CN113461836A - Application of amino acid cyclodextrin derivative as pesticide synergist - Google Patents
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Abstract
The invention discloses application of an amino acid cyclodextrin derivative as a pesticide synergist. The amino acid cyclodextrin derivative is obtained by nucleophilic substitution reaction of amino acid or amino acid ester and mono-6-O- (p-toluenesulfonyl) -beta-cyclodextrin under alkaline conditions, and is safe, non-toxic and low in manufacturing cost; the amino acid cyclodextrin derivative is complexed with the active ingredients of the pesticide, so that the solubility of the pesticide can be improved, and a synergistic effect is achieved; therefore, the pesticide synergist can be used as a pesticide synergist, solves the problems of low solubility and poor pesticide effect of part of pesticides, has the effects of improving the pesticide effect of the pesticides and relieving the generation of pesticide resistance of pests, can provide candidate auxiliaries for development and improvement of efficient pesticide preparations, and is beneficial to realization of reduction and synergism of pesticides.
Description
Technical Field
The invention belongs to the technical field of pesticides, and particularly relates to an application of an amino acid cyclodextrin derivative as a pesticide synergist.
Background
Some insect pests affect the growth of crops during the whole growth process of the crops, and chemical agents are the most effective method for preventing insects. However, many agricultural pesticides are themselves almost insoluble in water, and are mostly dissolved in organic solvents. Along with the use of a large amount of pesticides, the pollution to the environment is not negligible, and according to statistics, in the use process of the conventional pesticides, about 80 percent of the pesticides directly enter the environment, so that the natural enemies of pests or other beneficial insects are greatly reduced, water body pollution, land pollution and environment pollution are caused; the improper use of the pesticide causes the accumulation of a large amount of harmful substances in agricultural products, the quality and the safety of the agricultural products are seriously affected, and the polluted agricultural products can cause the reduction of the immunity of the organism, gastrointestinal diseases, cancers, cardiovascular diseases and even genetic deformity after being eaten.
Therefore, on the premise of not reducing the crop yield, the method for reducing the pesticide consumption by improving the pesticide effect of the existing pesticide is an effective method for improving the pesticide residue pollution. The current research found that the formation of cyclodextrin inclusion complexes is one of the solutions to this problem.
Supramolecular Cyclodextrins (Cyclodextrins) are cyclic maltooligosaccharides formed by the polymerization of D-glucopyranose units through alpha-1, 4-glycosidic bonds, obtained by bioconversion of starch. The common types of the cyclodextrin are alpha-, beta-and gamma-3, wherein the beta-cyclodextrin is most applied and is a good embedding agent in various industries such as medicine and the like. Cyclodextrins are currently widely used in food, medicine, cosmetics, and agriculture. Because of its special structural morphology, cyclodextrin is called molecular capsule, and cyclodextrin is used for studying the nature of molecular recognition and inclusion in aqueous solution, self-assembly of molecules, and the like, and is one of the hot fields of cyclodextrin chemistry at present.
Patent CN102060941 reports the preparation of similar compounds, whose chemical structure is shown below:
wherein: a is one of 0,1,2,3,4,5,6,7 or 8; b is one of 1,2,3,4,5,6,7,8 or 9; a + b is one of 6,7,8 or 9; f is one of 0,1 or 2; r1Is (C)1-C6) Alkylene, optionally substituted by 1 to 2 CH3A radical, 1 to 2 OH groups or (CH)2)v-phenylene- (CH)2)k-substitution, wherein v is one of 0,1,2,3 or 4, k is one of 0,1,2,3 or 4; r2、R3is-H, formyl, acetyl, methyl, ethyl, acetoxy, benzyloxycarbonyl, t-butoxycarbonyl, fluorenylmethoxycarbonyl, -CH2COOM and hydroxyphenyl, and the substituents may be the same or different; m is-H, NH4Or alkali metal ions. The compound structure mainly relates to 6-deoxy thioether alpha-amino acid derivative cyclodextrin, 6-deoxy sulfoxide alpha-amino acid derivative, 6-deoxy sulfone alpha-amino acid derivative cyclodextrin, a preparation method thereof and application thereof in preparing medicines with muscle relaxation antagonism.
The use of cyclodextrins as agrochemical delivery systems for increasing biological activity is reported in patent WO2019215645, but said compounds do not contain substitutions of amino acid structures in their structure.
