Abamectin B2a derivative as well as preparation method and application thereof

Abstract

The invention provides an abamectin B2a derivative as well as a preparation method and application thereof, and belongs to the technical field of pesticides, the structure of the abamectin B2a derivative is as shown in a formula I: # imgabs0 #, r2 is ortho-and para-substituted phenyl # imgabs1 # R3, R4 is H, F, Br, Cl and CF3 or # imgabs2 # R5 is methyl or ethyl. A series of compounds are obtained by modifying the 4 ''site of the abamectin B2a, and the compound is stable in structure, has special effects on armyworms, plutella xylostella, mites and underground nematodes, has a good control effect on resistant pests, is long in lasting period, and has important significance on effective utilization of the abamectin B2a.

Description

Technical Field

[0001] The present invention relates to an avermectin B2a derivative, in particular to an avermectin B2a derivative and a preparation method and application thereof, belonging to the technical field of pesticides. Background Art

[0002] In recent years, avermectin has been widely used in agricultural production as a highly effective, low-toxic pesticide. Its excellent insecticidal properties have been highly recognized by the industry and users. Technical researchers have continuously modified its structure and obtained new structural derivatives with good efficacy. CN113150053 A modified the 4" position of avermectin and disclosed azobenzene avermectin derivatives and their preparation methods and applications. Wuhan University CN03833811A disclosed the synthesis of avermectin with an oxime at the 5" position. Lanzhou University introduced an isonitrile group into the 4" position of avermectin and disclosed its insecticidal effect against pine wood nematodes.

[0003] Due to the strong market demand for avermectin, manufacturers are continuously expanding their production capacity, resulting in an increasing amount of avermectin B2a produced during the fermentation process. While avermectin B2a has some insecticidal effects, it is sensitive to light and heat, is very unstable, and cannot be effectively utilized, resulting in a waste of resources. Summary of the Invention

[0004] In response to the above problems, the present invention provides an avermectin B2a derivative and a preparation method and application thereof, so as to better and effectively utilize avermectin B2a.

[0005] To achieve the above object, the technical solution of the present invention is:

[0006] An avermectin B2a derivative, the structure of which is shown in Formula I:

[0007]

[0008] Where: R 1 is methyl or ethyl;

[0009] R 2 Phenyl substituted at the ortho or para position R 3 、R 4 H, F, Br, Cl, CF3 or R 5 It is methyl or ethyl.

[0010] Furthermore, R 2 The structure is selected from the following groups:

[0011] The preparation method of the above-mentioned avermectin B2a derivative comprises the following steps:

[0012] (1) Using a substituted primary amine as a starting material, it reacts with phenyl chloroformate in the presence of an acid binding agent to obtain a compound as shown in Formula II, which is then reacted with hydrazine hydrate to obtain a hydrazide compound as shown in Formula III; the reaction equation is as follows:

[0013]

[0014] (2) Formula III and 5-protected-4"-carbonyl avermectin as shown in Formula IV react to produce Formula V; the reaction equation is as follows:

[0015]

[0016] (3) The 5-position protecting group of formula V is removed to generate the target product of formula I. The reaction equation is as follows:

[0017]

[0018] Furthermore, in step (1), the reaction solvent is an alcohol, a halogenated hydrocarbon or an ester, the reaction temperature of the reaction process to obtain Formula II is 0-5°C, the acid binding agent is an inorganic base, the hydrazine hydrate is 100% hydrazine hydrate, and the reaction temperature after adding hydrazine hydrate is reflux.

[0019] Furthermore, in step (1), the reaction solvent is methanol, ethanol or acetonitrile; the acid binding agent is sodium bicarbonate or sodium carbonate; and the molar ratio of the primary amine, phenyl chloroformate and hydrazine hydrate is 1.0:1.0-1.5:1.5-2.0.

[0020] Furthermore, in step (2), the reaction solvent is an alcohol, a halogenated hydrocarbon or toluene; the molar feed ratio of III to formula IV is 1.0-1.2:1.0; the reaction temperature is 20-100°C; the compound represented by formula IV is prepared by using avermectin B2a as a raw material, dichloromethane, toluene or sec-butyl acetate as a solvent, reacting with a hydroxyl protecting agent at low temperature in the presence of an organic base to obtain 5-protected avermectin B2a, which is then reacted with an oxidant without separation.

