CN116831126B - Spring thunder acetamide composition and application thereof - Google Patents
Spring thunder acetamide composition and application thereof Download PDFInfo
- Publication number
- CN116831126B CN116831126B CN202311103321.XA CN202311103321A CN116831126B CN 116831126 B CN116831126 B CN 116831126B CN 202311103321 A CN202311103321 A CN 202311103321A CN 116831126 B CN116831126 B CN 116831126B
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- Prior art keywords
- kasugamycin
- acetamide
- salt
- spring thunder
- mass
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- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 title claims abstract description 178
- 239000000203 mixture Substances 0.000 title claims abstract description 58
- 239000000575 pesticide Substances 0.000 claims abstract description 9
- PVTHJAPFENJVNC-MHRBZPPQSA-N kasugamycin Chemical compound N[C@H]1C[C@H](NC(=N)C(O)=O)[C@@H](C)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@H](O)[C@@H]1O PVTHJAPFENJVNC-MHRBZPPQSA-N 0.000 claims description 105
- 150000003839 salts Chemical class 0.000 claims description 39
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- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 22
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- ZDRBJJNXJOSCLR-YZKQBBCCSA-N 2-amino-2-[(2r,3s,5s,6r)-5-amino-2-methyl-6-[(2r,3s,5s,6s)-2,3,4,5,6-pentahydroxycyclohexyl]oxyoxan-3-yl]iminoacetic acid;hydron;chloride Chemical compound Cl.N[C@H]1C[C@H](N=C(N)C(O)=O)[C@@H](C)O[C@@H]1OC1[C@H](O)[C@@H](O)C(O)[C@H](O)[C@@H]1O ZDRBJJNXJOSCLR-YZKQBBCCSA-N 0.000 description 9
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- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 2
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 239000005909 Kieselgur Substances 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
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- 235000019270 ammonium chloride Nutrition 0.000 description 2
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- YDEXUEFDPVHGHE-GGMCWBHBSA-L disodium;(2r)-3-(2-hydroxy-3-methoxyphenyl)-2-[2-methoxy-4-(3-sulfonatopropyl)phenoxy]propane-1-sulfonate Chemical compound [Na+].[Na+].COC1=CC=CC(C[C@H](CS([O-])(=O)=O)OC=2C(=CC(CCCS([O-])(=O)=O)=CC=2)OC)=C1O YDEXUEFDPVHGHE-GGMCWBHBSA-L 0.000 description 2
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- NAPCRKAUXHXHCU-JLNGJXGCSA-N 2-amino-2-[(2r,3s,5s,6r)-5-amino-2-methyl-6-[(2r,3s,5s,6s)-2,3,4,5,6-pentahydroxycyclohexyl]oxyoxan-3-yl]iminoacetic acid;sulfuric acid Chemical compound OS(O)(=O)=O.N[C@H]1C[C@H](N=C(N)C(O)=O)[C@@H](C)O[C@@H]1OC1[C@H](O)[C@@H](O)C(O)[C@H](O)[C@@H]1O.N[C@H]1C[C@H](N=C(N)C(O)=O)[C@@H](C)O[C@@H]1OC1[C@H](O)[C@@H](O)C(O)[C@H](O)[C@@H]1O NAPCRKAUXHXHCU-JLNGJXGCSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 244000241257 Cucumis melo Species 0.000 description 1
- 235000015510 Cucumis melo subsp melo Nutrition 0.000 description 1
- 102000010911 Enzyme Precursors Human genes 0.000 description 1
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- 241000233866 Fungi Species 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 244000068988 Glycine max Species 0.000 description 1
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- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 238000004566 IR spectroscopy Methods 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
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- 240000003768 Solanum lycopersicum Species 0.000 description 1
- FJJCIZWZNKZHII-UHFFFAOYSA-N [4,6-bis(cyanoamino)-1,3,5-triazin-2-yl]cyanamide Chemical compound N#CNC1=NC(NC#N)=NC(NC#N)=N1 FJJCIZWZNKZHII-UHFFFAOYSA-N 0.000 description 1
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- KNWQCSNHLISUDU-UHFFFAOYSA-N acetamide;sulfuric acid Chemical compound CC(N)=O.OS(O)(=O)=O KNWQCSNHLISUDU-UHFFFAOYSA-N 0.000 description 1
- AXJDEHNQPMZKOS-UHFFFAOYSA-N acetylazanium;chloride Chemical compound [Cl-].CC([NH3+])=O AXJDEHNQPMZKOS-UHFFFAOYSA-N 0.000 description 1
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Classifications
-
- 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
- A01N43/02—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms
- A01N43/04—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom
- A01N43/14—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom six-membered rings
- A01N43/16—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom six-membered rings with oxygen as the ring hetero atom
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01P—BIOCIDAL, PEST REPELLANT, PEST ATTRACTANT OR PLANT GROWTH REGULATORY ACTIVITY OF CHEMICAL COMPOUNDS OR PREPARATIONS
