CN111269281A

CN111269281A - Abamectin B2a derivative and preparation method and application thereof

Info

Publication number: CN111269281A
Application number: CN202010122821.8A
Authority: CN
Inventors: 张建军; 许庆博; 李金明; 张江波
Original assignee: Inner Mongolia Jumbo Biotechnology Co ltd; China Agricultural University
Current assignee: Inner Mongolia Jumbo Biotechnology Co ltd; China Agricultural University
Priority date: 2020-02-27
Filing date: 2020-02-27
Publication date: 2020-06-12
Anticipated expiration: 2040-02-27
Also published as: WO2021169606A1; CN111269281B; BR112022015136A2

Abstract

The invention discloses an avermectin B2a high-alkene derivative and a preparation method and application thereof. The structural formula of the avermectin B2a high-alkene derivative is shown as a formula I. The compound has high-efficiency insecticidal activity on a plurality of targets, and is particularly used for preventing and treating crop beet armyworm, plutella xylostella, root-knot nematode and other insecticidal activities.

Description

Abamectin B2a derivative and preparation method and application thereof

Technical Field

The invention belongs to the field of agricultural organic chemistry, and particularly relates to novel 4' -substituted derivatives (short as abamectin B2a high-alkene derivatives) with ethylenic bonds at 2, 3-positions and 23, 24-positions in an abamectin B2a structure, a preparation method thereof and application thereof as a pesticide.

Background

Abamectin is a widely used agricultural or veterinary bactericide, insecticide and acaricide, also called amitriptin. The avermectin is a sixteen-element macrolide compound with the activities of sterilization, disinsection, acaricidal and nematicidal, which is firstly developed by Dacun Zhi and the like of North-Ri-Japan university and Merck company in America, and is produced by fermenting Streptomyces Avermitilis in Streptomyces Avermitilis. The abamectin contains 8 structurally similar components A1a, A2a, A1B, A2B, B1a, B2a, B1B and B2B, wherein the biological activity of the component B is far better than that of the component A. The abamectin pesticide bulk drug sold commercially at present is calibrated by taking abamectin B1a as a main effective component (wherein B1a is not less than 90 percent, Bla/Blb >20) and the mass fraction of B1 a. In the production process of avermectin B1a, in order to obtain high-purity avermectin B1a, component B2a with low control effect on target pests is separated and discarded as a byproduct, and the chemical structures of B1a and B2a are as follows (J.Am.chem.Soc.1981,103, 4216-4221):

as can be seen from the molecular structure, the chemical structure difference between B1a and B2a is in the following two aspects (the dotted box in the upper figure is particularly marked): first, the 22, 23-position of B1a is an olefinic bond, and the 22, 23-position of B2a is a saturated single bond; secondly, the 23-position of B1a does not contain hydroxyl (OH), while the 23-position of B2a contains a hydroxyl (OH), the slight difference of the chemical structures causes the great difference of the biological activities of the two, B1a becomes a pesticide widely used in the market due to the high-efficiency broad-spectrum insecticidal activity, and B2a becomes a fermentation byproduct with extremely low commercial value. Therefore, structural modification is carried out on the natural fermentation byproduct B2a, and a compound with higher biological activity than B2a is searched, so that the method has important significance for efficient utilization of B2a and creation of new drugs.

Disclosure of Invention

The invention relates to a novel derivative (called avermectin B2a high alkene derivative for short) shown in formula I, wherein the positions 2, 3-and 23, 24-of avermectin B2a are olefinic bonds, and 4' -is substituted, a preparation method thereof and an insecticidal composition which comprises at least one compound of the novel derivative as an active ingredient. The invention also relates to a preparation method of the composition, and application of the novel compound and the composition in preventing and treating harmful diseases and pests, in particular to insecticidal activity of preventing and treating crop beet armyworm, plutella xylostella, root-knot nematode and the like.

The structural general formula of the avermectin B2a high-alkene derivative is shown as the formula (I):

in the formula (I), R is selected from any one of the following groups: hydroxy (Ia), amino (Ib), NHR₁(Ⅰc)、NHCOR₂(Ⅰd)；

Wherein: NHR₁And NHCOR₂In the radical R₁、R₂Is defined as follows:

r1 and R2 are the same or different and each independently represents: C1-C6 alkyl substituted or unsubstituted by halogen or C1-C3 alkyl, C3-C6 alkenyl substituted or unsubstituted by halogen or C1-C3 alkyl, and C3-C6 alkynyl substituted or unsubstituted by halogen or C1-C3 alkyl.

