds that EBF there is kairomone to act on natural enemy of aphid；EBF can also induce wasp fly, aphid parasite to position and prey on Aphid, and adjust the oviposition behavior of wasp fly.Francis etc. it is quantitative to have studied inductions of the EBF to natural enemy of aphid ladybug anti- Should, there is obvious inducing action to ladybug when EBF consumptions are more than 2g；EBF synthetic genes are incorporated in potato crop can To discharge EBF, the effect of its repellent aphid is less desirable, but it can effectively attract natural enemy of aphid Chrysopa.
The structural formula of EBF is as shown in formula A：From the structural formula of EBF it is seen that, containing multiple double bonds, especially end There are a pair of conjugated double bonds, therefore EBF is easily oxidized in atmosphere and volatile, property is unstable, limits EBF in field Between application.For such case, lot of domestic and foreign researcher carries out structure of modification modification to EBF molecules, expects to find The compound that Activity and stabill has both.
Structure of modification and modification with regard to EBF, domestic and international expert is respectively from reduction degree of unsaturation, introducing hetero-atoms, raising The aspects such as molecular weight, left end double bond opening are started with, and have been obtained some and have been had certain biologically active and the preferable EBF classes of stability concurrently Like thing (Nishino et al.Applied Entomology and Zoology.1976,11 (4), 340-343；Bowers et al.Journal of Insect Physiology.1977,23(6),697-701；Dawson et al.Journal of Chemical Ecology.1982,8(11),1377-1388；Gibson et al.Annals of Applied Biology.1984,104(2),203-209；Briggs et al.Pestic.Sci.1986,17(4),441-448；Li Zhengming Deng, chemical journal, 1987,45 (11):1124-1128；Zhang Zhongning etc., insect journal, 1988,31 (4):435-438).In recent years Come, nitrogen heterocyclic ring, such as imidazolidine, oxadiazine ring, pyrazole ring and other nitrogen heterocyclic rings are introduced in (anti-)-β-farnesene structure Deng synthesizing the part of compounds that obtains has preferable inhibitory activity to aphid, is the exploitation of potential new aphid controlling agent With application there is provided good theoretical and apply foundation.(Yang Xin's tinkling of pieces of jade etc., SCI, 2004,25 (9):1657- 1661；Organic chemistry, 2008,28 (4):617-621；Chinese invention patent：CN200310113701.8, CN200410098491.4, CN200710121334, CN201010564801.2, CN201110084058.5).
Salicylic acid level is closely related with the generation of disease resistance of plant in plant body, and salicylic acid is important can to activate plant Thing allergic reaction and the Inner source signal molecules of systemic acquired resistance, salicylic acid can induce plant correlation disease-resistant gene and albumen Produce, make plant obtain systemic disease resistance, if the plant such as evoking tobacco and cucumber is to multiple diseases such as bacterium, fungi, viruses Disease resistance (Malamy, J.et al.Science.1990,250 (4983)：1002-1004；Former soldier etc. forever, BULLETIN OF BOTANY Vol., 1994,11(3)：1-9；A.Corina Vlot et al.Annual Review of Phytopathology.2009,47: 177–206；Milwaukee et al.Nature.2012,486:198-199).Salicylic acid and its analogs are in field of medicaments and anti-corrosion Antibacterial direction also have more in-depth study (Alib et al.J.Pharmacol Exp Ther, 1983,226 (2):589- 594)。
The method that the present invention is spliced using active substructure, by the water with plant disease-resistant induced activity and antibacterial activity Poplar acids active group is incorporated in (anti-)-β-farnesene, substitutes the conjugated double bond in (anti-)-β-farnesene structure to improve it Stability and its action spectrum is widened, invented a class containing salicylic acid (anti-)-β-farnesene analog.
The content of the invention
An object of the present invention is to provide a class salicylic acid trans-beta-farnesene analog.
The second object of the present invention is to provide the preparation method of a class salicylic acid trans-beta-farnesene analog.
