CN108864230B - Organophosphorus group substituted avermectin derivative and preparation method and application thereof - Google Patents
Organophosphorus group substituted avermectin derivative and preparation method and application thereof Download PDFInfo
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H17/00—Compounds containing heterocyclic radicals directly attached to hetero atoms of saccharide radicals
- C07H17/04—Heterocyclic radicals containing only oxygen as ring hetero atoms
- C07H17/08—Hetero rings containing eight or more ring members, e.g. erythromycins
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- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N57/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic phosphorus compounds
- A01N57/18—Biocides, pest repellants or attractants, or plant growth regulators containing organic phosphorus compounds having phosphorus-to-carbon bonds
- A01N57/24—Biocides, pest repellants or attractants, or plant growth regulators containing organic phosphorus compounds having phosphorus-to-carbon bonds containing heterocyclic radicals
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H1/00—Processes for the preparation of sugar derivatives
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Abstract
The invention discloses an organophosphorus group substituted avermectin derivative, a preparation method and application thereof, wherein the general structural formula is shown as (I), and the definition of each substituent group in the formula is shown in the specification. The invention synthesizes a series of avermectin derivatives substituted by organic phosphorus groups by taking avermectin as a matrix, thereby enlarging the application range of the avermectin, and simultaneously the avermectin derivatives can be used for preventing and controlling various plant pests, are particularly suitable for lepidoptera pests, mite pests and aphids, and have strong insecticidal effect on target pests such as rice stem borer, red spider, rice planthopper and the like; the activity of the avermectin derivative substituted by the organic phosphorus group disclosed by the invention on target pests such as rice stem borer, citrus red spider, rice planthopper and the like is obviously better than that of avermectin B1a/B1bIs also obviously superior to abamectin B2a/B2bThe insecticidal spectrum is increased, and the activity is improved.
Description
Technical Field
The invention relates to the technical field of agricultural chemicals and preparation thereof, in particular to an organophosphorus group substituted avermectin derivative and a preparation method and application thereof.
Background
Avermectin (AVM for short) is a low-toxicity, high-efficiency, high-selectivity, green, environment-friendly and biogenic pesticide, and completely solves the problems of high toxicity, resistance and influence on the environment of the traditional pesticide.
The abamectin pesticide sold in the market at present is B1aIs the main insecticidal component (Avermectin B)1a+B1bIn which B is1aNot less than 90%, B1bNot more than 5%) by B1aIs calibrated. Around abamectin B1The research on the derivatives of (A) has been greatly advanced, and nearly one thousand avermectin derivatives have been synthesized and commercialized as emamectin benzoate, ivermectin, eprinomectin, emamectin, delamectin, milbemycin and the like. Abamectin B2As another important component, the compound has strong contact killing activity to nematodes and is an agricultural pesticide for killing the nematodes. But due to the defects of insufficient stability, low activity and the like, the abamectin B2As a large component of avermectin, it is largely unused and is referred to avermectin B in the prior literature and patents2The research on the synthesis and application of the derivatives is rarely reported, and the B is related to the expansion of the yield of the abamectin2The exploration and application of components is becoming increasingly important.
Today, much progress has been made around the research of avermectin derivatives, such as: the American Merck company carries out Wilkinson catalysis on a double bond between C22 and C23 of AVM B1, and obtains ivermectin after hydrogenation treatment in a homogeneous system; 4 "-methylamino-4" -deoxyabamectin benzoate was obtained by introducing a methylamino group at position 4 "of AVM B1; connecting cyclohexane to C25 position of avermectin by mutation biological synthesis method to obtain doramectin; chinese patent application 201310063563.0 discloses avermectin B2a/B2bAmino derivatives and 4' -position alkylated or acylated amino substituted avermectins B2a/2bDerivatives of ivermectin B2The utilization range of (a), which does not pay attention to the insecticidal effect of avermectin; the Chinese patent application 201410721599.8 discloses a virus insecticidal suspending agent containing abamectin, wherein the abamectin and virus are compounded according to the proportion of the invention, so that the insecticidal speed is increased to a certain extent, the insecticidal effect is faster, and the suspension only aims at various conventional agricultural and forestry pests such as diamondback moth, pine moth and cabbage caterpillar, but does not give attention to the insecticidal effect on target pests such as rice stem borer, citrus red spider and rice planthopper.