Depending on the number of carbon atoms indicated, the alkyl group by itself or as part of another substituent will be the following group: for example, methyl, ethyl, propyl, butyl, pentyl, hexyl and the like and their isomers such as isopropyl, isobutyl, tert-butyl, isopentyl and the like. Throughout the specification, halogen means fluorine, chlorine, bromine and iodine, and fluorine, chlorine and bromine are preferably selected. C3-C6 alkenyl refers to unsaturated aliphatic groups containing 1 or more double bonds, such as: 1-propenyl, allyl, 1-butenyl, 2-butenyl, 3-butenyl, CH3CH ═ CHCH ═ CH-, and the like. C3-C6 alkynyl means an unsaturated aliphatic radical containing up to 6 carbon atoms, such as: propargyl, 2-butynyl, 3-butynyl, and the like.

In general, the compounds of formula (I) are stable white solids which have high-value insecticidal activity and can be used for controlling pests in agriculture and other related fields, and the compounds of formula (I) have good insecticidal activity in a wide range of concentrations.

Among the compounds of formula (i) bearing the R substituent groups defined above, the following compounds are of great importance because of their particularly excellent pesticidal properties:

4' -hydroxy abamectin B2a high alkene derivative compound (compound Ia, compound R in formula I is hydroxyl);

4' -amino abamectin B2a high alkene derivative compound (compound Ib, compound of formula I, R is amino);

4' -methylamino abamectin B2a high alkene derivative compound (compound IC 1, in formula I, R is NHR₁And R is₁A compound that is methyl);

4' -Ethylaminoavermectin B2a high-alkene derivative compound (compound IC 2, in formula I, R is NHR₁And R is₁A compound that is ethyl);

4' -acetamido abamectin B2a high alkene derivative compound (compound Id1, in formula I, R is NHCOR₂And R is₂A compound that is methyl);

4' -propionyl amino avermectin B2a high alkene derivative compound (compound Id2, in formula I, R is NHCOR₂And R is₂A compound that is ethyl).

The avermectin B2a high-alkene derivative is also acceptable in the agricultural pharmacy, and the salt can be organic acid salt or inorganic acid salt, such as benzoate, substituted benzoate, citrate, lactate, aldonic acid salt, hydrochloride or sulfate.

In addition, the first compounds indicated above (compounds Ia) are of particular interest as intermediates for the further synthesis of pesticidal substances.

In another aspect, the invention provides a method of synthesizing a compound of formula (I) as described above:

wherein, the method comprises the following steps:

A) in an organic solvent, in the presence of an alkaline medium, reacting abamectin B2a with a protective reagent, namely, dilute propyl chloroformate, at the temperature of-30 ℃, so that hydrogen in C5-OH and 4' -OH in abamectin B2a is replaced by allyloxycarbonyl to obtain a compound shown as a formula (II); (the reaction scheme is shown in FIG. 1)

B) Dehydrating and eliminating C23-OH and C24-H in the compound shown in the formula (II) in the presence of an organic base, an eliminating reagent and an eliminating catalyst to form an olefinic bond, and isomerizing the olefinic bond between C3 and C4 into C2 and C3 olefinic bonds to obtain the compound shown in the formula (III); (see FIG. 2 for a reaction scheme)

C) Reacting a compound shown in a formula (III) with sodium borohydride in an organic solvent in the presence of a catalyst of palladium tetratriphenylphosphine to obtain a compound shown in a formula (Ia); (see FIG. 3 for a reaction scheme)

The compound shown in the formula (Ia) is a compound defined when R in the formula (I) is hydroxyl.

Further, the compounds represented by the formula (ic) and the formula (Ib) can be prepared using the compound represented by the formula (Ia) as an intermediate.

D) Reacting a compound shown in a formula (Ia) with a protecting reagent of allyl chloroformate in an organic solvent in the presence of an alkaline medium to replace hydrogen in C5-OH in the formula (Ia) with allyloxycarbonyl to obtain a compound shown in a formula (IV); (see FIG. 4 for a reaction scheme)

E) Reacting the formula (IV) with an oxidizing reagent dimethyl sulfoxide and acyl chloride in an organic solvent in the presence of alkali to oxidize a C4' -hydroxyl in the formula (IV) into a carbonyl group to obtain a compound shown in the formula (V); (see FIG. 5 for a reaction scheme)

F) Reacting formula (V) with an alkyl amine (R) in an organic solvent under the catalysis of Lewis acid₁NH₂) Reacting to ensure that C4 '-carbonyl in the formula (V) is aminated to C4' -alkylene amino, and then adding reducing agent sodium borohydride to ensure that C4 '-alkylene amino is reduced to C4' -alkylamino, thus obtaining the compound shown in the formula (VI); (see FIG. 6 for a reaction scheme)

Wherein R is₁NH₂And R in the formula (VI)₁Is as defined in formula I;

G) reacting a compound shown in a formula (VI) with sodium borohydride in an organic solvent in the presence of palladium triphenylphosphine as a catalyst to remove a protective group Alloc of C5-OH to obtain a compound shown in a formula (ic); (see FIG. 7 for a reaction scheme)

The compound shown as the formula (IC) is the compound shown as the formula (I) in which R is NHR₁A compound as defined above.