The third object of the present invention is to provide a class salicylic acid trans-beta-farnesene analog as new aphid controlling agent Application.
The fourth object of the present invention be to provide a class salicylic acid trans-beta-farnesene analog as plant antiviral agent and The application of bactericide.
The fifth object of the present invention is to provide a class salicylic acid trans-beta-farnesene analog as having pest control treatment medicine concurrently The application of thing.
One class salicylic acid trans-beta-farnesene analog, it is characterised in that the general structure (formula I) of the compound is：
Wherein R1For H, C1～C10 alkyl, haloalkyl, phenyl, (halogen-containing, nitro, C1～10 alkyl and alkoxyl take The phenyl in generation), benzyl (benzyl that halogen-containing, nitro, C1～10 alkyl and alkoxyl replace), halogen, nitro, C1～10 alkyl And phenyl, thiazole, the pyridine that alkoxyl replaces；R2For H, OH, C1～C10 alkyl, C1～C10 alkoxyls, haloalkyl, halogen Element, nitro, trifluoromethyl；R3For the phenyl that H, C1～C10 alkyl, halogen, nitro, C1～10 alkyl and alkoxyl replace；X is O、N；Y is O, S.
Preferably, R1For H, methyl, ethyl, phenyl, benzyl；R2For H, OH, methyl, methoxyl group, Cl, F, CF3、NO2；R3For H、CH3；X is O, N；Y is O.
The preparation method of trans- (the β)-farnesene analog of salicylic acid is comprised the following steps：
In the presence of dehydrating agent and condensing agent or acid binding agent, in organic solvent by geraniol, spiceleaf amine or replacement spiceleaf Amine in the presence of catalyst, carries out condensation reaction with the compound shown in formula II, obtains the compound shown in Formulas I：
Wherein R1For H, C1-C10 alkyl, haloalkyl, phenyl, (halogen-containing, nitro, C1-10 alkyl and alkoxyl replace Phenyl), benzyl (benzyl that halogen-containing, nitro, C1-10 alkyl and alkoxyl replace), halogen, nitro, C1-10 alkyl and alkane Thiazole, pyridine that epoxide replaces；R2For H, OH, C1-C10 alkyl, C1-C10 alkoxyls, haloalkyl, halogen, nitro, trifluoro Methyl；R3For the phenyl that H, C1-C10 alkyl, halogen, nitro, C1-10 alkyl and alkoxyl replace；Y is O, S.
Compound provided by the present invention follows the steps below preparation：
Work as R1It is H, C1-C10 alkyl, haloalkyl, (halogen-containing, nitro, C1-10 alkyl and alkoxyl replace phenyl Phenyl) when, type I compound synthesis is comprised the following steps：Salicylic acid is mixed with organic solvent, dehydration is then gradually added into successively Agent and condensing agent or acid binding agent, mix with geraniol or spiceleaf amine or replacement spiceleaf amine, catalyst and organic solvent, are condensed Solvent is sloughed in reaction, decompression, and silica gel column chromatography is separated, and obtains the compound shown in formula I.
Work as R1It is benzyl (benzyl that halogen-containing, nitro, C1-10 alkyl and alkoxyl replace), halogen, nitro, C1-10 alkane When thiazole, pyridine that base and alkoxyl replace, type I compound synthesis is comprised the following steps：Salicylic acid is mixed with organic solvent, Benzyl bromine or halogenated aryl hydrocarbon are added, under phase transfer catalyst effect key intermediate substituted salicylic acid is obtained, then sequentially added Dehydrating agent and condensing agent or acid binding agent, then mix with geraniol or spiceleaf amine or replacement spiceleaf amine, catalyst and organic solvent, enter Solvent is sloughed in row condensation reaction, decompression, and silica gel column chromatography is separated, and obtains the compound shown in formula I.
Reaction equation is as follows：
In the preparation process of trans- (the β)-farnesene analog of salicylic acid, the range of reaction temperature is wider, is -50 DEG C ～200 DEG C, preferable reaction temperature is 20 DEG C～50 DEG C.