- A01P1/00—Disinfectants; Antimicrobial compounds or mixtures thereof
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01P—BIOCIDAL, PEST REPELLANT, PEST ATTRACTANT OR PLANT GROWTH REGULATORY ACTIVITY OF CHEMICAL COMPOUNDS OR PREPARATIONS
- A01P3/00—Fungicides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H1/00—Processes for the preparation of sugar derivatives
- C07H1/06—Separation; Purification
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H15/00—Compounds containing hydrocarbon or substituted hydrocarbon radicals directly attached to hetero atoms of saccharide radicals
- C07H15/20—Carbocyclic rings
- C07H15/207—Cyclohexane rings not substituted by nitrogen atoms, e.g. kasugamycins
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P17/00—Preparation of heterocyclic carbon compounds with only O, N, S, Se or Te as ring hetero atoms
- C12P17/02—Oxygen as only ring hetero atoms
- C12P17/06—Oxygen as only ring hetero atoms containing a six-membered hetero ring, e.g. fluorescein
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12R—INDEXING SCHEME ASSOCIATED WITH SUBCLASSES C12C - C12Q, RELATING TO MICROORGANISMS
- C12R2001/00—Microorganisms ; Processes using microorganisms
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Abstract
The application provides a spring thunder acetamide composition and application thereof, wherein the content of spring thunder acetamide and/or spring thunder acetamide salt is not less than 0.01 percent based on the total mass of the composition. The spring thunder acetamide composition has good antibacterial effect and has application prospect as pesticide bactericides.
Description
Technical Field
The application belongs to the technical field of agriculture, and particularly relates to a spring thunder acetamide composition and application thereof.
Background
At present, no relevant report exists on the preparation process and detection method of the spring thunder acetamide (CAS 6189-95-3 or 21256-64-4 or 38420-31-4, the structure of which is shown as formula one), and the efficacy and application of the spring thunder acetamide have not been researched and developed yet.
Disclosure of Invention
Aiming at the problems in the prior art, the application provides a preparation method and a detection method of the spring thunder acetamide, and discovers that a composition containing the spring thunder acetamide and/or the salt of the spring thunder acetamide has good antibacterial effect and has application prospect as a pesticide bactericide.
In one aspect of the present application, there is provided a spring thunder acetamide composition comprising spring thunder acetamide and/or a salt of spring thunder acetamide, wherein the content of the spring thunder acetamide and/or the salt of spring thunder acetamide is not less than 0.01% by weight of the total mass of the composition, and the mass of the salt of spring thunder acetamide is calculated by the mass of the spring thunder acetamide contained in the spring thunder acetamide composition.
Optionally, the spring thunder acetamide and/or the salt of spring thunder acetamide is not less than 0.03%, or not less than 0.05%, or not less than 0.1%, or not less than 0.5%, or not less than 1% by weight of the total mass of the composition, wherein the mass of the salt of spring thunder acetamide is based on the mass of spring thunder acetamide contained therein.
From the viewpoint of cost and the like, the content of the spring thunder acetamide and/or the salt of the spring thunder acetamide is not higher than 10%, preferably not higher than 8% or not higher than 7% based on the total mass of the composition.
Optionally, the composition further comprises kasugamycin and/or a salt of kasugamycin, wherein the mass ratio of the kasugamycin and/or the salt of kasugamycin to the kasugamycin and/or the salt of kasugamycin is 10:1-200:1, wherein the mass of the salt of the kasugamycin is calculated by the mass of the kasugamycin contained in the composition.
Optionally, the mass ratio of the salt of kasugamycin and/or kasugamycin to the salt of kasugamycin and/or kasugamycin is from 13:1 to 130:1, or optionally, the mass ratio of the salt of kasugamycin and/or kasugamycin to the salt of kasugamycin is a range of values between any one or any two of 11:1, 13:1, 14:1, 15:1, 16:1, 20:1, 25:1, 30:1, 35:1, 40:1, 45:1, 50:1, 60:1, 70:1, 80:1, 91:1, 92:1, 93:1, 94:1, 95:1, 96:1, 97:1, 98:1, 99:1, 110:1, 120:1, 140:1, 150:1, 160:1, 170:1, 180:1 or 190:1, wherein the mass of the salt of kasugamycin is calculated as the mass of the salt of the kasugamycin contained therein.
Optionally, the composition is any one of a drug substance, or a formulation.