Patent WO 2017045904 relates to a method for controlling resistant insects, wherein the resistant insects are treated with a cyclodextrin complex, characterized in that the cyclodextrin complex is a complex with an insecticidally active substance. However, the structure of the cyclodextrin compound does not contain a substituent of an amino acid structure.
Patent CN101362807A reports preparation of similar compounds, but the reaction steps are complicated, and the method is that iodo-cyclodextrin is synthesized, and then amino acid is condensed with iodo-cyclodextrin in the presence of base to obtain amino acid cyclodextrin derivative. The amino acid is any one of histidine, tryptophan, phenylalanine, tyrosine, methionine and cysteine; the cyclodextrin is beta-cyclodextrin, and an organic solvent N, N-dimethylformamide is used as a solvent in the reaction process.
Disclosure of Invention
The invention provides a pesticide synergist which takes amino acid cyclodextrin derivatives as a pesticide, and is a green and environment-friendly pesticide auxiliary agent for improving pesticide effect and reducing potential pollution.
The invention provides a cyclodextrin derivative, in particular to an application of an amino acid cyclodextrin derivative as a synergist of an agricultural insecticide, and provides a thought and a method which have the advantages of easily available raw materials for production, stable preparation process, high yield, environmental protection, safety, no toxicity and capability of effectively improving the effect of a pesticide.
Therefore, the first purpose of the invention is to provide an amino acid cyclodextrin derivative, the structural formula of which is shown in formula I,
wherein: n is 0 or 1; r1 is hydrogen, methyl, -CH2OH、-CH(CH3)2、-CH(CH3)CH2CH3Benzyl, indolyl or methylene-phenol; r2 is hydrogen, methyl or ethyl.
The invention also provides a preparation method of the amino acid cyclodextrin derivative, which comprises the following steps:
s1, adding beta-cyclodextrin into water with the mass being 20-30 times that of the beta-cyclodextrin to dissolve the beta-cyclodextrin, adding paratoluensulfonyl chloride into a beta-cyclodextrin water solution according to the mass ratio of the beta-cyclodextrin to the paratoluensulfonyl chloride being 1: 1-1.5, stirring and reacting for 6-8 hours, adding a sodium hydroxide water solution with the mass fraction being 10% and being 0.2 times that of water in the solution, continuously stirring the obtained suspension for 15-30 minutes, filtering to remove insoluble substances, collecting filtrate, and adjusting the pH value of the filtrate to 8-8.5 by using ammonium chloride; then standing for 10-15 hours at 4 ℃, filtering, separating out white solid, washing with deionized water, recrystallizing with distilled water at 50-80 ℃ to obtain bright white flaky crystals, and freeze-drying to obtain 6-position mono-substituted cyclodextrin sulfonate;
s2, adding 6-site mono-substituted cyclodextrin sulfonate prepared in S1 and amino acid or amino acid ester into a solvent mixed by triethanolamine and water according to the volume ratio of 1:1.2-1.5, and stirring for dissolving; gradually heating to 85-100 ℃, stirring and reacting for 24-48 hours at the temperature, and carrying out reduced pressure rotary evaporation to remove most of the solvent in the reaction solution; and gradually dripping the reaction solution into stirred acetone or ethanol, refrigerating, filtering, collecting solids, removing unreacted amino acid or amino acid ester, and drying in vacuum at 40-45 ℃ to obtain the mono- (6-L-amino acid-6-deoxy) -beta-cyclodextrin or the mono- (6-L-amino acid ester-6-deoxy) -beta-cyclodextrin, namely the amino acid cyclodextrin derivative.
Preferably, the amino acid is L-serine or beta-aminopropionic acid, and the amino acid ester is glycine methyl ester.
The invention also provides application of the amino acid cyclodextrin derivative as a pesticide synergist.
The invention also provides a pesticide composition which contains the amino acid cyclodextrin derivative and a pesticide.