Organic solvent used includes methyl alcohol, ethanol, normal propyl alcohol, isopropanol, benzene,toluene,xylene, acetonitrile, propionitrile, fourth Nitrile, acetone, butanone, methylisobutylketone, N,N-dimethylformamide, DMAC N,N' dimethyl acetamide, N- methyl-formailide, N- Methyl pyrrolidone, HMPA, dimethyl sulfoxide, petroleum ether, methyl acetate, ethyl acetate, ether, diisopropyl ether, Glycol monoethyl ether, ethylene glycol monoethyl ether, diethylene glycol monomethyl ether, diethylene glycol monoethyl ether, glycol dimethyl ether, dichloromethane At least one or more than one any combination in alkane, chloroform, carbon tetrachloride, hexane, hexamethylene, tetrahydrofuran.
Described dehydrating agent is selected from dicyclohexylcarbodiimide, N, N- DICs, 1- (3- dimethylaminos third Base) -3- ethyl carbodiimides one or more any combination；Condensing agent is N, N ＇-carbonyl dimidazoles；Catalyst is 4- Dimethylamino naphthyridine, acid binding agent is organic base or inorganic base, preferably piperidines, NaOH, potassium carbonate, pyridine, triethylamine, carbon Sour sodium, potassium carbonate, sodium acid carbonate, saleratus, sodium methoxide and sodium hydride one or more any combination.
Described phase transfer catalyst is polyethers：Chain polyethylene glycol, chain dialkylethers, cyclic crown ether Class：18 hats 6,15 are preced with, cyclodextrin, quaternary ammonium salt：Benzyltriethylammoinium chloride (TEBA), TBAB, tetrabutylammonium chloride, 4-butyl ammonium hydrogen sulfate (TBAB), tri-n-octyl methyl ammonium chloride, DTAC, tetradecyltrimethylammonium chlorination Ammonium etc., tertiary amines:One or more any combination in R4N X, pyridine, tri-n-butylamine etc., quaternary ammonium base, season phosphonium salt etc..
In methods described, product is obtained by column chromatography purifying.
Trans- (the β)-farnesene analog of salicylic acid is also the scope of the present invention for the medicine of active component.
Trans- (the β)-farnesene analog of salicylic acid of the present invention, has been experimentally verified that obvious chemistry kills aphid effect and drives Activity is kept away, i.e., there are direct chemopreventive effects to aphid, also with the activity of regulation and control aphid behavior, can be used as aphid control Agent, for preventing and treating crops, fruit tree, Chinese herbal medicine and Flower Pests, is preferred for anti-eliminating aphis；
Trans- (the β)-farnesene analog of salicylic acid of the present invention, is experimentally verified that to tobacco mosaic virus (TMV) and various cause of diseases Bacterium has an inhibitory activity, and wherein pathogen is gibberellic hypha, sheath blight fungus, early epidemic germ, brown spot pathogen or anthrax bacteria, therefore Can agriculturally apply as plant disease-resistant bactericide.
Beneficial effects of the present invention：Trans- (the β)-farnesene analog of salicylic acid of present invention synthesis, preparation method is simple Easy, simple to operate, easily, cost is relatively low for product purification, and (β)-farnesene molecular weight trans- compared with guide is big, and stability is improved； The compound invented has multi-biological activity, and not only there is obvious killing effect and repellent to live to agricultural pests aphid Property, but also with plant disease-resistant cytotoxic activity and bactericidal activity, therefore can apply simultaneously anti-in insect and corps diseases Control aspect.
Specific embodiment
The present invention is described further with following several lower embodiments, but the present invention is not limited in these embodiments, under The method in embodiment is stated, if no special instructions, conventional method is.
Embodiment 1：The preparation of 3- methoxysalicylic acids-(E) -3,7- dimethyl -2,6- octadiene esters (I-10)
In 100ml there-necked flasks, 2.18g 3- methoxysalicylic acids, 3.20g DCC and 1.74g DMAP and 20mL are added THF, is added dropwise 2.00g geraniols, and 20 DEG C are reacted 3 hours.Extracted three times with water, take organic phase, solvent, silica gel column layer are sloughed in decompression (eluent is petroleum ether for analysis separation：Ethyl acetate V：V=500: 1), obtains yellow liquid 3- methoxysalicylic acids-(E) -3,7- bis- Methyl -2,6- octadiene esters (I-10), yield 53.8%.1H NMR：11.10(s,1H,ArOH),7.26-7.47(m,1H, ), ArH 7.02-7.09 (m, 1H, ArH), 6.81 (t, 1H, J=8.07Hz, ArH), 5.43-5.48 (m, 1H ,=CH), 5.08- 5.10 (m, 1H ,=CH), 4.87 (d, 2H, J=7.14Hz, CH2),3.90(s,3H,ArOCH3),2.10-2.14(m,4H, CH2CH2),1.80(s,3H,CH3),1.75(s,3H,CH3),1.60(s,3H,CH3)。