Meanwhile, with the popularization and the promotion of the abamectin and downstream products thereof in recent years, the drug resistance of the abamectin is more and more obvious, and in addition, the abamectin has very serious thermal degradation and photodegradation and short duration, and has smaller and smaller advantages compared with chemical pesticides.
In view of the above problems, those skilled in the art have endeavored to disclose avermectin derivatives having strong insecticidal effect, high activity and long lasting period of insecticidal effect and a preparation method thereof, and the present invention is thereby developed in order to achieve the effect of having a wide insecticidal range.
Disclosure of Invention
The invention aims to provide an avermectin derivative with strong insecticidal effect, high activity and long lasting insecticidal effect and a preparation method thereof, and the invention also aims to synthesize a series of avermectin derivatives substituted by organic phosphorus groups by taking avermectin as a parent so as to enlarge the utilization range of the avermectin and achieve the purpose that the avermectin derivative has strong insecticidal effect on target pests such as rice stem borer, citrus red spider, rice planthopper and the like.
In order to achieve the purpose, the invention provides the following technical scheme:
an organophosphorus group substituted avermectin derivative, which is characterized in that: the avermectin derivative has a chemical structural general formula shown in a formula (I);
wherein:
R1is methyl or ethyl; X-Y is CH ═ CH, CH2-CH(OH)；
R2Is an oxygen atom or a sulfur atom;
R3and R4May be the same or different and is C1-C8Alkyl, halo C1-C8Alkyl radical, C3-C6Cycloalkyl of, C1-C8Alkoxy, halo C1-C8Alkoxy radical, C1-C8Alkylthio, halo C1-C8Alkylthio group、C2-C8Alkenyl, halo C2-C8Alkenyl radical, C2-C8Alkynyl, halo C2-C8Alkynyl, C3-C8Alkenyloxy, halogeno C3-C8Alkenyloxy radical, C3-C8Alkynyloxy, halo C3-C8Alkynyloxy, C1-C8Alkylcarbonyloxy, C1-C8Alkylcarbonylamino, C1-C8Alkylsulfonyloxy, C1-C8Alkoxycarbonylamino, OC (═ O) N R6R7Aryl or heteroaryl unsubstituted or further substituted with 1 to 5 groups independently selected from: halogen, nitro, cyano, C1-C8Alkyl, halo C1-C8Alkyl radical, C3-C6Cycloalkyl of, C1-C8Alkoxy, halo C1-C8Alkoxy radical, C1-C8Alkylthio, halo C1-C8Alkylthio radical, C2-C8Alkenyl, halo C2-C8Alkenyl radical, C2-C8Alkynyl, halo C2-C8Alkynyl, C3-C8Alkenyloxy, halogeno C3-C8Alkenyloxy radical, C3-C8Alkynyloxy, halo C3-C8Alkynyloxy, C1-C8Alkylcarbonyloxy, C1-C8Alkylcarbonylamino, C1-C8Alkylsulfonyloxy, C1-C8Alkoxycarbonyl group, C1-C8Alkoxycarbonylamino, OC (═ O) N R6R7；
R5Is hydrogen, hydroxy, -NR6R7；
R6、R7Can be selected from hydrogen, hydroxy, C, identically or differently1-C8Alkyl radical, C1-C8Alkoxy, halo C1-C6Alkyl or C3-C6A cycloalkyl group;
R8is a hydroxyl protecting group.
The avermectin derivative substituted by the organophosphorus group can be used for preventing and controlling various plant pests, and is particularly suitable for target rice stem borers, citrus red spiders and rice planthoppers; the prevention and control effect of the organophosphorus group substituted avermectin derivative on pests is better than that of avermectin B1a/B1bAnd abamectin B2a/B2b。
The preparation method of the organophosphorus group substituted avermectin derivative is characterized by comprising the following steps: the method comprises the following four reaction modes:
(1) reacting a starting material compound (II) with an organic phosphorus-containing reagent in an inert solvent at the temperature of 60-100 ℃ in the presence of a basic catalyst to obtain a compound shown as a formula (III);
(2) reacting an initial raw material compound (II), an amination reagent and an organophosphorus-containing reagent in an inert solvent at the temperature of 80-100 ℃ in the presence of an amination catalyst to obtain a compound shown in a formula (IV);
(3) reacting a starting raw material compound (II) with an organophosphorus-containing reagent in an inert solvent at the temperature of 100-120 ℃ in the presence of an amination reagent, an amination catalyst and a basic catalyst to obtain a compound shown as a formula (V);
(4) reacting the compounds shown in the formulas (III), (IV) and (V) with a deprotection catalyst in an inert solvent at the temperature of-20-5 ℃ to obtain the compound shown in the formula (I).