Or:

H) reacting the compound shown in the formula (V) with hexamethyldisilazane in an organic solvent under the catalysis of Lewis acid to ensure that C4 '-carbonyl in the formula (V) is aminated to C4' -imino, and then adding methanol and a reducing agent sodium borohydride to ensure that C4 '-imino is reduced to C4' -amino to obtain the compound shown in the formula (VII); (see FIG. 8 for a reaction scheme)

I) In an organic solvent, in the presence of a catalyst of palladium tetratriphenylphosphine, reacting a compound shown as a formula (VII) with sodium borohydride, and removing a protecting group Alloc of C5-OH to obtain a substance shown as a formula (Ib); (see FIG. 9 for a reaction scheme)

The compound (Ib) is a compound defined when R in the formula (I) is amino.

Or:

J) reacting the formula (VII) with an acylating reagent anhydride or acyl chloride in an organic solvent in the presence of alkali to perform acylation reaction on C4' -amino in the formula (VII) to obtain a compound shown in a formula (VIII); (see FIG. 10 for a reaction scheme)

Wherein R in the formula (VIII)₂Is as defined in formula I;

K) reacting a compound shown in a formula (VIII) with sodium borohydride in an organic solvent in the presence of a catalyst of tetratriphenylphosphine palladium to remove a protective group Alloc of C5-OH to obtain a substance shown in a formula (id):

the compound shown as the formula (Id) is the compound shown as the formula (I), wherein R is NHCOR₂A compound as defined above.

When R in the compound of formula (I) is amino (compound Ib) or alkylamino (compound ic), the invention also provides a method for preparing the salt of the compound Ib and ic.

The method for preparing salified compounds Ib and ic comprises the following steps: dissolving the compound Ib or ic in an organic solvent, adding a salifying reagent, concentrating and drying to obtain a salified product of the corresponding target derivative.

Wherein the organic solvent is at least one of common organic solvents such as dichloromethane, dichloroethane, chloroform, tetrahydrofuran and ethyl acetate; the salifying reagent is organic acid or inorganic acid such as benzoic acid, substituted benzoic acid, citric acid, lactic acid, aldonic acid, hydrochloric acid or sulfuric acid.

In step a) of the above process, the organic solvent is at least one selected from the group consisting of dichloromethane, 1, 2-dichloroethane, isopropyl acetate, ethyl acetate, n-hexane, benzene, toluene, chloroform, tetrachloromethane, petroleum ether, chlorobenzene, dioxane and tetrahydrofuran, preferably at least one selected from the group consisting of dichloromethane, 1, 2-dichloroethane and isopropyl acetate, most preferably dichloromethane; the amount of the organic solvent used may be 1 to 100L, preferably 2 to 10L, more preferably 3 to 5L, and particularly 4L, relative to 1 mole of abamectin B2 a.

Wherein the alkaline medium is selected from at least one of pyridine, triethylamine, ethylenediamine, tetramethylethylenediamine, triethylenediamine and N-methylmorpholine; preferably at least one of pyridine, triethylamine and tetramethylethylenediamine, most preferably tetramethylethylenediamine; the amount of the basic medium to be used is 1 to 50 moles, preferably 1.05 to 20 moles, more preferably 1.2 to 10 moles, particularly 2.3 moles, relative to 1 mole of abamectin B2a (the same applies to the amounts mentioned below).

The amount of the protecting reagent, namely, the allyl chloroformate, may be 2 to 12 moles, preferably 2 to 6 moles, more preferably 2 to 3 moles, particularly 2.4 moles, based on 1 mole of abamectin B2 a.

Suitable reaction conditions include: the temperature may be from-30 ℃ to 30 ℃, preferably from-30 ℃ to 10 ℃, and the time may be from 1 to 10 hours, preferably from 1 to 2 hours.

In step B), the organic solvent is at least one selected from the group consisting of dichloromethane, n-hexane, benzene, toluene, chloroform, tetrachloromethane, petroleum ether, chlorobenzene, dioxane, methanol and tetrahydrofuran, preferably at least one selected from the group consisting of dichloromethane, trichloromethane and tetrahydrofuran, and most preferably dichloromethane; the amount of the organic solvent to be used may be 1 to 100L, preferably 2 to 10L, more preferably 3 to 5L, particularly 3.2L, relative to 1 mole of the compound represented by the formula (II).