[0021] Furthermore, in step (2), the reaction solvent is dichloromethane or toluene; the reaction temperature is 40-60°C; the organic base is tetramethylethylenediamine, the low temperature is -20°C, the hydroxyl protecting agent is allyl chloroformate or alkylchlorosilane protecting agent, and the oxidant is dimethyl sulfoxide or phosphorus oxychloride.

[0022] Furthermore, in step (3), the compound of formula V is directly subjected to a deprotection reaction without separation; if the protecting group is an allyl carbonate, tetrakistriphenylphosphine palladium is added as a catalyst, and the protecting agent is removed under the action of sodium borohydride; if the protecting group is a silicon-based protecting group, the reaction solution is adjusted to an acidic state to remove the protecting group.

[0023] Furthermore, in step (3), if the protecting group is allyl carbonate, the deprotection temperature is -10°C to 0°C; and the temperature during acid adjustment is -5°C to 0°C.

[0024] The above-mentioned avermectin B2a derivative or the application of the prepared avermectin B2a derivative is used to kill armyworms, diamondback moths, red spiders or underground nematodes.

[0025] The beneficial effects of the avermectin B2a derivative of the present invention and its preparation method and application are as follows:

[0026] The present invention modifies the 4" position of avermectin B2a to obtain a series of compounds with stable structures, special effects on armyworms, diamondback moths, mites, and underground nematodes, good control effects on resistant pests, and long-lasting effects. This effectively expands the scope of use of avermectin B2a and is of great significance for the effective utilization of avermectin B2a. DETAILED DESCRIPTION

[0027] The technical solutions in the embodiments of the present invention are described clearly and completely below. Many specific details are set forth in the following description to facilitate a full understanding of the present invention. However, the present invention may also be implemented in other ways different from those described herein, and those skilled in the art may make similar generalizations without violating the scope of the present invention. Therefore, the present invention is not limited to the specific embodiments disclosed below.

[0028] An avermectin B2a derivative, the structure of which is shown in Formula I:

[0029]

[0030] Where: R 1 is methyl or ethyl;

[0031] R 2 Phenyl substituted at the ortho or para position R 3 、R 4 H, F, Br, Cl, CF3 or R 5 It is methyl or ethyl.

[0032] Furthermore, R 2 The structure is selected from the following groups:

[0033]

[0034] The preparation method of the above-mentioned avermectin B2a derivative comprises the following steps:

[0035] (1) Using a substituted primary amine as a starting material, it reacts with phenyl chloroformate in the presence of an acid binding agent to obtain a compound as shown in Formula II, which is then reacted with hydrazine hydrate to obtain a hydrazide compound as shown in Formula III; the reaction equation is as follows:

[0036]

[0037] The reaction solvent is alcohol, halogenated hydrocarbon or ester, preferably methanol, ethanol or acetonitrile; the reaction temperature of the reaction process to obtain the compound of formula II is 0-5°C; the acid binding agent is an inorganic base, preferably sodium bicarbonate or sodium carbonate; the hydrazine hydrate is 100% hydrazine hydrate; the reaction temperature after adding hydrazine hydrate is reflux; and the molar ratio of the primary amine, phenyl chloroformate and hydrazine hydrate is 1.0:1.0-1.5:1.5-2.0.

[0038] (2) Formula III and 5-protected-4'-carbonyl avermectin as shown in Formula IV are reacted to produce Formula V; the reaction equation is as follows:

[0039]

[0040] The reaction solvent is alcohol, halogenated hydrocarbon or toluene, and the preferred reaction solvent is dichloromethane or toluene; the molar feed ratio of the compounds represented by formula III to formula IV is 1.0-1.2:1.0; the reaction temperature is 20-100°C; the compound represented by formula IV is prepared by using avermectin B2a as a raw material, dichloromethane, toluene or sec-butyl acetate as a solvent, reacting with a hydroxyl protective agent (allyl chloroformate or alkylchlorosilane protective agent) at low temperature (-20°C) under the action of an organic base (tetramethylethylenediamine) to obtain 5-protected avermectin B2a, which is then reacted with an oxidant (dimethyl sulfoxide or phosphorus oxychloride) without separation to obtain the obtained product.