The inert solvent is one or more selected from dichloromethane, dichloroethane, 1, 2-dichloroethane, sec-butyl acetate, methanol and ethanol, and the dosage of the inert solvent is 1.0-5.3 times of the weight of the compound (II).
The amination reagent is selected from one or more of triethanolamine, heptamethyldisilazane, hexamethyldisilazane, methyl amine methanol solution, tetraethylenepentamine and ethylenediamine, and the dosage of the amination reagent is 1.0-2 times of the molar weight of the compound (II).
The organophosphorus-containing reagent is any one of diethyl phosphite, diisopropyl phosphite, dibenzyl phosphite, diphenyl phosphite and dibutyl phosphite, and the dosage of the organophosphorus-containing reagent is 1.0-2 times of the molar quantity of the compound (II).
The alkaline catalyst is one or more selected from triethylamine, tributylamine, ethyldiisopropylamine and tetramethylethylenediamine, and the dosage of the alkaline catalyst is 0.5-1.0 times of the molar weight of the compound (II).
The amination catalyst is selected from one or more of zinc trifluoroacetate, zinc acetate, zinc chloride, trichloroethyl aluminum, triethyl aluminum, tetrabutyl titanate and tetraethyl titanate, and the dosage of the amination catalyst is 0.5-5% of the molar amount of the compound (II).
The deprotection catalyst is one or more of palladium acetate, palladium chloride and triphenylphosphine palladium chloride, and the dosage of the deprotection catalyst is 0.01-0.1% of the molar amount of the compound (II).
The invention has the beneficial effects that: the avermectin derivative provided by the invention has the technical effects of strong insecticidal effect, high activity and long duration of insecticidal effect, and the invention also provides a preparation method of the avermectin derivative, wherein avermectin is used as a matrix to synthesize a series of avermectin derivatives substituted by organic phosphorus groups, so that the application range of the avermectin is expanded, and meanwhile, the avermectin derivative can be used for preventing and treating various plant pests, is particularly suitable for lepidoptera pests, mite pests and aphids and has strong insecticidal effect on target rice stem borers, target mite pests, rice planthoppers and other pests; the activity of the avermectin derivative substituted by the organic phosphorus group disclosed by the invention on target pests such as rice stem borer, citrus red spider, rice planthopper and the like is obviously better than that of avermectin B1a/B1bIs also obviously superior to abamectin B2a/B2bThe insecticidal spectrum is increased, and the activity is improved.
Detailed description of the preferred embodiments
The following description is of the preferred embodiments of the present invention, and the preferred embodiments described herein are intended to be illustrative of the present invention and not limiting.