Optionally, the formulation is selected from any one of powder, granule, large granule, fine granule, microparticle, microcapsule, wettable powder, oil dispersion powder, water dispersion granule, emulsion, effervescent granule, dispersible tablet, effervescent tablet, sustained release agent, sustained release block, sustained release tube, sustained release granule, soluble powder, soluble granule, soluble tablet, soluble liquid, aqueous solution, soluble solution, oil, film spreading oil, ultra low volume liquid, ultra low volume microcapsule suspension, emulsifiable, latex, dispersible liquid, paste, concentrated gelatin, aqueous emulsion, oil emulsion, microemulsion, grease, suspension, microcapsule suspension, oil suspension, suspoemulsion, seed treatment dispersible powder, seed treatment soluble powder, seed treatment liquid, seed treatment emulsion, seed treatment suspension, seed treatment microcapsule suspension.
Optionally, the total content of the salt of kasugamycin and/or kasugamycin and the salt of kasugamycin and/or kasugamycin in the formulation is not less than 0.01%, or not less than 0.03%, or not less than 0.1%, or not less than 1%, based on the total mass of the formulation, wherein the mass of the salt of kasugamycin is based on the mass of the kasugamycin contained therein.
Another aspect of the present application is to provide the use of the composition as described above for controlling plant diseases.
Optionally, the plant disease is Curvularia lunata leaf spot and/or Pyricularia oryzae.
Another aspect of the present application is to provide the use of the composition as described above for the preparation of a plant disease control formulation.
Optionally, the plant disease is Curvularia lunata leaf spot and/or Pyricularia oryzae.
In another aspect of the present application, there is provided a method for preparing high purity spring thunder acetamide, comprising the steps of fermentation broth purification and octadecylsilane chemically bonded silica column separation.
Optionally, the broth purification step comprises the steps of:
1) Acidifying and filtering the fermentation liquor;
2) Adsorbing the filtrate with resin and then resolving;
3) The resolved solution was filtered off by nanofiltration.
Optionally, the nanofiltration impurity further comprises a decoloring treatment procedure.
Further, the acidulant in the fermentation broth purification step 1 includes at least one of sulfuric acid, hydrochloric acid, phosphoric acid or oxalic acid.
Further, the resin in the fermentation broth purification step 2 is a strongly acidic cation exchange resin.
Further, the resin adsorption desorbent in the fermentation broth purification step 2 comprises at least one of an ammonium chloride solution, a sodium hydroxide solution or a sodium chloride solution.
Optionally, in the silica gel column separation step, the eluting phase is acetonitrile and alkyl sodium sulfonate mixed solution;
further, the sodium alkyl sulfonate is optionally sodium hexane sulfonate or sodium dodecyl sulfonate, and acetonitrile: sodium alkyl sulfonate solution=1%: 99% -10%:90%.
The applicant has unexpectedly found that the spring thunder acetamide has very sensitive response at the ultraviolet detection wavelength of 195 nm of liquid chromatography, and therefore another aspect of the present application is to provide a method for detecting spring thunder acetamide, comprising the steps of:
dissolving a sample to be tested in deionized water to prepare a solution with the concentration of 0.001-4 mg/mL, taking a proper amount of the solution to be tested, injecting the solution into liquid chromatography, judging whether the solution contains the kasugamycin acetamide according to the peak position or comparing the peak position with the peak position of a kasugamycin acetamide standard product, and determining whether the solution contains the kasugamycin acetamide, wherein the detection wavelength is 195 nm.
Optionally, the HPLC column is a reverse phase C18 packing;
optionally, a mobile phase acetonitrile and an aqueous sodium alkyl sulfonate solution;
optionally, the operation time is 10-20 min;
optionally, the column temperature is 30+/-2 ℃;
optionally, the flow rate is 0.5-2 mL/min;
optionally, the signal bandwidth is 4 nm-8 nm;
optionally, the sample is introduced in an amount of 5. Mu.L.
Further, the sodium alkyl sulfonate is optionally sodium hexane sulfonate or sodium dodecyl sulfonate, and acetonitrile: sodium alkyl sulfonate solution=1%: 99% -10%:90%.
As can be determined by those skilled in the art, under the condition of the standard substance, the liquid phase data (map) of the sample to be detected and the liquid phase data (map) of the standard substance are compared under the same liquid phase analysis condition to determine whether the sample to be detected contains the spring thunder acetamide, and the content (concentration) of the spring thunder acetamide in the sample to be detected can be further determined through the content (concentration) of the standard substance.
The application has the positive progress effects that:
the application provides a composition of spring thunder acetamide and/or spring thunder acetamide salt, which has obvious inhibition effect on plant pathogenic bacteria; furthermore, the salt of the kasugamycin and/or the kasugamycin shows beneficial synergistic effect under the control of a certain proportion, and can be better applied to the prevention and treatment of plant diseases.
The application also provides a preparation method of the high-purity spring thunder acetamide, and the obtained high-purity spring thunder acetamide can be used as a standard substance or applied to the aspects of active ingredient detection and the like.