The targeted of I-2～I-4, I-12～I-14, I-18～I-25 and I-27～I-38 is respectively with legal system call number Compound.
Embodiment 2：The preparation of 3- hydroxyl salicylic acids-(E) -3,7- dimethyl -2,6- octadiene esters (I-5)
Step 1：The preparation of 3- hydroxyls salicylic acid acetonitrile ester (intermediate 1)
In 100ml there-necked flasks, 0.50g 3- hydroxyl salicylic acids, 0.29g chloroacetonitriles, 0.49g triethylamines and 20mL are added Acetone, back flow reaction 6 hours.CH is used respectively2Cl2Extract three times with water, take organic phase, solvent, silica gel column chromatography point are sloughed in decompression From obtaining yellow oily liquid 3- hydroxyl salicylic acid acetonitrile ester, yield 75%.
Step 2：The preparation of 3- hydroxyl salicylic acids-(E) -3,7- dimethyl -2,6- octadiene esters (I-5)
In 100ml there-necked flasks, 2.00g 3- hydroxyl salicylic acid acetonitrile esters, 2.19g potassium carbonate, 1.80g geraniols are added With 40mL DMFs, 90 DEG C are reacted 6 hours.Water is extracted, and solvent is sloughed in decompression, and silica gel column chromatography separates (wash-out Liquid is petroleum ether：Ethyl acetate V：V=500: 1), obtains yellow liquid 3- hydroxyl salicylic acids-(E) -3,7- dimethyl -2,6- pungent two Alkene ester (I-5), yield 24.1%.1H NMR：7.37-7.40(m,1H,ArH),7.08-7.71(m,1H,ArH),6.78(t, 1H, J=8.01Hz, ArH), 5.88-5.90 (m, 1H ,=CH), 5.43-5.48 (m, 1H ,=CH), 5.08 (d, 2H, J= 6.21Hz,CH2),2.06-2.22(m,4H,CH2CH2),1.77(s,3H,CH3),1.67(s,3H,CH3),1.60(s,3H, CH3)。
The target compound of I-1, I-6 and I-26 is respectively with legal system call number.
Embodiment 3：The preparation of 3- methyl -2- benzyloxies-salicylic acid-(E) -3,7- dimethyl -2,6- octadiene esters (I-7)
Step 1：The preparation of 3- methyl -2- benzyloxy benzyl salicylates (intermediate 2)
In 100ml there-necked flasks, add 2.00g 3- cresotinic acids, 6.75g cylites, the NaOH of 1.59g tri-, 0.68gTBAB and 15mL CH2Cl2, 15mL water, room temperature reaction 4 hours.Washing three times, takes organic phase, and solvent, silicon are sloughed in decompression Plastic column chromatography is separated, and obtains light yellow liquid 3- methyl -2- benzyloxy benzyl salicylates, yield 97%.
Step 2：The preparation of 3- methyl -2- benzyloxy salicylic acids (intermediate 3)
In 100ml there-necked flasks, 3.18g 3- methyl -2- benzyloxy benzyl salicylates, 1.10g NaOH and 35mL are added Ethanol, back flow reaction 4 hours.Solvent is sloughed in decompression, and watery hydrochloric acid acidifying obtains white solid 3- methyl -2- benzyloxy salicylic acids, receives Rate 98%.
Step 3：The preparation of 3- methyl -2- benzyloxies-salicylic acid-(E) -3,7- dimethyl -2,6- octadiene esters (I-7)
In 100ml there-necked flasks, 1.60g 3- methyl -2- benzyloxy salicylic acids, 1.53g DCC and 0.83g DMAP are added With 20mL THF, 0.95g geraniols are added dropwise, 20 DEG C are reacted 3 hours.Extracted three times with water, take organic phase, solvent is sloughed in decompression, (eluent is petroleum ether for silica gel column chromatography separation：Ethyl acetate V：V=50: 1), obtain weak yellow liquid 3- methoxysalicylic acids- (E) -3,7- dimethyl -2,6- octadiene esters (I-7), yield 41.7%.1H NMR：7.66-7.69(m,1H,ArH),7.47- 7.50 (m, 2H, ArH), 7.33-7.41 (m, 4H, ArH), 7.07 (t, 1H, J=15.31Hz, ArH), 5.39-5.44 (m, 1H, =CH), 5.07-5.09 (m, 1H ,=CH), 4.96 (s, 2H, CH2), 4.81 (d, 2H, J=7.12Hz, CH2), 2.31 (s, 3H, ArCH3),2.02-2.09(m,4H,CH2CH2),1.70(s,3H,CH3),1.64(s,3H,CH3),1.59(s,3H,CH3)
The target compound of I-8～I-9, I-11, I-15～I-17 and I-39～I-42 is respectively with legal system call number.
Table 1 below lists the structure of target compound and basic physicochemical data, and they are according to similar to aforementioned reality Apply prepared by the various methods shown in example.
The physicochemical data of the target compound of table 1 (Formulas I)
Embodiment 4：To the insecticidal activity of aphid under the compounds of this invention high concentration