The invention also provides a preparation method of the clathrate compound of the amino acid cyclodextrin derivative and the pesticide, which comprises the following steps:
dissolving the amino acid cyclodextrin derivative in water, and continuously stirring until a saturated solution is formed; dissolving a pesticide in a proper amount of cosolvent, then dropwise adding the pesticide solution into the amino acid cyclodextrin derivative saturated solution to form a mixed solution, continuously stirring and reacting for 18-48 hours, cooling the mixed solution to 4 ℃, standing, after the precipitate is completely separated out, carrying out suction filtration, washing the precipitate with water and ethanol, and carrying out vacuum drying to prepare the amino acid cyclodextrin derivative and pesticide clathrate compound.
Preferably, the amount ratio of the amino acid cyclodextrin derivative to the pesticide in the mixed solution is 3: 1-3.
Preferably, the pesticide is an insecticide.
More preferably, the pesticide is indoxacarb, pyraoxystrobin and/or chlorfenapyr.
Preferably, the stirring reaction temperature is 50 ℃.
The amino acid cyclodextrin derivative is mono- (6-L-amino acid (ester) -6-deoxy) -beta-cyclodextrin, has stronger binding force and selectivity to pesticide, and improves the pesticide effect of commercial pesticide.
Compared with the prior art, the invention has the following technical effects: the invention provides an agricultural amino acid cyclodextrin derivative synergist, which takes an amino acid cyclodextrin derivative as a synergist, water as a solvent and a simple organic solvent as a cosolvent, and is mixed with a pesticide insecticide, so that the water solubility and the stability of the pesticide can be effectively improved, the insecticidal activity of the pesticide is improved, and the pesticide dosage is reduced.
The amino acid cyclodextrin derivative is obtained by nucleophilic substitution reaction of amino acid or amino acid ester and mono-6-O- (p-toluenesulfonyl) -beta-cyclodextrin under alkaline conditions, and is safe, non-toxic and low in manufacturing cost; the amino acid cyclodextrin derivative is complexed with the active ingredients of the pesticide, so that the solubility of the pesticide can be improved, and a synergistic effect is achieved; therefore, the pesticide synergist can be used as a pesticide synergist, solves the problems of low solubility and poor pesticide effect of part of pesticides, has the effects of improving the pesticide effect of the pesticides and relieving the generation of pesticide resistance of pests, can provide candidate auxiliaries for development and improvement of efficient pesticide preparations, and is beneficial to realization of reduction and synergism of pesticides.
The amino acid cyclodextrin derivative can improve the solubility of active ingredients of the insecticide, has high safety and strong stability, has obvious synergistic effect on preventing and controlling lepidoptera larvae after being complexed with the active ingredients of the insecticide, reduces the environmental pollution, simultaneously reduces the production and use cost, and also has the characteristics of easily obtained reaction raw materials and low production cost.
Detailed Description
The following examples are further illustrative of the present invention and are not intended to be limiting thereof.
The preparation method of the amino acid-cyclodextrin derivative comprises the following steps:
1) adding beta-cyclodextrin into deionized water according to the mass ratio of 1: 20-30 for dissolving; adding p-toluenesulfonyl chloride into a beta-cyclodextrin aqueous solution according to the mass ratio of the beta-cyclodextrin to the p-toluenesulfonyl chloride of 1: 1-1.5, stirring and reacting at 25 ℃ for 6-8 hours, adding a sodium hydroxide aqueous solution with the mass fraction of 10% according to the mass ratio of solvent deionized water to the sodium hydroxide aqueous solution of 1:0.2 in the solution, continuously stirring the obtained suspension for 15-30 minutes, filtering to remove insoluble substances, collecting filtrate, and adjusting the pH value of the filtrate to 8-8.5 by using ammonium chloride; standing the solution at 4 ℃ for 10-15 hours, filtering, separating out a white solid, washing with deionized water for three times, and recrystallizing with distilled water for three times at 50-80 ℃ to obtain a bright white flaky crystal; freeze drying to obtain 6-site monosubstituted cyclodextrin sulfonate;
2) adding 6-position mono-substituted cyclodextrin sulfonate and amino acid (ester) into a solvent formed by mixing deionized water and triethanolamine in a volume ratio of 1:0.6-0.8 according to a mass ratio of 1: 3-5, and stirring for dissolving; gradually heating to 85-100 ℃, stirring and reacting for 24-48 hours at the temperature, and carrying out reduced pressure rotary evaporation at 40-45 ℃ to remove most of the solvent; gradually dripping the reaction solution into the stirred acetone or absolute ethyl alcohol, stirring, refrigerating and filtering; and (3) dissolving the solid obtained by collecting the filter cake in water, filtering to remove insoluble substances, dropwise adding the obtained solution into acetone or absolute ethyl alcohol again to obtain a precipitate (the process can be repeated for three times to remove unreacted amino acid (ester)), and drying the precipitate in vacuum at the temperature of between 40 and 45 ℃ to obtain the mono- (6-L-amino acid (ester) -6-deoxy) -beta-cyclodextrin.