Drawings
FIG. 1 is a graph showing the purity of the prepared spring thunder acetamide in example 1;
FIG. 2 is a liquid mass spectrum ultraviolet chromatograph (HPLC-DAD) and total ion flow chart (TIC) of the spring thunder acetamide prepared in example 1;
FIG. 3 is a liquid phase mass spectrum (HPLC-MSD) of the spring thunder acetamide prepared in example 1;
FIG. 4 is a hydrogen nuclear magnetic spectrum (1H-NMR) of the spring thunder acetamide prepared in example 1;
FIG. 5 is an infrared spectrum (FTIR) of the spring radar acetamide prepared in example 1;
FIG. 6 is a liquid chromatography (HPLC) of a kasugamycin aqueous composition;
FIG. 7 shows the bacteriostatic effect of various concentrations of kasugamycin against Pyricularia oryzae, wherein ck is a blank, a is 0.001wt% of the bacteriostatic effect, b is 0.01wt% of the bacteriostatic effect, c is 0.03 wt% of the bacteriostatic effect, d is 0.05wt% of the bacteriostatic effect, and e is 0.1wt% of the bacteriostatic effect.
For the purposes of the present application, unless otherwise indicated, the terms used herein have the following meanings:
the term "crude drug" refers to a product obtained during the production process and composed of an active ingredient and related impurities, and small amounts of additives may be added if necessary. For example, a kasugamycin raw drug refers to a product consisting of kasugamycin and/or a salt of kasugamycin and related impurities obtained during the production process, and if necessary, a small amount of additives may be added.
The term "parent drug" refers to a product obtained during the production process, consisting of the active principle and related impurities, possibly with small amounts of necessary additives and suitable diluents. For example, a kasugamycin mother drug refers to a product consisting of kasugamycin and/or a salt of kasugamycin and related impurities obtained during the manufacturing process, possibly with small amounts of necessary additives and suitable diluents.
The term "formulation" refers to a stable product processed from a pesticide base or parent and suitable adjuvants, or processed by methods such as biological fermentation, plant extraction, and the like.
The term "adjuvant" refers to any substance, other than the active ingredient, which is added to a pesticidal product, does not itself have pesticidal activity and active ingredient function, but is capable of or contributes to the enhancement, improvement, or physical and chemical properties of the pesticidal product, of a single component or of multiple components.
The terms "about", "about" and "substantially" refer to a numerical variation in the content of the error range of a normal experiment or measurement, e.g., that "substantially" represents an error of no more than 15%, preferably no more than 10%.
The term "plant disease" refers to a phenomenon that a plant is significantly hindered from growing and developing due to infection by other organisms and adverse abiotic factors during the growth and development of the plant, and pathological changes and even death occur in physiological and tissue structures inside and outside the plant, resulting in reduced yield and deteriorated quality. "plant disease" according to the present application refers in particular to diseases of plants caused by infestation by other organisms including, but not limited to, fungi (e.g., curvularia zeae, pyricularia oryzae), or bacteria (e.g., melon bacterial angular leaf spot), and the like.
The term "salt of kasugamycin" refers to a compound formed by combining kasugamycin with an acid ion, such as kasugamycin hydrochloride, kasugamycin sulfate, kasugamycin carboxylate, kasugamycin phosphate, kasugamycin nitrate, or kasugamycin carbonate.
The term "salt of spring thunder acetamide" refers to a compound formed by combining spring thunder acetamide with acid radical ions, such as spring thunder acetamide hydrochloride, spring thunder acetamide sulfate and the like.
In the present application, the mass of the salt of kasugamycin is calculated on the mass of the kasugamycin contained therein, and the mass of the salt of kasugamycin is calculated on the mass of the kasugamycin contained therein. For example, if the composition contains 41.6g of kasugamycin hydrochloride and 1g of kasugamycin acetamide, the mass ratio of the kasugamycin hydrochloride to the kasugamycin acetamide is 37.9:1 (calculated as: the molecular weight of the kasugamycin hydrochloride is 416, and the molecular weight of the kasugamycin is 379, so that the 41.6g of the kasugamycin hydrochloride contains 37.9 of the kasugamycin, and the mass ratio of the kasugamycin hydrochloride to the kasugamycin acetamide is 37.9:1).
Detailed Description
The reagents and solvents used in the following examples are either commercially available or prepared by conventional methods known to those skilled in the art. All commercial reagents and solvents were not further purified.