Target compound a ten thousandth balance is weighed into 50mg compound samples in 20ml measuring cups, 10mL capacity is imported Bottle is made into the measure liquid of 5000mg/L.Take 1ml acetone with 1-5ml liquid-transfering guns again and add measuring cup, add 9ml to contain 0.1% bent The aqueous solution of logical X-100 is drawn, is fully mixed, obtain the measure liquid of 500mg/L.By indoor culture not in contact with excessively any medicament and insect Soybean leaves, get the blade of suitable size with the card punch of diameter 15mm, respectively 15 seconds in the liquid that diluted of immersion, take Go out to dry, in being put into raw drafting board, blade back faces up, bottom adds 1% agar moisturizing, soybean aphid 20 is accessed per hole, each It is repeated 3 times.Inspection result after 48 hours.Dead criterion is：Touch polypide, it is impossible to which individuality of normally creeping is considered as death.
Corrected mortality is calculated, formula is as follows:
Corrected mortality (%)=(the sample death rate-blank death rate)/(the 1- blank death rates) * 100
Kill aphid active testing and the results are shown in Table 2
Insecticidal activity (concentration 500mg/L) of the Formulas I partial target compound of table 2 to bean aphid
The result of table 2 shows that the compound of the present invention has in higher concentrations kill activity, wherein compound I- to aphid 10th, I-14, I-15, I-16, I-17, I-18, I-19 and I-25 exist under the dosage of 500mg/L to the suppression death rate of aphid More than 80%, with the value further developed as control of aphids agent.
Embodiment 5：To the repellent activity of aphid under the compounds of this invention low concentration
The aptery adult aphid of more than 20 black peach aphids is discharged by liberation port, per arm Jing aspiration pumps with 0.2L/min be passed through Jing activated carbons and The humid air of distilled water.The humid air that test arm is imported first passes through 5 μ g sample odor sources, and another arm is led as control arm The humid air for entering first passes through solvent.Number of the aphid in each arm when record imports sample 15min.Often it is repeated once with anhydrous Ethanol purge olfactometer and leather hose, change filter paper and exchange two-arm and use, each sample experiments is repeated four times.Smelt with crossing Jue Yi centers 2cm is defined and counts treatment group or control group, and the aphid do not crossed is designated as unreacted group.
Corrected mortality is calculated, formula is as follows:
Scattering ratio=(control group borer population-treatment group borer population)/(control group borer population+treatment group borer population) * 100
Black peach aphid repellent activity test result is shown in Table 3
Repellent activity (5 μ g) of the Formulas I partial target compound of table 3 to black peach aphid
As a result show, the compound of the present invention has at low concentrations repellent activity, wherein compound I-2, I- to black peach aphid 6th, I-8, I-9, I-10, I-14, I-17, I-18 and I-25 under the dosage of 5 μ g to the suppression scattering ratio of black peach aphid more than 60%, It is green and the stability of compound I-2, I-6, I-8, I-9, I-10, I-14, I-17, I-18 and I-25 is higher than lead compound EBF Colour circle is protected, with the value further developed as the agent of aphid Behavior- Based control, with applications well prospect.
Embodiment 6：The compounds of this invention activity of resisting tobacco mosaic virus
Inactivation in vitro activity of resisting tobacco mosaic virus:Reagent agent is solved with phosphate buffer molten (0.01mol/L) The liquid containing 10mg/L TMV is made into afterwards, and with clear water as control, drug concentration is 100mg/L.5～8 leaf ages are inoculated in after 30min Tobacco leaf, often processes and is repeated 3 times, and in 24 DEG C, cultivates in the greenhouse of relative humidity 60% after 3～4d, counts blade withered spot number Measure and calculate preventive effect.