[0041] (3) The 5-position protecting group of formula V is removed to generate the target product of formula I. The reaction equation is as follows:

[0042]

[0043] Furthermore, in step (3), the compound of formula V is directly subjected to a deprotection reaction without separation; if the protecting group is an allyl carbonate, tetrakistriphenylphosphine palladium is added as a catalyst, and the protecting agent is removed under the action of sodium borohydride, and the deprotection temperature is -10°C to 0°C; if the protecting group is a silicon-based protecting group, the reaction solution is adjusted to acidity to remove the protecting group, and the temperature during acidification is -5°C to 0°C.

[0044] The above-mentioned avermectin B2a derivative or the application of the prepared avermectin B2a derivative is used to kill armyworms, diamondback moths, red spiders or underground nematodes.

[0045] Example 1

[0046] An avermectin B2a derivative and a preparation method thereof are as follows:

[0047] Step (1) Synthesis of Formula III

[0048] 0.1 molR 2 -NH2 hydrochloride was dissolved in 100g methanol, 92.0g saturated sodium bicarbonate aqueous solution was added, 0.11mol phenyl chloroformate was slowly added dropwise after cooling to 0°C, the temperature was slowly raised to 20-25°C after addition, kept warm for 2h, filtered, the filter cake was washed with water, and dried to obtain 0.09mol of the solid compound of formula II; 40g methanol was added, 0.16mol hydrazine hydrate was added dropwise, the temperature was raised to reflux after addition, the reaction was continued for 3h, methanol was removed, dichloromethane was added, the aqueous phase was separated, the solvent was removed to obtain a solid, and dried to obtain the compound of formula III. This embodiment R 2 The structure is as follows:

[0049]

[0050] Step (2) Synthesis of 5-protected-4'-carbonyl B2a of Formula IV

[0051] 0.1 mol of avermectin B2a was dissolved in 282 g of dichloromethane. After complete dissolution, the temperature was lowered to -20°C. 0.12 mol of allyl chloroformate was added, and 0.12 mol of tetramethylethylenediamine was slowly added dropwise. When the residual avermectin B2a was less than 1.0%, tetramethylethylenediamine and dimethyl sulfoxide were added, and phosphorus oxychloride was slowly added dropwise. After the reaction was completed, sodium bicarbonate solution was added to terminate the reaction. The dichloromethane layer was separated and desolvated to obtain the compound of formula IV.

[0052] Step (3) Synthesis of the target product compound of formula I

[0053] The compound of formula IV obtained in step (2) is dissolved in 400 g of ethanol, and the compound of formula III obtained in step (1) is added, and the temperature is raised to reflux for reaction for 2 h. After the reaction is completed, some ethanol is removed, and dichloromethane is added to cool to 0°C. 0.02 g of tetrakistriphenylphosphine palladium is added, and 3.8 g of sodium borohydride is slowly added in batches. After the reaction is completed, the mixture is washed twice with water, and the dichloromethane layer is separated and desolventized to obtain the compound of formula I.

[0054]

[0055] The hydrogen spectrum of the compound of formula I is: l H NMR(400.0MHz):7.78(s,1H),7.61(s,1H),7.07(s,1H),7.45(s,1H),6.06(m,2H),5.3(m,3H),5.20(m,lH),4.96(br d,J=3.0,lH),4.46(m,2H),4.40(br d,J=8.1,lH),4.33(br q,J=9.7,lH),4.00(br s,lH),3.98(m,2H),3.88(s,1H),3.80(dq,J=10.3,9.3,lH),3.76(ddd,J=12.5,5.0,4.8,lH),3.7(s,lH),3.68(m,lH),3.55( dd,J=8.8,4.3,lH),3.5(s,3H),3.4(s,3H),3.37(m,lH),3.35(s,1H),3.33(q,J=3.3,lH),3.23(dd,J=12.1,9.6,lH),2.99(br d,J=6.4,lH),2.82(m,lH),2.61-2.75(m,2H),2.51(dd,J=11.6,6.5,lH),2.30-2.45(m,2H),2.17(br s,3H),2.18(m,lH),1.92(d,J=6.1,2H),1.63-1.86(m,5H),1.59(brs,2H),1.5(d,J=6.7,3H),1.43(d, J=8.7,3H),1.40(d,J=6.2,3H),1.32(d,J=7.9,3H),1.3(d,J=9.0,3H),0.96-1.19(m,8H),0.98(m,1H). The liquid molecular weight is: 1040.23.