EXAMPLE 1 Compound 1, 4' -diethoxymethymethylaminefactam B1a/B1bPreparation of
5g of 5-allyloxycarbonyl-4' -carbonyl abamectin B1a/B1b(content of>90%) of the compound, dissolving the mixture in 20g of sec-butyl acetate, sequentially adding 4.9g of heptamethyldisilazane, 2.8g of diethyl phosphite and 1.1g of zinc trifluoroacetate, keeping the temperature at 50 ℃ while stirring, reacting for 2h, then cooling to-10 ℃, adding 8g of methanol, 0.55g of sodium borohydride and 0.003g of triphenylphosphine palladium chloride, reacting for 0.5h, adding 7.6% of phosphoric acid solution to adjust the pH value to 2, then adjusting the pH value to 7 by using 10% of sodium hydroxide solution, standing, layering, drying an organic layer by using anhydrous sodium sulfate, removing the solvent by reducing the pressure, purifying by column chromatography to obtain a light yellow solid, namely the compound 1, 4' -diethyl phosphate methylamino abamectin B1a/B1bContent of it>90％。
The hydrogen spectrum is:1H NMR(CDCl3)δppm:5.95(m,1H),5.85(m,1H),5.80(m,1H),5.68 (m,2H),5.55(dd,J＝0.8,2.6,lH),5.52(d,J＝3.0,1H),5.40(m,lH),4.88(d,J ＝3.2,1H),4.86(br d,J＝13.0,2H),4.70(br d,J＝13.0,2H),4.50(s,lH),4.33(br q, J＝6.7,lH),4.20-3.95(m,4H),3.98(d,J＝6.2,lH),3.84(br s,lH),3.78(m,1H),3.67 (m,1H),3.60(dq,J＝11.1,6.2,2H),3.57(ddd,J＝11.5,5.0,3.8,lH),3.54(s,3H), 3.51(dd,J＝9.9,1.3,lH),3.50(s,3H),3.49(8,3H),3.40(m,lH),3.30(br s,1H), 3.18(dd,J＝9.1,8.7,lH),2.75(br d,J＝3.8,lH),2.41-2.15(m,2H),2.05-1.90(m, 2H),1.90(br s,3H),1.80(m,lH),1.65-1.51(m,6H),1.50(brs,2H),1.47(d,J＝6.7, 3H),1.30(m,6H),1.27(d,J＝6.2,3H),1.19(d,J＝7.0,3H),1.15(d,J＝7.6,3H), 0.99-0.88(m,9H),0.80(m,1H).
LC-MS[M+H]+: 1022.56. 4' -phosphoric acid diethyl ester methylamino abamectin B1aLC-MS [ M + H ] of]+The calculated values are: 1022.56.
the product contains a small amount of 4' -phosphoric acid diethyl ester methylamino abamectin B1bLC-MS [ M + H ] thereof]+The values are: 1008.54.
EXAMPLE 2 Compound 1, 4' -diethoxymethymethylaminefactam B2a/B2bPreparation of
5g of 5-allyloxycarbonyl-4' -carbonyl abamectin B2a/B2b(content of>90%) of the mixture is dissolved in 20g of sec-butyl acetate, 5g of heptamethyldisilazane, 3g of diethyl phosphite and 1.2g of zinc trifluoroacetate are sequentially added, the mixture is stirred while keeping the temperature at 50 ℃ and reacts for 2 hours, the temperature is reduced to minus 10 ℃, 8g of methanol, 0.6g of sodium borohydride and 0.003g of triphenylphosphine palladium chloride are added, and the reaction is carried out for 0.5 hour; adding 7.6% phosphoric acid solution to adjust pH to 2, adjusting pH to 7 with 10% sodium hydroxide solution, standing, layering, drying organic layer with anhydrous sodium sulfate, removing solvent under reduced pressure, and purifying by column chromatography to obtain light yellow solid, i.e. compound 1, 4' -diethyl phosphate methylamino avermectin B2a/B2bContent of it>90％。
The hydrogen spectrum is:1H NMR(CDCl3)δppm:5.95(m,1H),5.91(m,1H),5.85(m,1H), 5.45(dd,J＝0.8,2.6,lH),5.42(d,J＝3.0,1H),5.30(m,lH),4.78(d,J＝3.2,1H), 4.66(br d,J＝13.0,2H),4.60(br d,J＝13.0,2H),4.10(s,lH),4.03(br q,J＝6.7,lH), 4.00-3.90(m,4H),3.88(d,J＝6.2,lH),3.84(br s,lH),3.78(m,1H),3.67(m,1H), 3.60(dq,J＝11.1,6.2,2H),3.57(ddd,J＝11.5,5.0,3.8,lH),3.54(s,3H),3.52(m, lH),3.51(dd,J＝9.9,1.3,lH),3.50(s,3H),3.48(8,3H),3.38(m,lH),3.36(q,J＝ 2.0,lH),3.21(br s,1H),3.13(dd,J＝9.1,8.7,lH),2.71(br d,J＝3.8,lH),2.31-2.25 (m,2H),2.05-1.90(m,2H),1.89(br s,3H),1.78(m,lH),1.72(d,J＝4.1, 2H),1.65-1.46(m,6H),1.42(brs,2H),1.40(d,J＝6.7,3H),1.29(m,6H),1.23(d,J ＝6.2,3H),1.16(d,J＝7.0,3H),1.10(d,J＝7.6,3H),0.96-0.91(m,9H),0.89(m,1H).