Protective effect activity of resisting tobacco mosaic virus:Tested from the tobacco seedling of 5～8 leaf phases, often processed 5mL cauline leafs Medicament (concentration is 100mg/L) is sprayed, 3 repetitions are set.TMV (concentration is 10mg/L), in 24 DEG C, phase are inoculated with after dispenser 24h To cultivating in the greenhouse of humidity 60% after 3～4d, count blade withered spot quantity and calculate preventive effect.
Therapeutic action activity of resisting tobacco mosaic virus:Carried out from the tobacco seedling of 5～8 leaf phases, inoculum density is 10mg/L 5mL cauline leafs are often processed after TMV, 24h and sprays medicament (concentration is 100mg/L), 3 repetitions are set, in 24 DEG C, relative humidity 60% Greenhouse in cultivate after 3～4d, statistics blade withered spot quantity simultaneously calculates preventive effect.
Preventive effect=(control group blade withered spot quantity-treatment group blade withered spot quantity)/(control group blade withered spot quantity) * 100
Activity of resisting tobacco mosaic virus test result is shown in Table 4
The Formulas I target compound activity of resisting tobacco mosaic virus of table 4
As a result show, the compound of the present invention is also respectively provided with certain anti-disease activity, wherein chemical combination to tobacco mosaic virus (TMV) Thing I-7, I-9, I-11, I-13, I-14, I-18, I-19, I-21, I-23, I-25, I-37, I-38, I-39 and I-40 exist Under the concentration of 100mg/L, the activity with resisting tobacco mosaic virus, it protects Zuo Yong ﹑ therapeutic actions and inactivation in vitro to live Property more than 30%, with the value developed as plant antiviral agent, economical and efficient environmental protection, with good application Prospect.
Embodiment 7：The compounds of this invention bactericidal activity
Bactericidal activity measure is carried out using mycelial growth rate method to target compound.
It is red for fusarium graminearum, Rhizoctonia solani Kuhn, botrytis cinerea pers, tomato early epidemic germ, tobacco for trying bacterial classification Star germ and cucumber anthracnose etc..
50mg target compounds are weighed respectively, then sample dimethyl sulfoxide is dissolved in into, and respectively constant volume is 5000mg/ into concentration The liquid of L is standby.
Take the liquid that 2mL concentration is 5000mg/L and potato dextrose agar (PDA) culture medium that 98mL melts to mix, Concentration is prepared into for the toxic culture medium 100mL of 50mg/L.Toxic culture medium is divided into into 4 parts, pour into respectively 4 it is a diameter of In the culture dish of 9cm, toxic PDA plate is made.After toxic culture medium condensation in ware, it is respectively connected to cultured a diameter of The pathogen bacteria cake of 0.5cm.It is placed in 25 DEG C of incubators and cultivates.Polyoxin B with same concentrations is as comparison medicament, and diformazan is sub- Sulfone is solvent control, while setting sterilized water as blank, 4 repetitions of each sample, above operation is sterile working.Treat sky After bacterium colony in white control fully grows, with the colony diameter that crossing method measures each process, its mean value is taken.
Calculated with the blank after correction and the bacterium colony average diameter for processing
Inhibiting rate=(control colony diameter-process colony diameter)/control colony diameter * 100
Bactericidal activity test result is shown in Table 5
The Formulas I target compound bactericidal activity of table 5
As a result show, the compound of the present invention has certain bactericidal activity, especially amide containing structure in Formulas I (X is N, Y is O) compound entirety bactericidal activity it is more obvious, particularly have significantly suppression to the red mildew bacterium ﹑ botrytis cinerea pers of little Mai System activity.Additionally, activity of the part of compounds such as I-17 of structure containing ester group (X is O, and Y is O) to Rhizoctonia solani Kuhn in Formulas I And I-20 projects (inhibiting rate is respectively 80% and 86%) to the activities present of fusarium graminearum, and with as bactericide one is entered The value of step exploitation.