The preparation method of the cyclodextrin inclusion compound of the insecticide provided by the invention comprises the following steps:
1. a certain amount of the amino acid cyclodextrin derivative of the present invention is added to a double-necked bottle, and a proper amount of deionized water is added.
2. Stirring and dissolving at a certain temperature (room temperature-70 ℃) to ensure that the amino acid cyclodextrin derivative solution in the step 1 is a saturated solution.
3. And weighing pesticide raw medicines which are in a certain proportion with the amino acid cyclodextrin derivative (the mass ratio of the amino acid cyclodextrin derivative to the pesticide is 3: 1-3), and dissolving the pesticide raw medicines into a small amount of acetone solution.
4. The insecticide acetone solution is slowly dropped into the saturated aqueous solution of the amino acid cyclodextrin derivative while stirring to form a mixed solution.
5. Amino acid cyclodextrin derivative inclusion: and (4) stirring the mixed solution in the step (4) for 18-48 hours under a certain temperature condition.
6. Then standing and cooling to 4 ℃ to ensure that the precipitate is completely separated out, carrying out suction filtration, washing the precipitate with water and ethanol, and drying to obtain the clathrate compound.
The present invention will be further described with reference to the following examples.
Example 1
Beta-cyclodextrin (4.0g, 3.54mmol) was weighed, 100mL of deionized water was added to the reaction flask, and the mixture was stirred well to form a milky white suspension. P-toluenesulfonyl chloride (TsCl), 1.0g, was carefully added in portions and stirred vigorously at room temperature for 6 h. Then 16mL of a 2.5mol/L NaOH solution was added dropwise to the flask over 15 minutes, and insoluble matter was filtered. Adding 3.94g of ammonium chloride solid into the filtrate to adjust the pH of the filtrate, fully and uniformly mixing, then placing the mixture in a refrigerator for refrigeration at 4 ℃, standing overnight, generating a large amount of white precipitate, performing suction filtration and collecting the precipitate. Filtering to obtain white solid, recrystallizing with distilled water for 2 times, and freeze drying to obtain white solid 0.92g with yield 20.39%. The measured characterization data are:1h NMR (600MHz, Deuterium Oxide) δ 7.75(d, J ═ 8.0Hz,2H),7.44(d, J ═ 8.0Hz,2H), 5.95-5.57 (m,14H), 4.96-4.64 (m,7H), 4.58-4.13 (m,6H), 3.80-3.41 (m,35H),2.43(s,3H), and this compound was named CD-1.
Example 2
Weighing dried CD-1(2g, 1.55mmol) and L-serine (0.56g, 5.4mmol), adding into a round-bottom flask, mixing triethanolamine and deionized water at a volume ratio of 1:1.5, adding 25mL into a reaction bottle, gradually heating to 85 deg.C, condensing under reflux, protecting with nitrogen,and (4) mechanically stirring. After 24 hours of reaction, the reaction solution was cooled to room temperature and then most of the solvent was distilled off under reduced pressure. The reaction solution was gradually added dropwise to the stirred absolute ethanol, and then refrigerated overnight in a refrigerator at 4 ℃ and filtered to obtain a pale yellow solid. Dissolving the filter cake in a small amount of water, filtering to remove insoluble substances, then dropwise adding into absolute ethyl alcohol again, refrigerating again, and vacuum drying the solid obtained by filtering at 45 ℃ to obtain serine-beta-cyclodextrin (CD-2), wherein the characterization data is as follows:1H NMR(600MHz,Deuterium Oxide)δ5.06(d,J＝3.8Hz,7H),3.99–3.74(m,33H),3.68–3.53(m,14H)。
example 3