1. Preparation example
Example 1: preparation of spring thunder acetamide
1) High-yield streptomyces aureofaciens is selectedStreptomycesmicroaureaus) The strain MKL-2 is used as zymogen, seed liquid after being cultured by a seed culture medium is inoculated into a 50L fermentation tank for fermentation, wherein the culture medium in the fermentation tank comprises 4.0% of soybean cake powder, 0.07% of potassium dihydrogen phosphate, 0.3% of sodium chloride, 0.72% of soybean oil, 1.1% of corn steep liquor dry powder, 0.01% of polyoxypropylene polyoxyethylene glyceryl ether GPE, 0.4% of ammonia water and 0.1% of sodium citrate; the fermentation temperature is 30 ℃, the rotating speed is 60 rpm, ammonia water is dripped in during the fermentation process, the pH value of a fermentation system is controlled to be 7.1+/-0.1, so that the production of the spring thunder acetamide is facilitated, and 120 h is cultivated;
2) Taking 20L spring thunder acetamide fermentation liquor, adopting oxalic acid to acidify the fermentation liquor, and then adopting ceramic membranes to filter;
3) Collecting filtrate, adsorbing with strong acid cation exchange resin, and resolving with ammonium chloride solution;
4) Filtering the analysis liquid with a nanofiltration membrane, concentrating in vacuum, and collecting concentrated filtrate;
5) Decolorizing the concentrated filtrate by using active carbon;
6) Adding the decolorized filtrate into octadecylsilane chemically bonded silica column, and separating and purifying with mixed solution of 10% acetonitrile and 90% sodium hexane sulfonate aqueous solution as eluent;
7) The separated and purified solution was dried to obtain about 6g spring acetamide powder.
The spring thunder acetamide powder can be directly used as a raw medicine or a mother medicine of pesticide.
Example 2: preparation of kasugamycin acetamide aqua
Taking 100 mg of the technical scheme of the spring thunder acetamide in the example 1, adding the technical scheme into 10 mL of deionized water to prepare a spring thunder acetamide water aqua with the content of 1%, and taking a proper amount of the 1% water aqua to further dilute and prepare 4 spring thunder acetamide water aquas with different contents with the mass fractions of 0.01%, 0.1%, 0.3% and 0.5%.
Example 3: preparation of spring thunder acetamide wettable powder
The following components are provided:
spring thunder acetamide technical 1g prepared in example 1;
sodium dodecyl sulfate (wetting agent) 4 g;
sodium lignin sulfonate (dispersant) 5 g;
white carbon black (filler) 10 g;
diatomaceous earth (filler) 80 g;
the components are fully mixed according to the weight of the formula, and the mixture is crushed by a superfine crusher to obtain 1 percent of the kasugamycin acetamide wettable powder.
Example 4: preparation of kasugamycin acetate and kasugamycin aqua
Taking a kasugamycin hydrochloride technical 85 mg (supplied by Sesamidedi bioengineering Co., ltd.) and a kasugamycin acetamide technical 1.5 mg prepared in example 1, dissolving the technical in 50 ml deionized water to prepare a kasugamycin/kasugamycin aqua.
Example 5: preparation of kasugamycin and kasugamycin wettable powder
The following components are provided:
spring thunder acetamide technical 1g prepared in example 1;
kasugamycin hydrochloride prodrug 13 g (available from sienmeisi bioengineering limited);
sodium dodecyl sulfate (wetting agent) 3 g;
sodium lignin sulfonate (dispersant) 5 g;
white carbon black (filler) 10 g;
diatomaceous earth (filler) 68 g;
the components are fully mixed according to the weight of the formula, and the powder is crushed by a superfine crusher to obtain the kasugamycin wettable powder.
2. Authentication and characterization
1. Purity determination
1.1 preparation of a solution to be tested: accurately weighing 38 mg of the spring radar acetamide prepared in the example 1, dissolving the spring radar acetamide in water and diluting the solution to 25 mL to prepare a spring radar acetamide standard stock solution; accurately transferring the standard stock solution of 1.25 and mL into a 25 mL measuring flask, diluting with water to the scale mark, and uniformly mixing to obtain the solution to be measured.
1.2 analysis conditions were as follows:
instrument Agilent HPLC 1100;
HPLC chromatographic column Agilent aichrombond-AQ C18.6 mm250mm/>5μm；
Mobile phase acetonitrile 20MM sodium hexane sulfonate aqueous solution (H) 3 PO 4 Adjusting pH to 3) =5%: 95% (v/v);
the running time is 13 min;
column temperature is 30 ℃;
sample injection amount is 5 mu L;
a detection wavelength of 195 nm;
the flow rate is 1.0 mL/min;
signal bandwidth 4 nm.
As a result, as shown in FIG. 1, the retention time of the spring thunder acetamide is 10.469 min, and the purity factor is 999.843, which indicates that the method of example 1 of the present application can prepare spring thunder acetamide with high purity. The high-purity spring thunder acetamide can be used as a standard substance.
2. Liquid phase Mass Spectrometry (HPLC-MSD)
Accurately weighing the standard product prepared in the example 1 of 25.06 mg into a 25 mL volumetric flask, dissolving with water, fixing the volume, and uniformly mixing to obtain a standard stock solution.