[0056] Example 2

[0057] An avermectin B2a derivative and a preparation method thereof are as follows:

[0058] Step (1) Synthesis of Formula III

[0059] 0.1 molR 2-NH2 hydrochloride was dissolved in 100g of ethanol, 92.5g of saturated sodium carbonate aqueous solution was added, and 0.1mol of phenyl chloroformate was slowly added dropwise after cooling to 0°C. After the addition, the temperature was slowly raised to 20-25°C, kept warm for 2h, filtered, the filter cake was washed with water, and dried to obtain 0.09mol of the solid compound of formula II; 40.9g of ethanol was added dropwise, 0.2mol of hydrazine hydrate was added dropwise, the temperature was raised to reflux after the addition, and the reaction was carried out for 3h. The ethanol was removed, dichloromethane was added, the aqueous phase was separated, the solvent was removed to obtain a solid, and dried to obtain the compound of formula III. This embodiment R 2 The structure is as follows:

[0060]

[0061] Step (2) Synthesis of 5-protected-4'-carbonyl B2a of Formula IV

[0062] 0.1 mol of avermectin B2a was dissolved in 282 g of toluene. After complete dissolution, the temperature was lowered to -20°C. 0.12 mol of alkylchlorosilane protective agent was added. 0.12 mol of tetramethylethylenediamine was slowly added dropwise. When the residual avermectin B2a was less than 1.0%, tetramethylethylenediamine and dimethyl sulfoxide were added. Phosphorus oxychloride was slowly added dropwise. After the reaction was completed, sodium bicarbonate solution was added to terminate the reaction. The toluene layer was separated and desolventized to obtain the compound of formula IV.

[0063] Step (3) Synthesis of the target product compound of formula I

[0064] The compound of formula IV obtained in step (2) is dissolved in 400 g of ethanol, and the compound of formula III obtained in step (1) is added. The temperature is raised to reflux and the reaction is carried out for 2 h. After the reaction is completed, some ethanol is removed, and dichloromethane is added to cool the mixture to 0°C. The reaction mixture is adjusted to acidic to remove the protecting group. After the reaction is completed, the mixture is washed twice with water, and the dichloromethane layer is separated and desolventized to obtain the compound of formula I.

[0065]

[0066] The hydrogen spectrum of the compound of formula I is: lH NMR(400.0MHz):7.78(s,1H),7.61(s,1H),7.07(s,1H),7.45(s,1H),6.06(m,2H),5.3(m,3H),5.20(m,lH),4.96(br d,J=3.0,lH),4.46(m,2H),4.40(br d,J=8.1,lH),4.33(br q,J=9.7,lH),4.00(br s,lH),3.98(m,2H),3.88(s,1H),3.80(dq,J=10.3,9.3,lH),3.76(ddd,J=12.5,5.0,4.8,lH),3.7(s,lH),3.68(m,lH),3.55( dd,J=8.8,4.3,lH),3.5(s,3H),3.4(s,3H),3.37(m,lH),3.35(s,1H),3.33(q,J=3.3,lH),3.23(dd,J=12.1,9.6,lH),2.99(br d,J=6.4,lH),2.82(m,lH),2.61-2.75(m,2H),2.51(dd,J=11.6,6.5,lH),2.30-2.45(m,2H),2.17(br s,3H),2.18(m,lH),1.92(d,J=6.1,2H),1.63-1.86(m,5H),1.59(brs,2H),1.5(d,J=6.7,3H),1.43(d, J=8.7,3H),1.40(d,J=6.2,3H),1.32(d,J=7.9,3H),1.3(d,J=9.0,3H),0.96-1.19(m,8H),0.98(m,1H). The liquid molecular weight is: 1101.12.