Weighing dried CD-1(2g, 1.55mmol) and beta-aminopropionic acid (0.48g, 5.4mmol), adding into a round-bottom flask, fully mixing triethanolamine and deionized water according to the volume ratio of 1:1.5, adding 25mL into a reaction bottle, gradually heating to 100 ℃, condensing and refluxing under nitrogen protection, and mechanically stirring. After 24 hours of reaction, the reaction solution was cooled to room temperature and then most of the solvent was distilled off under reduced pressure. The reaction solution was gradually added dropwise to the stirred absolute ethyl alcohol, and then refrigerated overnight in a refrigerator at 4 ℃, filtered, and washed with a small amount of water and absolute ethyl alcohol to obtain a pale yellow solid. Dissolving the filter cake in a small amount of water, filtering to remove insoluble substances, then dropwise adding into absolute ethyl alcohol again, refrigerating again, and vacuum drying the solid obtained by filtering at 45 ℃ to obtain beta-alanine-beta-cyclodextrin (CD-3), wherein the characterization data is as follows:1H NMR(600MHz,Deuterium Oxide)δ5.07(d,J＝4.1Hz,7H),4.13–3.49(m,42H),3.17(t,2H),2.54(t,2H)。
example 4
Weighing dried CD-1(2g, 1.55mmol) and glycine methyl ester (1g, 7.9mmol), adding into a round-bottom flask, mixing triethanolamine and deionized water at a volume ratio of 1:1.5, and collecting 25Adding the mL into a reaction bottle, gradually heating to 100 ℃, condensing and refluxing, protecting with nitrogen, and mechanically stirring. After 24 hours of reaction, the reaction solution was cooled to room temperature and then most of the solvent was distilled off under reduced pressure. The reaction solution was gradually added dropwise to the stirred absolute ethyl alcohol, and then refrigerated overnight in a refrigerator at 4 ℃, filtered, and washed with a small amount of water and absolute ethyl alcohol to obtain a pale yellow solid. Dissolving the filter cake in a small amount of water, filtering to remove insoluble substances, then dropwise adding into absolute ethyl alcohol again, refrigerating again, and vacuum drying the solid obtained by filtering at 45 ℃ to obtain glycine methyl ester-beta-cyclodextrin (CD-4), wherein the characterization data is as follows:1H NMR(600MHz,Deuterium Oxide)δ5.07(d,J＝4.1Hz,7H),4.13–3.49(m,47H)。
example 5: preparation of indoxacarb-based beta-cyclodextrin inclusion compound
Beta-cyclodextrin (240mg, 0.2mmol) prepared in example 3 was placed in deionized water (4mL) and introduced into a two-necked flask with a cooler and nitrogen outlet at 50 deg.C, and the solution was stirred at 50 deg.C for a period of time until the solution was saturated. An acetone solution (2mL) containing indoxacarb (104mg, 0.2mmol) was then slowly added dropwise to a saturated solution of beta-aminopropionic acid-beta-cyclodextrin at 50 deg.C to form a mixture. And continuously stirring the mixture at 50 ℃ for 24 hours, cooling the mixture to 4 ℃ while stirring, standing for 3 hours to completely separate out a precipitate, performing suction filtration, washing the precipitate with water and ethanol, and drying to obtain the indoxacarb-based beta-aminopropionic acid-beta-cyclodextrin inclusion compound.
Example 6: preparation of indoxacarb-based serine-beta-cyclodextrin inclusion compound
Serine- β -cyclodextrin (242mg, 0.2mmol) prepared in example 2 was placed in deionized water (4mL) and introduced into a two-necked flask with a cooler and nitrogen outlet at 50 ℃ and the solution was stirred for a period of time at 50 ℃ until the solution was saturated. An acetone solution (2mL) containing indoxacarb (104mg, 0.2mmol) was then slowly added dropwise to a saturated solution of serine- β -cyclodextrin at 50 ℃ to form a mixture. And continuously stirring the mixture at 50 ℃ for 24 hours, cooling the mixture to 4 ℃ while stirring, standing for 3 hours to completely separate out a precipitate, performing suction filtration, washing the precipitate with water and ethanol, and performing vacuum drying to obtain the serine-beta-cyclodextrin inclusion compound based on the indoxacarb.