Accurately transferring the standard stock solution of 0.50 and mL into a volumetric flask of 10 mL, and then using water to fix the volume to the scale mark and uniformly mixing. The analysis conditions were as follows:
liquid phase conditions:
instrument Agilent 1100/1200 HPLC;
HPLC chromatographic column Waters CORTECS HILIC, 150 x 4.6mm, 2.7 μm;
mobile phase acetonitrile: 50 mmol ammonium formate solution = 75:25 (V/V);
column temperature is 30 ℃;
sample injection volume is 5 mu L;
the running time is 12.00 min;
the flow rate is 1.00 mL/min;
a detection wavelength of 205 nm;
signal bandwidth 4 nm;
off the reference wavelength;
off the reference bandwidth;
spectral range All (190 nm-400 nm).
MS conditions:
MS source, API-ES;
the polarity is positive;
70V collision voltage;
the temperature of the drying gas is 350 ℃;
the flow rate of the drying gas is 12.0L/min;
cap voltage 3000V;
the acquisition mode is Scan;
scanning range is 100-1000 amu.
Results:
ultraviolet chromatography (DAD) and total ion flow diagram (TIC) are shown in fig. 2, wherein DAD retention time is about 6.8min, and TIC retention time is about 7.0 min; the mass spectrum is shown in figure 3, and the m/z of the main fragment ions are 171, 351, 373 and 701, which are consistent with the structural characteristics of the spring thunder acetamide.
3. Nuclear magnetic analysis (1H-NMR)
The analysis method is as follows:
a7 mg solid sample was dissolved in a heavy aqueous solvent and subjected to nuclear magnetic analysis on Bruker AVANCE NEO (with BBO probe, bruker, GER).
The nuclear magnetic data are shown in fig. 4, and the related characteristics accord with chemical structural characteristics of the spring thunder acetamide.
4. Infrared test (FTIR)
About 2 g of spectrally pure KBr was weighed, ground and dried at 105℃for 2h, after which KBr was transferred to a dryer and cooled to room temperature. The analysis standard for spring thunder acetamide of 10 mg was weighed, dried at 105 ℃ for 2h, and then transferred to a dryer for cooling to room temperature.
About 200 mg anhydrous KBr powder was weighed into an agate mortar, ground and tableted by an infrared spectroscopy tableting device. The potassium bromide salt tablets were scanned with an infrared spectrometer.
About 2 mg dry spring thunder acetamide analytical standard is weighed into KBr of about 200 mg, mixed evenly and ground. The mixture is pressed into semitransparent sheets by an infrared spectrum pressing device and then scanned by an infrared spectrometer.
The FTIR results are shown in fig. 5, where the relevant infrared characteristic peaks correspond to the absorption peak positions of the corresponding groups in the chemical structure of the spring thunder acetamide.
5. Detection of kasugamycin acetate-kasugamycin aqueous composition
The kasugamycin aqueous solution of example 4 was analyzed by HPLC under the following conditions:
instrument Agilent HPLC 1100;
HPLC chromatographic column Agilent aichrombond-AQ C18.6 mm250mm/>5μm；
Mobile phase acetonitrile 20MM sodium hexane sulfonate aqueous solution (H) 3 PO 4 Adjusting pH to 3) =5%: 95% (v/v);
the running time is 13 min;
column temperature is 30 ℃;
a detection wavelength of 195 nm;
the flow rate is 1.0 mL/min;
signal bandwidth 4 nm;
the sample injection amount is 5 mu L.
As shown in FIG. 6, the retention time of kasugamycin and kasugamycin acetamide is 8.462 min and 10.464 min respectively, which shows that the detection method of the application has good response of separation degree and sensitivity to the kasugamycin and the kasugamycin acetamide with similar structures, and the detection method of the application can effectively identify the kasugamycin and the kasugamycin acetamide with similar structures.
Without being limited to the examples of embodiment of the present application, it is also within the scope of the present application to perform routine operations based on the specific embodiments of the present application, such as separation and adjustment of detection parameters according to the analysis apparatus.
3. Effect experiment
Example 6: spring thunder acetamide antibacterial test
Raw materials the preparation of the technical product of the spring thunder acetamide is carried out according to the method of the example 1.
Pathogenic bacteria, namely, corn curvularia is obtained by collecting corn disease leaves from a Weinan city farm, separating and purifying by a tissue separation method, and identifying; the rice blast is obtained by separating, purifying and cultivating field disease rice.
The preparation method comprises the steps of taking the kasugamycin aqueous solution 1mL with the mass fractions of 0.01%, 0.1%, 0.3%, 0.5% and 1% in the example 2 in sequence, uniformly mixing the kasugamycin aqueous solution 1mL with the PSA culture medium according to the proportion of 1mL to 9mL, pouring the mixture into a culture dish, and preparing drug-containing flat plates with the final concentrations of 0.001%, 0.01%, 0.03%, 0.05% and 0.1% respectively, so as to prepare a blank control by adding the PSA culture medium with the same amount of sterile water.