[0067] Example 3

[0068] An avermectin B2a derivative and a preparation method thereof are as follows:

[0069] Step (1) Synthesis of Formula III

[0070] 0.1 molR 2-NH2 hydrochloride was dissolved in 100g methanol, 90g saturated sodium bicarbonate aqueous solution was added, 0.15mol phenyl chloroformate was slowly added dropwise after cooling to 0°C, the temperature was slowly raised to 20-25°C after addition, kept warm for 2h, filtered, the filter cake was washed with water, and dried to obtain 0.09mol of the compound of formula II solid; 42g methanol was added, 0.15mol hydrazine hydrate was added dropwise, the temperature was raised to reflux after addition, the reaction was continued for 3h, methanol was removed, dichloromethane was added, the aqueous phase was separated, the solvent was removed to obtain a solid, and dried to obtain the compound of formula III. This embodiment R 2 The structure is as follows:

[0071]

[0072] Step (2) Synthesis of 5-protected-4'-carbonyl B2a of Formula IV

[0073] 0.1 mol of avermectin B2a was dissolved in 282 g of dichloromethane. After complete dissolution, the temperature was lowered to -20°C. 0.12 mol of allyl chloroformate was added, and 0.12 mol of tetramethylethylenediamine was slowly added dropwise. When the residual avermectin B2a was less than 1.0%, tetramethylethylenediamine and dimethyl sulfoxide were added, and phosphorus oxychloride was slowly added dropwise. After the reaction was completed, sodium bicarbonate solution was added to terminate the reaction. The dichloromethane layer was separated and desolvated to obtain the compound of formula IV.

[0074] Step (3) Synthesis of the target product compound of formula I

[0075] The compound of formula IV obtained in step (2) is dissolved in 400 g of ethanol, and the compound of formula III obtained in step (1) is added, and the temperature is raised to reflux for reaction for 2 h. After the reaction is completed, some ethanol is removed, and dichloromethane is added to cool to 0°C. 0.02 g of tetrakistriphenylphosphine palladium is added, and 3.8 g of sodium borohydride is slowly added in batches. After the reaction is completed, the mixture is washed twice with water, and the dichloromethane layer is separated and desolventized to obtain the compound of formula I.

[0076]

[0077] The hydrogen spectrum of the compound of formula I is: 1H NMR (400.0 MHz): 7.63 (s, 1H), 7.51 (s, 1H), 7.27 (s, 1H), 7.15 (s, 1H), 6.33 (m, 2H), 5.83 (m, 3H), 5.5 (m, 1H), 4.97 (br d, J = 8.3, 1H), 4.77 (m, 2H), 4.53 (br d, J = 9.1, 1H), 4.23 (br q, J = 8.6, 1H), 4.08 (s, 3H), 3.98 (br s,lH),3.89(m,2H),3.84(s,1H),3.81(dq,J=10.3,8.4,lH),3.77(ddd,J=10.5,5.8,4.8,lH),3.70(s,lH),3.61(m,lH),3.53(d d,J=10.4,5.5,lH),3.43(s,3H),3.39(s,3H),3.38(m,lH),3.31(s,1H),3.30(q,J=5.4,lH),3.26(dd,J=11.1,9.7,lH),2.97(br d,J=6.2,lH),2.72(m,lH),2.31-2.55(m,3H),2.26(dd,J=11.3,6.4,lH),2.05-2.19(m,2H),1.88(br s,3H),1.77(m,lH),1.7(d,J=7.4,2H),1.53-1.66(m,5H),1.51(brs,2H),1.4(d,J=7.5,3H),1.35(d,J =8.7,3H),1.32(d,J=8.8,3H),1.3(d,J=9.7,3H),1.21(d,J=6.8,3H),0.93-1.09(m,8H),0.82(m,1H). The liquid molecular weight is: 1079.28.