Example 7: preparation of pyraoxystrobin-based beta-cyclodextrin inclusion compound
Beta-cyclodextrin (242mg, 0.2mmol) prepared in example 3 was placed in distilled water (4mL) and introduced into a two-necked flask with a cooler and nitrogen outlet at 50 deg.C, and the solution was stirred at 50 deg.C for a period of time until the solution was saturated. An acetone solution (2mL) containing pyraoxystrobin (108mg, 0.2mmol) was then slowly added dropwise to a saturated solution of beta-alanine-beta-cyclodextrin at 50 ℃ to form a mixture. And continuously stirring the mixture at 50 ℃ for 24 hours, cooling the mixture to 4 ℃ while stirring, standing for 3 hours to completely separate out a precipitate, performing suction filtration, washing the precipitate with water and ethanol, and performing vacuum drying to obtain the betaaminopropionic acid-beta-cyclodextrin inclusion compound based on the pyraoxystrobin.
Example 8: preparation of Azole-ester-based serine-beta-cyclodextrin inclusion compounds
Serine- β -cyclodextrin (242mg, 0.2mmol) prepared in example 2 was placed in distilled water (4mL), introduced into a two-necked flask equipped with a cooler and a nitrogen outlet at 50 ℃ and the solution was stirred at 50 ℃ for a while until the solution was saturated. An acetone solution (2mL) containing carfentrazone-ethyl (108mg, 0.2mmol) was then slowly added dropwise to a saturated solution of serine- β -cyclodextrin at 50 ℃ to form a mixture. And continuously stirring the mixture at 50 ℃ for 24 hours, cooling the mixture to 4 ℃ while stirring, standing for 3 hours to completely separate out a precipitate, performing suction filtration, washing the precipitate with water and ethanol, and performing vacuum drying to obtain the serine-beta-cyclodextrin inclusion compound based on the pyraoxystrobin.
Example 9: preparation of chlorfenapyr-based beta-aminopropionic acid-cyclodextrin inclusion compound
Beta-cyclodextrin (240mg, 0.2mmol) prepared in example 3 was placed in distilled water (4mL) and introduced into a two-necked flask with a cooler and nitrogen outlet at 50 deg.C, and the solution was stirred at 50 deg.C for a period of time until the solution was saturated. An acetone solution (2mL) containing chlorfenapyr (81mg, 0.2mmol) was then slowly added dropwise to a saturated solution of beta-aminopropionic acid-beta-cyclodextrin at 50 deg.C to form a mixture. And continuously stirring the mixture at 50 ℃ for 24 hours, cooling the mixture to 4 ℃ while stirring, standing for 3 hours to completely separate out a precipitate, performing suction filtration, washing the precipitate with water and ethanol, and performing vacuum drying to obtain the beta-aminopropionic acid-beta-cyclodextrin inclusion compound based on the chlorfenapyr.
Example 10: preparation of Chlorfenapyr-based serine-beta-cyclodextrin inclusion Compound
Serine- β -cyclodextrin (242mg, 0.2mmol) prepared in example 2 was placed in distilled water (4mL), introduced into a two-necked flask equipped with a cooler and a nitrogen outlet at 50 ℃ and the solution was stirred at 50 ℃ for a while until the solution was saturated. An acetone solution (2mL) containing chlorfenapyr (81mg, 0.2mmol) was then slowly added dropwise to a saturated solution of serine- β -cyclodextrin at 50 ℃ to form a mixture. And continuously stirring the mixture at 50 ℃ for 24 hours, cooling the mixture to 4 ℃ while stirring, standing for 3 hours to completely separate out a precipitate, performing suction filtration, washing the precipitate with water and ethanol, and performing vacuum drying to obtain the chlorfenapyr-based serine-beta-cyclodextrin inclusion compound.
Effect test:
the poisoning effect of the above-prepared formulation of example 5 (indoxacarb-based beta-cyclodextrin inclusion complex of beta-aminopropionic acid), of example 7 (pyraclostrobin-based beta-cyclodextrin inclusion complex of beta-aminopropionic acid), of example 9 (chlorfenapyr-based beta-cyclodextrin inclusion complex of beta-aminopropionic acid) on Plutella xylostella (Linnaeus), Spodoptera exigua Hiibner (Spodoptera exigua) is demonstrated below by tests.
In all the following tests, the concentration (or amount) refers to the concentration (or amount) of the active substance pesticide.