Preparing a bacterial cake with the diameter of 5 mm by using a puncher for the cultured pathogen to be tested, placing the bacterial cake into the flat plate, culturing the bacterial cake in an incubator with the temperature of 28+/-1 ℃, measuring the bacterial colony diameter of each treatment group by adopting a crisscross method when the bacterial colony edge of a control group is close to the wall of a culture dish, and calculating the relative inhibition percentage, wherein the calculation formula is as follows:
inhibition (%) = (control colony diameter-treated colony diameter)/(control colony diameter-cake diameter) ×100%;
the inhibition rate is judged to be effective (delta) between 1 and 24 percent, 25 to 39 percent is judged to be effective (delta), and more than or equal to 40 percent is judged to be effective (delta).
The inhibition rate measurement results and the antibacterial test results are shown in table 1 and fig. 7.
TABLE 1 inhibition of two pathogens by spring thunder acetamide
As can be seen from Table 1 and FIG. 7, the inhibition effect of kasugamycin on rice blast bacteria is similar to that of kasugamycin, and the kasugamycin has higher sensitivity, the effective effect is shown at the concentration of 0.01%, the remarkable effect is shown at the concentration of 0.03%, and the inhibition rate reaches 41.6%. Meanwhile, the kasugamycin has obvious inhibition effect on the corn curvularia bacteria insensitive to the kasugamycin, the kasugamycin is effective on the corn curvularia bacteria at the concentration of 0.01 percent, and the inhibition rate reaches 42.2 percent at the concentration of 0.05 percent. The above experimental results show that the effects of kasugamycin and kasugamycin on the control of certain pathogenic bacteria are similar, which may be related to their chemical structural similarity. However, for some pathogens, there is a large difference in their control effect, which may be indicative of a large difference in the mechanism of action and/or the effect of action.
Example 7: indoor toxicity test of kasugamycin and kasugamycin composition on rice blast
1. Inhibition Medium concentration assay (EC 50)
Raw material of spring thunder acetamide raw material (prepared by the method of example 1); kasugamycin crude drug (kasugamycin hydrochloride, supplied by sienmeisi bioengineering limited); the rice blast is obtained by separating, purifying and cultivating field disease rice.
The test method refers to a potting method of ' national agricultural industry standard NY/Tll54.7-2006 of the people's republic of China '. Selecting three-leaf rice seedlings with consistent growth vigor, wherein 2 seedlings are planted in each potEach treatment uses 5 pots of test rice seedlings. Culturing Pyricularia oryzae on tomato oat agar medium, and washing spores with sterile water to obtain 1×10 5 The suspension of each spore/mL is evenly sprayed and inoculated on the rice seedlings to be tested, and a black plastic bag is sleeved for moisture preservation and culture for 24 hours after inoculation. 24h after inoculation, treatment with the agents was performed, each agent being set at 5 concentration gradients, sprayed with a Potter spray tower at a pressure of 50Psi, approximately 5mL per pot. After spraying, the seedlings are cultivated at 28 ℃ and 92% relative humidity, and after 8 days, disease indexes of the whole plant of leaves are investigated according to disease grading standards of rice blast, and control effects are calculated.
Disease index = { [ Σ (number of leaf of each stage of disease of each treatment×number of corresponding stage) ]/total leaf number of investigation×9} ×100;
control effect (%) = [ (blank control disease index-agent treatment disease index)/blank control disease index ] ×100.
The control effect is converted into a few-rate value (y), the concentration (ug/ml) of the liquid medicine is converted into a pair value (x), and the toxicity equation and the concentration EC50 in inhibition are calculated by a least square method.
2. Experiment of common toxicity of kasugamycin and kasugamycin composition
According to the grand cloud Peel method, the toxicity index and co-toxicity coefficient (CTC) of the kasugamycin-kasugamycin composition are calculated.
Single dose toxicity index= (standard dose EC 50/test single dose EC 50) x 100;
measured virulence index (ATI) = (standard agent EC 50/test agent EC 50) ×100;
the theoretical drug toxicity index (TTI) =a drug toxicity index x percentage of drug in the drug mixture+b drug toxicity index x percentage of drug in the drug mixture;
co-toxicity coefficient (CTC) = [ mix measured toxicity index (ATI)/mix Theoretical Toxicity Index (TTI) ]x100;
when CTC is less than or equal to 80, the composition shows antagonism, when CTC is less than or equal to 80 and CTC is less than or equal to 120, the composition shows additive effect, and when CTC is more than or equal to 120, the composition shows synergistic effect.
The determination results of the co-toxicity test are shown in Table 2.
TABLE 2 Co-toxicity test data
According to the experiment of the co-toxicity of the kasugamycin and kasugamycin composition, the kasugamycin and the kasugamycin show synergistic effect within the mass ratio of 13:1-130:1, and the kasugamycin have good synergistic effect after being mixed according to a certain proportion, so that the control effect on rice blast can be improved.