[0078] Examples 4-15

[0079] The preparation method of the derivatives of Examples 4-15 is basically the same as that of Example 1, except that R 2 The structures are different, and the hydrogen spectrum and liquid-mass-mass molecular weight of the obtained target product are shown in Table 1:

[0080] Table 1

[0081]

[0082]

[0083]

[0084] Test Example 1 Indoor toxicity determination of insecticidal activity of new compounds

[0085] 1. Purpose of the experiment

[0086] The toxicity of the new compound to armyworms, planthoppers and cotton spiders at the tested concentrations was determined indoors to preliminarily evaluate its insecticidal activity and provide scientific guidance for the further research of the new compound.

[0087] 2 Test conditions

[0088] 2.1 Test targets

[0089] Armyworm (Mythimna sepatara) is a sensitive strain that has been reared on fresh corn leaves for many years, and the insects used in the test are third-instar larvae.

[0090] The cotton spider mite (Tetranychus urticae) is a sensitive strain that has been reared indoors on broad bean seedlings for many years. The insects used in the experiment are healthy adult mites.

[0091] 2.2 Culture conditions

[0092] The culture conditions of the test targets and the post-test targets were a temperature of 25±5°C, a relative humidity of 65±5%, and a photoperiod of 12 / 12h (L / D).

[0093] 2.3 Instruments and Equipment

[0094] Electronic balance (sensitivity of 1 part per thousand), spray tower, 100ml beaker, glass test tube, graduated cylinder, Petri dish, Parafilm, sponge, filter paper, pipette, tweezers, brush, microscope, etc.

[0095] 3 Experimental design

[0096] 3.1 Test Agents

[0097] V22801187, avermectin, and the new compound were provided by Hebei Weiyuan Biochemical Co., Ltd.

[0098] 3.2 Test concentration

[0099] Armyworm: 20mg / L; Planthopper: 10mg / L; Cotton red spider: 10mg / L.

[0100] 3.3 Preparation of medicine

[0101] Technical drug: weigh the required amount using a 1 / 10,000 electronic balance;

[0102] Solvent: N,N-dimethylformamide (DMF), 0.2%;

[0103] Emulsifier: Tween 80, 0.2%; add water to dilute to the required concentration.

[0104] 4 Test methods

[0105] Refer to "SOP for Pesticide Biological Activity Evaluation".

[0106] Use the spray method for armyworms. Place uniformly sized corn leaf segments in a Petri dish (90 mm diameter) lined with filter paper, then inoculate 10 third-instar larvae. Place the dish under a Potter spray tower and spray. Use 1 ml / 10 larvae, repeating four times per treatment. After treatment, place the dish in a recovery room. After 72 hours, examine and record any deaths, and calculate the mortality rate.

[0107] The rice stem immersion method was used to test for planthoppers. Fifteen rice seedlings with two leaves and one core were selected and immersed in the test solution for 30 seconds. Afterwards, they were removed and air-dried. The roots were then wrapped with damp absorbent cotton to maintain moisture, covered with plastic wrap, and placed in a glass test tube (200-30 mm). Three replicates were performed for each concentration. A brush was then used to inoculate third-instar nymphs of rice planthoppers, 15 ± 3 per tube, and the tube mouth was tied with white gauze. After treatment, the test tubes were placed in an observation room. After 72 hours, the test insects were inspected for mortality.

[0108] Spraying was used to treat cotton spider mites. Two-leaf, one-heart stage broad bean seedlings infested with adult spider mites were uprooted and placed in a beaker filled with clean water. The beaker was sealed with parafilm and a plastic gasket was inserted. The plants were sprayed with an electric throat sprayer at a rate of 2 ml per plant, with four replicates per treatment. After the plants were air-dried, they were covered with lanterns and placed in a recovery room. After 72 hours, the plants were inspected and any deaths recorded, and the mortality rate was calculated.

[0109] 5 Investigation methods and bioactivity evaluation methods

[0110] 5.1 Survey Methods

[0111] After 72 hours, the death of the test insects was checked and recorded. The criterion for judging the death of the test insects was: if the test insects did not react when gently touched with a brush, they were considered dead.

[0112] 5.2 Biological activity evaluation method

[0113] A mortality rate of more than 90% is grade A, between 70 and 90% is grade B, between 50 and 70% is grade C, and between 0 and 50% is grade D. If activity reaches grade A or B, further screening can be considered.