Claims (11)

1. trans- (the β)-farnesene analog of salicylic acid, it is characterised in that the structural formula of the analog is shown in formula I：
Wherein R1For hydrogen, methyl, ethyl, phenyl or benzyl；R2For methyl, methoxyl group, chlorine, fluorine, trifluoromethyl；R3For hydrogen, first Base；X is oxygen, nitrogen；Y is oxygen.
2. a kind of preparation method of trans- (the β)-farnesene analog of salicylic acid described in claim 1, it is characterised in that system Preparation Method is comprised the following steps：
In the presence of dehydrating agent and condensing agent or acid binding agent, in organic solvent by geraniol, spiceleaf amine or replace spiceleaf amine with Compound shown in formula II carries out condensation reaction in the presence of catalyst, obtains the compound shown in Formulas I：
Wherein R1For hydrogen, methyl, ethyl, phenyl or benzyl；R2For methyl, methoxyl group, chlorine, fluorine, trifluoromethyl；Y is oxygen；
Work as R1When being hydrogen, methyl, ethyl, phenyl, type I compound synthesis is comprised the following steps：Salicylic acid is mixed with organic solvent Close, dehydrating agent and condensing agent or acid binding agent are then gradually added into successively, with geraniol or spiceleaf amine or replacement spiceleaf amine, catalyst And organic solvent mixing, condensation reaction is carried out, solvent is sloughed in decompression, and silica gel column chromatography is separated, and obtains the compound shown in formula I.
3. the preparation method of trans- (the β)-farnesene analog of salicylic acid according to claim 2, it is characterised in that work as R1 When being benzyl, type I compound synthesis is comprised the following steps：Salicylic acid is mixed with organic solvent, benzyl bromine or halogenated aryl hydrocarbon is added, Key intermediate substituted salicylic acid is obtained under phase transfer catalyst effect, dehydrating agent and condensing agent is then sequentially added or is tied up acid Agent, then mix with geraniol or spiceleaf amine or replacement spiceleaf amine, catalyst and organic solvent, condensation reaction is carried out, decompression is sloughed Solvent, silica gel column chromatography is separated, and obtains the compound shown in formula I.
4. the preparation method of trans- (the β)-farnesene analog of salicylic acid according to Claims 2 or 3, it is characterised in that The reaction temperature is -50 DEG C～200 DEG C.
5. the preparation method of trans- (the β)-farnesene analog of salicylic acid according to Claims 2 or 3, it is characterised in that The reaction temperature is 20 DEG C～50 DEG C.
6. the preparation method of trans- (the β)-farnesene analog of salicylic acid according to Claims 2 or 3, it is characterised in that： Organic solvent used include methyl alcohol, ethanol, normal propyl alcohol, isopropanol, benzene,toluene,xylene, acetonitrile, propionitrile, butyronitrile, acetone, Butanone, methylisobutylketone, N,N-dimethylformamide, DMAC N,N' dimethyl acetamide, N- methyl-formailide, N- methylpyrroles Alkanone, HMPA, dimethyl sulfoxide, petroleum ether, methyl acetate, ethyl acetate, ether, diisopropyl ether, ethylene glycol list Methyl ether, ethylene glycol monoethyl ether, diethylene glycol monomethyl ether, diethylene glycol monoethyl ether, glycol dimethyl ether, dichloromethane, chloroform, four At least one or more than one any combination in chlorination carbon, hexane, hexamethylene, tetrahydrofuran.
7. the preparation method of trans- (the β)-farnesene analog of salicylic acid according to Claims 2 or 3, it is characterised in that： Described dehydrating agent be dicyclohexylcarbodiimide, N, N- DICs, 1- (3- dimethylamino-propyls) -3- ethyls Carbodiimide one or more any combination；Condensing agent is N, N ＇-carbonyl dimidazoles；Catalyst is 4- dimethylamino pyrroles Pyridine；Acid binding agent is organic base or inorganic base, selected from piperidines, NaOH, potassium carbonate, pyridine, triethylamine, sodium carbonate, potassium carbonate, Sodium acid carbonate, saleratus, sodium methoxide, sodium hydride one or more any combination.
8. the preparation method of trans- (the β)-farnesene analog of salicylic acid according to claim 3, it is characterised in that：Institute The phase transfer catalyst stated is chain polyethylene glycol, chain dialkylethers, and 18 are preced with 6, cyclodextrin；Benzyl triethyl ammonium chlorine Change ammonium (TEBA), TBAB, tetrabutylammonium chloride, 4-butyl ammonium hydrogen sulfate (TBAB), tri-n-octyl methyl ammonium chloride, ten Dialkyl group trimethyl ammonium chloride, tetradecyl trimethyl ammonium chloride；One or more in pyridine, tri-n-butylamine, season phosphonium salt Any combination.
9. trans- (the β)-farnesene analog of salicylic acid described in a kind of claim 1 is the medicine of active component.
10. trans- (the β)-farnesene analog of salicylic acid described in a kind of claim 1 is prevented and treated in tobacco mosaic virus (TMV) (TMV) In purposes.
Application of trans- (the β)-farnesene analog of salicylic acid described in a kind of 11. claims 1 in terms of control of insect.
CN201510076763.9A 2015-02-12 2015-02-12 Salicylic acid trans-(beta)-farnesene analogues and application thereof Expired - Fee Related CN104693035B (en)