LC-MS[M+H]+: 1040.56. 4' -phosphoric acid diethyl ester methylamino abamectin B2aLC-MS [ M + H ] of]+The calculated values are: 1040.56.
the product contains a small amount of 4' -phosphoric acid diethyl ester methylamino abamectin B2bLC-MS [ M + H ] thereof]+The values are: 1026.55.
EXAMPLE 3 Compound 2, 4' -diethoxyphosphoate Abamectin B2a/B2bPreparation of
5g of 5-allyloxycarbonyl-4' -carbonyl abamectin B2a/B2b(content of>90%) of the compound, 0.7g of diethyl phosphite and 0.5g of triethylamine are sequentially added, the temperature is kept for 2h at the temperature of 50 ℃, the temperature is reduced to minus 10 ℃, 8g of methanol, 0.6g of sodium borohydride and 0.003g of triphenylphosphine palladium chloride are added for reaction for 0.5h, then 7.6% of phosphoric acid solution is added for regulating the pH value to 2, then 10% of sodium hydroxide solution is used for regulating the pH value to 7, the mixture is kept stand and layered, dried by anhydrous sodium sulfate, the solvent is removed by decompression, and light yellow solid can be obtained by column chromatography purification, namely the compound 2, 4' -diethyl phosphate hydroxy abamectin B2a/B2bContent of it>90％。
The hydrogen spectrum is:1H NMR(CDCl3)δppm:5.84-5.95(m,3H),5.55(dd,J＝0.8,2.6, lH),5.47(d,J＝3.0,1H),5.40(m,lH),4.70(d,J＝3.2,1H),4.79(br d,J＝13.0,2H), 4.66(br d,J＝13.0,2H),4.30(s,lH),4.23(br q,J＝6.7,lH),4.10-3.90(m,4H),3.98 (d,J＝6.2,lH),3.88(br s,lH),3.81(m,1H),3.74(m,1H),3.70(s,1H),3.69(dq,J＝ 11.1,6.2,2H),3.67(ddd,J＝11.5,5.0,3.8,lH),3.54(s,3H),3.52(m,lH),3.51(dd,J ＝9.9,1.3,lH),3.50(s,3H),3.58(m,lH),3.46(q,J＝2.0,lH),3.33(dd,J＝9.1,8.7, lH),2.91(br d,J＝3.8,lH),2.51-2.55(m,2H),2.25-1.99(m,2H),1.89(br s,3H), 1.78(m,lH),1.76(d,J＝4.1,2H),1.65-1.46(m,6H),1.42(brs,2H),1.40(d,J＝6.7, 3H),1.29(m,6H),1.27(d,J＝6.2,3H),1.20(d,J＝7.0,3H),1.15(d,J＝7.6,3H), 0.99-0.90(m,9H),0.83(m,1H).
LC-MS[M+H]+: 1027.53. 4' -diethoxy hydroxy avermectin B phosphate2aLC-MS [ M + H ] of]+The calculated values are: 1027.53.
the product contains a small amount of 4' -phosphodiethoxy hydroxy abamectin B2bLC-MS [ M + H ] thereof]+The values are: 1013.51.
EXAMPLE 4 Compound 3, 5-hydroxyaminoidene-4' -phosphodiethoxymetamido-avermectin B1a/B1bPreparation of
5g of compound 5-hydroxyaminolidene-4' -carbonyl abamectin B2a/B2b(content of>90%) of the compound, is dissolved in 20g of sec-butyl acetate, 5g of heptamethyldisilazane, 3.3g of diphenyl phosphite and 0.1g of trichloroethyl aluminum are added, the temperature is kept for 2 hours at the temperature of 50 ℃, 7.6% of phosphoric acid solution is added to adjust the pH value to 2, then 10% of sodium hydroxide solution is added to adjust the pH value to 7, the mixture is kept stand and layered, anhydrous sodium sulfate is used for drying, the solvent is removed by decompression, and the solid is obtained by column chromatography extraction, namely the compound 3, 5-hydroxyamino subunit-4' -phosphoric acid diethyl methylamino abamectin B1a/B1bIn a content of>90％。
LC-MS[M+H]+: 1035.55. 5-hydroxyamino-4' -phosphodiethoxymethnemine avermectin B1aLC-MS [ M + H ] of]+The calculated values are: 1035.55.
the product contains a small amount of 5-hydroxyamino-4' -phosphodiethyl methylamino abamectin B1bLC-MS [ M + H ] thereof]+The values are: 1021.53.