Wherein the elimination reagent is at least one of acetic anhydride, trifluoroacetic anhydride, trifluoromethanesulfonic anhydride, methanesulfonyl chloride, p-toluenesulfonyl chloride and benzenesulfonyl chloride; preferably trifluoromethanesulfonic anhydride, methanesulfonyl chloride, most preferably trifluoromethanesulfonic anhydride; the elimination reagent may be used in an amount of 0.5 to 20 moles, preferably 1 to 10 moles, more preferably 1 to 5 moles, particularly 1.2 moles, based on 1 mole of the compound represented by the formula (II).

The organic base is selected from at least one of pyridine, triethylamine, ethylenediamine, tetramethylethylenediamine, triethylenediamine, N-methylmorpholine, tetramethylammonium hydroxide, potassium tert-butoxide, monoethanolamine and triethanolamine; preferably at least one selected from pyridine, triethylamine and tetramethylethylenediamine, most preferably pyridine. The organic base is used in an amount of 1 to 50 mol, preferably 1.05 to 20 mol, more preferably 1.2 to 10 mol, particularly 3.9 mol, based on 1 mol of the compound represented by the formula (II).

The elimination catalyst is at least one of DBU (1, 8-diazabicycloundec-7-ene), DMAP (4-dimethylaminopyridine), sodium sulfate, potassium sulfate and 4-methylpyridine, and is preferably selected from DBU and DMAP. The catalyst is used in an amount of 0.1 to 5 moles, preferably 0.1 to 2 moles, more preferably 0.1 to 1.5 moles, based on 1 mole of the compound represented by the formula (II).

Suitable reaction conditions include: the temperature may be from-50 ℃ to 40 ℃, preferably from-30 ℃ to 20 ℃, more preferably from-5 ℃ to-0 ℃; the time may be 1 to 10 hours, preferably 2 to 3 hours. The reaction is preferably carried out in an inert atmosphere, such as a nitrogen atmosphere.

In step C), the organic solvent is at least one selected from the group consisting of dichloromethane, n-hexane, benzene, toluene, chloroform, tetrachloromethane, petroleum ether, chlorobenzene, dioxane, methanol and tetrahydrofuran, preferably at least one selected from the group consisting of dichloromethane, trichloromethane and tetrahydrofuran, and most preferably dichloromethane; the amount of the organic solvent to be used may be 1 to 100L, preferably 2 to 10L, more preferably 3 to 5L, particularly 3.1L, relative to 1 mole of the compound represented by the formula (III).

The amount of the catalyst tetrakistriphenylphosphine palladium to be used may be 0.001 to 0.1 part by mass, preferably 0.005 to 0.03 part by mass, and more preferably 0.01 to 0.02 part by mass, based on 1 part by mass of the compound represented by the formula (III). The amount of sodium borohydride to be used is 0.001 to 0.1 part by mass, preferably 0.01 to 0.04 part by mass, and more preferably 0.02 to 0.03 part by mass, relative to 1 part by mass of the compound represented by the formula (III).

Suitable deprotection reaction conditions include: the temperature may be from-10 ℃ to 20 ℃, preferably from 0 ℃ to 5 ℃; the time may be 0.5 to 4 hours, preferably 1 to 2 hours.

In step D) of the above process, the organic solvent is at least one selected from the group consisting of dichloromethane, 1, 2-dichloroethane, isopropyl acetate, ethyl acetate, n-hexane, benzene, toluene, chloroform, tetrachloromethane, petroleum ether, chlorobenzene, dioxane and tetrahydrofuran, preferably at least one selected from the group consisting of dichloromethane, 1, 2-dichloroethane and isopropyl acetate, most preferably dichloromethane; the amount of the organic solvent to be used may be 1 to 100L, preferably 2 to 10L, more preferably 3 to 5L, particularly 3.1L, relative to 1 mole of the compound represented by the formula (Ia).

Wherein the alkaline medium is selected from at least one of pyridine, triethylamine, ethylenediamine, tetramethylethylenediamine, triethylenediamine and N-methylmorpholine; preferably selected from pyridine, triethylamine, tetramethylethylenediamine, most preferably tetramethylethylenediamine; the amount of the basic medium to be used is 1 to 10 mol, preferably 1.05 to 5 mol, more preferably 1.2 to 3 mol, particularly 2.3 mol, relative to 1 mol of the compound represented by the formula (Ia).