Comparative formulations used in the following tests:
(1) the indoxacarb/hydroxypropyl-beta-cyclodextrin inclusion compound is prepared by the following method: the indoxacarb/hydroxypropyl-beta-cyclodextrin inclusion compound was prepared by taking hydroxypropyl-beta-cyclodextrin and indoxacarb (substance amount ratio 1: 1) according to the preparation method of example 5.
(2) The pyraoxystrobin/hydroxypropyl-beta-cyclodextrin inclusion compound is prepared by the following method: an azolidinium ester/hydroxypropyl- β -cyclodextrin inclusion compound was prepared by taking hydroxypropyl- β -cyclodextrin and azolidinium ester (substance amount ratio 1: 1) according to the preparation method of example 7.
(3) The chlorfenapyr/hydroxypropyl-beta-cyclodextrin inclusion compound is prepared by the following method: taking hydroxypropyl-beta-cyclodextrin and chlorfenapyr (the mass ratio of the substances is 1: 1), and preparing the chlorfenapyr/hydroxypropyl-beta-cyclodextrin inclusion compound according to the preparation method of the example 9.
1. Indoor toxicity test
1) The toxicity of the original drug and the preparation of the corresponding embodiment on the indoor plutella xylostella is determined by adopting a leaf soaking method, the original drug (indoxacarb, pyraoxystrobin or chlorfenapyr) and the preparation of the corresponding embodiment or a comparison preparation are dissolved in a proper amount of dimethyl sulfoxide, and 0.1% of tween water is selected for diluting to the corresponding concentration. Randomly selecting more than 10 plutella xylostella as one repeat from the plutella xylostella with consistent growth, wherein each treatment group has 3 repeats; the number of the survival plutella xylostella is counted at 24 hours and 48 hours after the treatment, and the death rate is calculated.
The action effect is as follows:
TABLE 1 synergistic effect of amino acid cyclodextrin derivatives on indoxacarb Plutella xylostella killing Activity
TABLE 2 synergistic effect of amino acid cyclodextrin derivatives on the Plutella xylostella killing Activity of Azole
TABLE 3 synergistic effect of amino acid cyclodextrin derivatives on Chlorfenapyr Plutella xylostella killing Activity
2) The toxicity of the original drug and the preparation of the corresponding embodiment on the indoor spodoptera exigua is determined by adopting a leaf soaking method, the original drug (indoxacarb, pyraoxystrobin or chlorfenapyr) and the preparation of the corresponding embodiment or a comparison preparation are dissolved in a proper amount of dimethyl sulfoxide, and 0.1% of tween water is selected to be diluted to a corresponding concentration. Randomly selecting more than 10 beet noctuids from beet noctuids with consistent growth as a repeat, wherein each treatment group has 3 repeats; the number of surviving beet armyworms was counted at 24 hours and 48 hours after the treatment, respectively, and the mortality was calculated.
The action effect is as follows:
TABLE 4 synergistic effect of amino acid cyclodextrin derivatives on indoxacarb beet armyworm killing Activity
TABLE 5 synergistic effect of amino acid cyclodextrin derivatives on Trichophyton sp
TABLE 6 synergistic Effect of amino acid Cyclodextrin derivatives on Chlorfenapyr beet armyworm killing Activity
2. Test of field drug effect
The field efficacy test is carried out in the cabbage heart where the diamondback moth occurs seriously in the flower city district of Guangzhou, Guangdong province. Test protocol: a cell is designed in a random block mode in each field, the cell is divided into 30 areas on average, and planting conditions of each area are as consistent as possible. And 6 medicaments are processed by each medicament, the population base numbers of the insects in each cell are respectively counted before the medicaments are applied, the residual population numbers of the insects in each cell are respectively investigated 3d, 5d and 7d after the medicaments are applied, the reduction rate of the insects in each cell is counted, and the relative prevention effect is calculated.