EXAMPLE 5 Compound 4, 4' -Diisopropyloxycarbonylhydroxyavermectin B2a/B2bAnd (4) preparing.
5g of 5-allyloxycarbonyl-4' -carbonyl abamectin B2a/B2b(content of>90%) of the crude extract is dissolved in 20g of dichloromethane, 0.7g of diisopropyl phosphite and 0.5g of tetramethylethylenediamine are added, the temperature is kept for 2h at the temperature of 50 ℃, the temperature is reduced to-10 ℃, 8g of methanol, 0.6g of sodium borohydride and 0.003g of triphenylphosphine palladium chloride are added for reaction for 0.5h, 7.6% of phosphoric acid solution is added for adjusting the pH to 2, 10% of sodium hydroxide solution is used for adjusting the pH to 7, the mixture is kept stand and layered, anhydrous sodium sulfate is used for drying, the solvent is removed under reduced pressure, and light yellow solid is obtained by column chromatography purification, namely the compound 4, 4' -diisopropyl phosphate hydroxy abamectin B2a/B2bContent of it>90％。
LC-MS[M+H]+: 1055.56. 4' -diethoxy hydroxy avermectin B phosphate2aLC-MS [ M + H ] of]+The calculated values are: 1055.56.
the product contains a small amount of 4' -phosphodiethoxy hydroxy abamectin B2bLC-MS [ M + H ] thereof]+The values are: 1041.55.
Comparative example 1 Avermectin derivative prepared by the preparation method disclosed in Chinese patent application 201310063563.0
Comparative example 2 Avermectin derivative prepared by the preparation method disclosed in Chinese patent application 201410721599.8
Comparative example 3 Abamectin B1a/B1b
Comparative example 4 Abamectin B2a/B2b
Test of drug efficacy
(1) All samples are diluted by water and then sprayed for use, when the target pests are rice stem borers, the using amount of the effective ingredients is 200 g/hectare, and the drug effect comparison condition is as shown in the following table 1:
the field test shows that the insecticidal effect of the avermectin derivative prepared in the embodiments 1-5 of the invention on the target rice stem borer is better than that of the comparative examples 1-4 and better than that of the avermectin B1a/B1bIs also obviously superior to abamectin B2a/B2bThe invention proves that the prepared organophosphorus group substituted avermectin derivative has good insecticidal effect on the target rice stem borer.
(2) All samples are diluted by water and sprayed for use, when the target pests are rice planthoppers, the using amount of the active ingredients is 80 g/hectare, and the drug effect comparison condition is shown in the following table 1:
the field test shows that the control effect of the avermectin derivative prepared in the embodiments 1-5 of the invention on rice planthopper is better than that of the comparative examples 1-4 and better than that of the avermectin B1a/B1bIs also obviously superior to abamectin B2a/B2bThe invention proves that the prepared organophosphorus group substituted avermectin derivative has good insecticidal effect on rice planthopper.
(3) All samples are diluted by water and sprayed for use, when the target pest is citrus red spider, the using amount of the active ingredients is 10 g/hectare, and the drug effect comparison condition is as shown in the following table 1:
the field test shows that the insecticidal effect of the avermectin derivative prepared in the embodiments 1-5 of the invention on citrus red spiders is better than that of the comparative examples 1-4 and better than that of the avermectin B1a/B1bIs also obviously superior to abamectin B2a/B2bIn 14 days after the pesticide effect, the death rate of the pests of the avermectin derivatives substituted by the organophosphorus groups prepared in the embodiments 1-5 is up to more than 75 percent, which is obviously superior to that of the avermectin derivatives prepared in the comparative examples 1-4, and the avermectin derivatives substituted by the organophosphorus groups prepared by the invention have good pesticidal effect on citrus red spiders.
The preferred embodiments of the present invention have been described in detail, however, the present invention is not limited to the specific details of the above embodiments, and various simple modifications may be made to the technical solution of the present invention within the technical idea of the present invention, and these simple modifications are within the protective scope of the present invention. It should be noted that the various technical features described in the above embodiments can be combined in any suitable way without contradiction, and the invention is not described in any way for the possible combinations in order to avoid unnecessary repetition. In addition, any combination of the various embodiments of the present invention is also possible, and the same should be considered as the disclosure of the present invention as long as it does not depart from the spirit of the present invention.