[0114] 6 Results Analysis and Discussion

[0115] Table 2 Insecticidal activity test results of new compounds (72h)

[0116]

[0117]

[0118] Obviously, the embodiments described are only some of the embodiments of the present invention, not all of them. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative efforts are within the scope of protection of the present invention.

Claims

1. An avermectin B2a derivative, characterized in that: The structure of the avermectin B2a derivative is shown in Formula I: Where: R 1 is methyl or ethyl; R 2 Phenyl substituted at the ortho or para position R 3 , R 4 H, F, Br, Cl, CF3 or R 5 It is methyl or ethyl.

2. An avermectin B2a derivative according to claim 1, characterized in that: R 2 The structure is selected from the following group:

3. The method for preparing an avermectin B2a derivative according to claim 1 or 2, characterized in that: The following steps are involved: (1) Using a substituted primary amine as a starting material, reacting with phenyl chloroformate in the presence of an acid binding agent to obtain a compound as shown in Formula II, and then reacting with hydrazine hydrate to obtain a compound as shown in Formula III; the reaction equation is as follows: (2) Formula III and 5-protected-4"-carbonyl avermectin as shown in Formula IV are reacted to produce Formula V; the reaction equation is as follows: (3) The 5-position protecting group of formula V is removed to generate the target product of formula I. The reaction equation is as follows:

4. The method for preparing an avermectin B2a derivative according to claim 3, characterized in that: In step (1), the reaction solvent is alcohol, halogenated hydrocarbon or ester, the reaction temperature of the reaction process of obtaining formula II is 0-5°C, the acid binding agent is an inorganic base, the hydrazine hydrate is 100% hydrazine hydrate, and the reaction temperature after adding hydrazine hydrate is reflux.

5. The method for preparing an avermectin B2a derivative according to claim 4, characterized in that: In step (1), the reaction solvent is methanol, ethanol or acetonitrile; the acid binding agent is sodium bicarbonate or sodium carbonate; and the molar ratio of the primary amine, phenyl chloroformate and hydrazine hydrate is 1.0:1.0-1.5:1.5-2.

0.

6. The method for preparing an avermectin B2a derivative according to claim 3, characterized in that: In step (2), the reaction solvent is alcohol, halogenated hydrocarbon or toluene; the molar feed ratio of the compounds represented by formula III to formula IV is 1.0-1.2:1.0; the reaction temperature is 20-100°C; the compound represented by formula IV is prepared by using avermectin B2a as a raw material, using dichloromethane, toluene or sec-butyl acetate as a solvent, reacting with a hydroxyl protective agent at low temperature under the action of an organic base to obtain 5-protected avermectin B2a, which is then reacted with an oxidant without separation to obtain the obtained product.

7. The method for preparing an avermectin B2a derivative according to claim 6, characterized in that: In step (2), the reaction solvent is dichloromethane or toluene; the reaction temperature is 40-60°C; the organic base is tetramethylethylenediamine, the low temperature is -20°C, the hydroxyl protecting agent is allyl chloroformate or alkylchlorosilane protecting agent, and the oxidant is dimethyl sulfoxide or phosphorus oxychloride.

8. The method for preparing an avermectin B2a derivative according to claim 3, characterized in that: In step (3), the compound of formula V does not need to be separated and is directly subjected to a deprotection reaction; if the protecting group is an allyl carbonate, tetrakistriphenylphosphine palladium is added as a catalyst and the protecting agent is removed under the action of sodium borohydride; if the protecting group is a silicon-based protecting group, the reaction solution is adjusted to an acidic state to remove the protecting group.

9. The method for preparing an avermectin B2a derivative according to claim 8, characterized in that: In step (3), if the protecting group is allyl carbonate, the deprotection temperature is -10°C to 0°C; the temperature during acid adjustment is -5°C to 0°C.

10. Use of an avermectin B2a derivative according to claim 1-2 or an avermectin B2a derivative prepared according to claim 3-9, characterized in that: The avermectin B2a derivative is used for killing armyworms, diamondback moths, red spiders or underground nematodes.

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