TABLE 7 field test results of pesticide spraying method for preventing and treating plutella xylostella
| Medicament | Effective component (g/mu) | The control effect of the pesticide is applied for 3 days% | The control effect is improved after 5 days of pesticide application | The control effect is 7 days after the pesticide is applied |
| Example 5 formulations | 30 | 85.92 | 88.0.3 | 85.21 |
| Example 7 formulations | 30 | 81.88 | 79.71 | 80.43 |
| Example 9 formulations | 30 | 76.67 | 79.17 | 74.17 |
| Indoxacarb emulsifiable concentrate | 30 | 70.85 | 80 | 78.33 |
| Pyraoxystrobin missible oil | 30 | 72.80 | 68.8 | 70.40 |
| Chlorfenapyr emulsifiable concentrate | 30 | 67.67 | 66.92 | 66.17 |
According to effect tests, the three insecticides and the amino acid cyclodextrin derivative form inclusion compounds, so that the three insecticides have good control effects on diamondback moth larvae and beet armyworm larvae, and the pesticide effect can be remarkably improved.
Claims (10)
1. A kind of amino acid cyclodextrin derivatives is characterized in that the structural formula is shown as formula I,
wherein: n is 0 or 1; r1 is hydrogen, methyl, -CH2OH、-CH(CH3)2、-CH(CH3)CH2CH3Benzyl, indolyl or methylene-phenol; r2 is hydrogen, methyl or ethyl.
2. A method for producing the amino acid cyclodextrin derivative of claim 1, comprising the steps of:
s1, adding beta-cyclodextrin into water with the mass being 20-30 times that of the beta-cyclodextrin to dissolve the beta-cyclodextrin, adding paratoluensulfonyl chloride into a beta-cyclodextrin water solution according to the mass ratio of the beta-cyclodextrin to the paratoluensulfonyl chloride being 1: 1-1.5, stirring and reacting for 6-8 hours, adding a sodium hydroxide water solution with the mass fraction being 10% and being 0.2 times that of water in the solution, continuously stirring the obtained suspension for 15-30 minutes, filtering to remove insoluble substances, collecting filtrate, and adjusting the pH value of the filtrate to 8-8.5 by using ammonium chloride; then standing for 10-15 hours at 4 ℃, filtering, separating out white solid, washing with deionized water, recrystallizing with distilled water at 50-80 ℃ to obtain bright white flaky crystals, and freeze-drying to obtain 6-position mono-substituted cyclodextrin sulfonate;
s2, adding 6-site mono-substituted cyclodextrin sulfonate prepared in S1 and amino acid or amino acid ester into a solvent mixed by triethanolamine and water according to the volume ratio of 1:1.2-1.5, and stirring for dissolving; gradually heating to 85-100 ℃, stirring and reacting for 24-48 hours at the temperature, and carrying out reduced pressure rotary evaporation to remove most of the solvent in the reaction solution; and gradually dripping the reaction solution into stirred acetone or ethanol, refrigerating, filtering, collecting solids, removing unreacted amino acid or amino acid ester, and drying in vacuum at 40-45 ℃ to obtain the mono- (6-L-amino acid-6-deoxy) -beta-cyclodextrin or the mono- (6-L-amino acid ester-6-deoxy) -beta-cyclodextrin, namely the amino acid cyclodextrin derivative.
3. The method according to claim 2, wherein the amino acid is L-serine or beta-aminopropionic acid, and the amino acid ester is glycine methyl ester.
4. Use of the amino acid cyclodextrin derivative of claim 1 as a pesticide synergist.
5. A pesticidal composition comprising the amino acid cyclodextrin derivative of claim 1 and a pesticide.
6. A preparation method of an inclusion compound of an amino acid cyclodextrin derivative and a pesticide is characterized by comprising the following steps:
dissolving the amino acid cyclodextrin derivative of claim 1 in water with continuous stirring until a saturated solution is formed; dissolving a pesticide in a proper amount of cosolvent, then dropwise adding the pesticide solution into the amino acid cyclodextrin derivative saturated solution to form a mixed solution, continuously stirring and reacting for 18-48 hours, cooling the mixed solution to 4 ℃, standing, after the precipitate is completely separated out, carrying out suction filtration, washing the precipitate with water and ethanol, and carrying out vacuum drying to prepare the amino acid cyclodextrin derivative and pesticide clathrate compound.
7. The preparation method according to claim 6, wherein the amount ratio of the amino acid cyclodextrin derivative to the pesticide in the mixed solution is 3: 1-3.
8. The method of claim 6, wherein the pesticide is an insecticide.
9. The preparation method according to claim 6, wherein the pesticide is indoxacarb, pyraoxystrobin and/or chlorfenapyr.
10. The process according to claim 6, wherein the stirring reaction temperature is 50 ℃.
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