Claims (10)
1. An organophosphorus group substituted avermectin derivative, which is characterized in that: the avermectin derivative has a chemical structural general formula shown in a formula (I);
wherein:
R1is methyl or ethyl; X-Y is CH2-CH(OH)；
R2Is an oxygen atom;
R3and R4Each independently selected from C1-C8 alkyl;
R5is a hydroxyl group.
2. The organophosphorus group-substituted avermectin derivative of claim 1, wherein: the organophosphorus substituted avermectin derivative can be used for preventing and controlling plant pests; the prevention and treatment effect of the organophosphorus substituted avermectin derivative on pests is better than that of avermectin B1a/B1bAnd abamectin B2a/B2b。
3. An organophosphorus group-substituted avermectin derivative according to claim 2, wherein: the plant pests are selected from one or more of target rice stem borers, citrus red spiders and rice planthoppers.
4. A process for the preparation of an organophosphorus group-substituted avermectin derivative as claimed in claim 1, which comprises: the method comprises the following four reaction modes:
(1) reacting a starting material compound (II) with an organic phosphorus-containing reagent in an inert solvent at the temperature of 60-100 ℃ in the presence of a basic catalyst to obtain a compound shown as a formula (III);
(2) reacting an initial raw material compound (II), an amination reagent and an organophosphorus-containing reagent in an inert solvent at the temperature of 80-100 ℃ in the presence of an amination catalyst to obtain a compound shown in a formula (IV);
(3) reacting a starting raw material compound (II) with an organophosphorus-containing reagent in an inert solvent at the temperature of 100-120 ℃ in the presence of an amination reagent, an amination catalyst and a basic catalyst to obtain a compound shown in a formula (V);
(4) reacting the compounds shown in the formulas (III), (IV) and (V) with a deprotection catalyst in an inert solvent at the temperature of-20-5 ℃ to obtain the compound shown in the formula (I),
wherein R is8Is a hydroxyl protecting group.
5. The process for producing an organophosphorus group-substituted avermectin derivative according to claim 4, wherein: the inert solvent is one or more selected from dichloromethane, dichloroethane, 1, 2-dichloroethane, sec-butyl acetate, methanol and ethanol, and the dosage of the inert solvent is 1.0-5.3 times of the weight of the compound (II).
6. The process for producing an organophosphorus group-substituted avermectin derivative according to claim 4, wherein: the amination reagent is selected from any one of triethanolamine, heptamethyldisilazane, hexamethyldisilazane, methyl amine methanol solution, tetraethylenepentamine and ethylenediamine, and the dosage of the amination reagent is 1.0-2 times of the molar weight of the compound (II).
7. The process for producing an organophosphorus group-substituted avermectin derivative according to claim 4, wherein: the organic phosphorus-containing reagent is any one of diethyl phosphite, diisopropyl phosphite, dibenzyl phosphite, diphenyl phosphite and dibutyl phosphite, and the dosage of the organic phosphorus-containing reagent is 1.0-2 times of the molar quantity of the compound (II).
8. The process for producing an organophosphorus group-substituted avermectin derivative according to claim 4, wherein: the alkaline catalyst is one or a mixture of more of triethylamine, tributylamine, ethyldiisopropylamine and tetramethylethylenediamine in any proportion, and the dosage of the alkaline catalyst is 0.5-1.0 times of the molar weight of the compound (II).
9. The process for producing an organophosphorus group-substituted avermectin derivative according to claim 4, wherein: the amination catalyst is one or a mixture of more of zinc trifluoroacetate, zinc acetate, zinc chloride, trichloroethyl aluminum, triethyl aluminum, tetrabutyl titanate and tetraethyl titanate in any proportion, and the dosage of the amination catalyst is 0.5-5% of the molar weight of the compound (II).
10. The process for producing an organophosphorus group-substituted avermectin derivative according to claim 4, wherein: the deprotection catalyst is one or more of palladium acetate, palladium chloride and triphenylphosphine palladium chloride, and the dosage of the deprotection catalyst is 0.01-0.1% of the molar amount of the compound (II).
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