The experimental results show that although the chemical structures of the kasugamycin and the kasugamycin are similar, the kasugamycin and the kasugamycin have obvious difference in the prevention and treatment effect of pathogenic bacteria, and have certain complementarity and cooperativity. Although the intrinsic mechanism is not yet understood, it is speculated that this is a result of the enhanced permeability of substances on the pathogenic cell wall, probably due to the better lipophilicity of kasugamycin compared to kasugamycin.
The above examples are preferred embodiments of the present application, but the embodiments of the present application are not limited to the above examples, and any other changes, modifications, substitutions, combinations, and simplifications that do not depart from the spirit and principle of the present application should be made in the equivalent manner, and the embodiments are included in the protection scope of the present application.
Finally, it is also noted that the terms "comprises," "comprising," or any other variation thereof, are intended to cover a non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements does not include only those elements but may include other elements not expressly listed or inherent to such process, method, article, or apparatus.
Claims (8)
1. A spring thunder acetamide pesticide composition, which is characterized in that the spring thunder acetamide pesticide composition contains spring thunder acetamide and/or salt of spring thunder acetamide; the content of the spring thunder acetamide and/or the salt of the spring thunder acetamide is 0.01% -10% based on the total mass of the pesticide composition;
wherein the mass of the salt of the spring thunder acetamide is calculated by the mass of the spring thunder acetamide contained in the salt;
the spring thunder acetamide is a compound shown in a formula I,
formula I;
the pesticide composition also comprises kasugamycin and/or a salt of the kasugamycin, wherein the mass ratio of the kasugamycin and/or the salt of the kasugamycin to the kasugamycin and/or the salt of the kasugamycin is 10:1-200:1;
wherein the mass of the salt of kasugamycin is calculated by the mass of the kasugamycin contained in the salt.
2. A pesticidal composition according to claim 1, wherein the content of the spring thunder acetamide and/or the salt of spring thunder acetamide is 0.03-10% by weight of the total mass of the pesticidal composition.
3. Pesticide composition according to claim 1 or 2, characterized in that the mass ratio of kasugamycin and/or a salt of kasugamycin to kasugamycin and/or a salt of kasugamycin is 13:1-130:1.
4. The pesticidal composition of claim 1 or 2, wherein said pesticidal composition is any one of a bulk, a parent or a formulation.
5. The pesticidal composition of claim 4, wherein the formulation is in a dosage form selected from any of granules, macrogranules, fine granules, microgranules, microcapsule, wettable powder, oil dispersion powder, water dispersible granule, emulsion, effervescent granule, dispersible tablet, effervescent tablet, slow release agent, slow release block, slow release tube, slow release granule, soluble powder, soluble granule, soluble tablet, soluble liquid, soluble solution, film spreading oil, ultra low volume liquid, ultra low volume microcapsule suspension, emulsifiable concentrate, latex, dispersible liquid, paste, strong gum, aqueous emulsion, oil emulsion, microemulsion, grease, microcapsule suspension, oil suspension, suspoemulsion, seed treatment dispersible powder, seed treatment soluble powder, seed treatment liquid, seed treatment emulsion, seed treatment suspension, seed treatment microcapsule suspension.
6. The pesticidal composition of claim 4, wherein said formulation is in a form selected from any of a powder, a liquid, an oil or a suspension.
7. Use of the pesticidal composition according to any one of claims 1 to 6 for controlling plant diseases, wherein the plant diseases are curvularia lunata leaf spot and/or rice blast.
8. Use of the pesticidal composition according to any one of claims 1 to 6 for the preparation of a plant disease control formulation, wherein the plant disease is curvularia lunata leaf spot and/or rice blast.
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| CN105284822B (en) * | 2015-11-19 | 2017-06-30 | 南京农业大学 | A kind of composition pesticide containing Tebuconazole for preventing and treating gibberella zeaze petch of wheat and barley and application thereof |
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- 2023-08-30 CN CN202311714813.2A patent/CN117694347A/en active Pending
- 2023-08-30 CN CN202311103321.XA patent/CN116831126B/en active Active
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| CN116831126A (en) | 2023-10-03 |
| CN117694347A (en) | 2024-03-15 |
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Effective date of registration: 20231208 Address after: 715500 Pucheng high tech Industrial Development Zone, Weinan, Shaanxi Patentee after: SHAANXI MICROBE BIOTECHNOLOGY Co.,Ltd. Patentee after: Yuanda Industry Holding Co.,Ltd. Address before: Floor 25, Building B, Yuanda Center, No. 5, Huizhong Road, Chaoyang District, Beijing 100,101 Patentee before: CHINA GRAND ENTERPRISE, Inc. Patentee before: SHAANXI MICROBE BIOTECHNOLOGY Co.,Ltd. |