Priority Applications (2)

Application Number Priority Date Filing Date Title
CN201510076763.9A CN104693035B (en) 2015-02-12 2015-02-12 Salicylic acid trans-(beta)-farnesene analogues and application thereof
PCT/CN2016/000006 WO2016127723A1 (en) 2015-02-12 2016-01-05 Salicylic acid trans-(β)-farnesene analogues and uses thereof

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201510076763.9A CN104693035B (en) 2015-02-12 2015-02-12 Salicylic acid trans-(beta)-farnesene analogues and application thereof

Publications (2)

Publication Number Publication Date
CN104693035A CN104693035A (en) 2015-06-10
CN104693035B true CN104693035B (en) 2017-05-10

Family

ID=53340633

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201510076763.9A Expired - Fee Related CN104693035B (en) 2015-02-12 2015-02-12 Salicylic acid trans-(beta)-farnesene analogues and application thereof

Country Status (2)

Country Link
CN (1) CN104693035B (en)
WO (1) WO2016127723A1 (en)

Families Citing this family (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104693035B (en) * 2015-02-12 2017-05-10 中国农业大学 Salicylic acid trans-(beta)-farnesene analogues and application thereof
CN105294495A (en) * 2015-09-21 2016-02-03 苏州大学 Preparation method of cyanomethyl ester
CN105439861B (en) * 2015-12-03 2018-04-06 北京工商大学 One kind drop ambergris leaf ester aphid controlling agent
CN105418449A (en) * 2015-12-15 2016-03-23 中国船舶重工集团公司第七二五研究所 Phenolic amide type anti-fouling agents containing benzene ring with methoxyl and preparation method of phenolic amide type anti-fouling agents
CN106496030B (en) * 2016-10-09 2018-11-23 湖北中烟工业有限责任公司 The preparation method and applications of the latent fragrant monomer P-methoxybenzoic acid esters of cigarette
CN111494647A (en) * 2020-05-08 2020-08-07 牡丹江医学院附属红旗医院 A pharmaceutical composition for treating cataract and its preparation method

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6333432B1 (en) * 1999-05-04 2001-12-25 Gina M. Fitzpatrick Fungicidal compositions and methods, and compounds and methods for the preparation thereof
WO2013157926A1 (en) * 2012-04-19 2013-10-24 Nyken Holding B.V. Geranyl geranyl acetone analogs and uses thereof
CN104693035B (en) * 2015-02-12 2017-05-10 中国农业大学 Salicylic acid trans-(beta)-farnesene analogues and application thereof

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
RN:1026625-55-7;ACS;《STN REGISTRY》;20080608;第16页 *

Also Published As

Publication number Publication date
WO2016127723A1 (en) 2016-08-18
CN104693035A (en) 2015-06-10

Similar Documents

Publication Publication Date Title
CN104693035B (en) Salicylic acid trans-(beta)-farnesene analogues and application thereof
CN105153113B (en) 3,5-dihalo Aminothiocarbonylbenzene insecticides
CN107848959A (en) The phenoxyphenylamidineand of halogen substitution and its purposes as fungicide
CN106167484B (en) Pyrimidine-containing substituted pyrazole compound and preparation method and application thereof
CN108271339A (en) Seed endophyte, compositions related and its application method between cultivar and species
CN101491242B (en) Application technique of dimethyl disulfide as soil fumigant
KR20020058089A (en) Pyrazolecarboxamide and pyrazolethioamide as fungicide
CN109689644B (en) Pyridazinone compound and application thereof
JP2009509944A (en) Molecular modification of biogenic compounds and their application to weeding
CN101928272A (en) 3-o-methylphenyl-2-oxo-1-oxaspiro[4,5]-decyl-3-alkene-4-ol derivative
CN107382848A (en) A kind of nicotinamide compounds and its preparation method and application
TW201031334A (en) Use of sulphur-containing heteroaromatic acid analogues
CN106117064B (en) A kind of (anti-)-β-farnesene analog of acid groups containing jasmine and its preparation and application
CN108191786B (en) 2, 5-substituent-1, 3, 4-oxadiazole disulfone derivative, preparation method and application thereof
ES2352323T3 (en) (-) - OPTICALLY PURE CLETODIM, COMPOSITIONS AND METHODS TO CONTROL THE GROWTH OF PLANTS THAT INCLUDE THE SAME.
CN114805219B (en) Fluorine-containing pyrimidine diether compound and application thereof
CN104334533B (en) 5 halo-pyrazole biphenyl carboxamides
CN100594785C (en) Controlling plant pathogens and pests with applied or induced auxins
CN108191665A (en) Eugenol ester analog and preparation method thereof and insecticide
CN104829555B (en) Containing 1,2,3 thiadiazoles group (anti-) β farnesene analogs and preparation method and application
BR102013027162A2 (en) Metal complexes and naringin and naringenin and insecticidal compositions for the control of urban, agricultural and forestry insect pests
CN108117528B (en) 2, 5-substituent-1, 3, 4-oxadiazole sulfone derivative, preparation method and application thereof
CN108794461B (en) Fluorine-containing phenyl oxadiazole pyrazole insecticidal bactericide
CN110759864A (en) Genipin lactam derivatives and preparation and application thereof
CN115043838B (en) Quinolone-lixivium alkaloid and preparation method and application thereof

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant
CF01 Termination of patent right due to non-payment of annual fee
CF01 Termination of patent right due to non-payment of annual fee

Granted publication date: 20170510