Wherein the amount of the protecting reagent, i.e., dilute propyl chloroformate, used is 1 to 8 moles, preferably 1 to 3 moles, more preferably 1 to 1.2 moles, particularly 1.17 moles, based on 1 mole of the compound represented by the formula (Ia).

Suitable reaction conditions include: the temperature can be-30 ℃ and the time is 0.5-24 hours.

In step E, the organic solvent is at least one selected from dichloromethane, n-hexane, benzene, toluene, chloroform, tetrachloromethane, petroleum ether, chlorobenzene, dioxane and tetrahydrofuran, preferably at least one selected from dichloromethane, chloroform and tetrahydrofuran, and most preferably dichloromethane; the amount of the organic solvent to be used may be 1 to 100L, preferably 2 to 10L, more preferably 3 to 5L, particularly 3.1L, relative to 1 mole of the compound represented by the formula (IV).

Wherein the alkali is selected from at least one of pyridine, triethylamine, ethylenediamine, tetramethylethylenediamine, triethylenediamine and N-methylmorpholine; preferably selected from pyridine, triethylamine, tetramethylethylenediamine, most preferably tetramethylethylenediamine; the amount of the base to be used is 1 to 10 mol, preferably 1.05 to 5 mol, more preferably 1.2 to 3 mol, particularly 2.3 mol, based on 1 mol of the compound represented by the formula (IV).

Wherein the amount of the oxidizing reagent dimethyl sulfoxide is 1 to 8 moles, preferably 2 to 5 moles, and more preferably 2.8 to 3 moles, based on 1 mole of the compound represented by the formula (IV); the amount of the phenyl dichlorophosphate to be used is 0.5 to 6mol, preferably 0.8 to 5 mol, more preferably 1 to 2 mol.

Suitable oxidation reaction conditions include: the temperature may be from-30 ℃ to 0 ℃, preferably from-20 ℃ to-10 ℃, and the time may be from 0.5 to 2 hours, preferably from 0.6 to 1 hour.

In step F), the organic solvent is at least one selected from the group consisting of dichloromethane, 1, 2-dichloroethane, isopropyl acetate, ethyl acetate, n-hexane, benzene, toluene, chloroform, tetrachloromethane, petroleum ether, chlorobenzene, dioxane and tetrahydrofuran, preferably at least one selected from the group consisting of dichloromethane, 1, 2-dichloroethane and isopropyl acetate, most preferably dichloromethane; the amount of the organic solvent to be used may be 1 to 100L, preferably 1 to 10L, more preferably 1 to 5L, and particularly 2.2L, relative to 1 mole of the compound represented by the formula (V).

Wherein the Lewis acid is selected from at least one of acetic acid, propionic acid, zinc trifluoroacetate, zinc chloride, zinc p-toluenesulfonate, boron trifluoride, aluminum chloride, ferric chloride and antimony pentafluoride, preferably at least one of acetic acid, zinc chloride and zinc trifluoroacetate, and most preferably acetic acid and/or zinc trifluoroacetate; the amount of the Lewis acid to be used is 0.01 to 10 mol, preferably 0.05 to 5 mol, more preferably 0.10 to 4 mol, relative to 1 mol of the compound represented by the formula (V); alkylamino (R)₁NH₂) The amount of (B) may be 1.5 to 50 mol, preferably 3-20 moles, more preferably 5-10 moles, in particular 9.2 moles; the reducing agent sodium borohydride is used in an amount of 0.001 to 0.5 parts by weight, preferably 0.005 to 0.3 parts by weight, and more preferably 0.01 to 0.02 parts by weight, relative to 1 part by weight of the compound represented by formula (V).

Suitable amination, reduction reaction conditions include: the temperature may be from-30 ℃ to 50 ℃, preferably from 5 ℃ to 25 ℃, more preferably from 10 ℃ to 15 ℃, and the time may be from 0.5 to 8 hours, preferably from 0.5 to 2 hours.

In step G), the organic solvent is at least one selected from dichloromethane, 1, 2-dichloroethane, methanol, isopropyl acetate, ethyl acetate, n-hexane, benzene, toluene, chloroform, tetrachloromethane, petroleum ether, chlorobenzene, dioxane and tetrahydrofuran, preferably at least one selected from dichloromethane, 1, 2-dichloroethane, methanol and isopropyl acetate, and most preferably a mixed solvent of dichloromethane and methanol, wherein the volume ratio of the two solvents may be 10: 1-1: 1, specifically 3: 1; the amount of the organic solvent to be used may be 1 to 100L, preferably 2 to 10L, more preferably 3 to 5L, and particularly 3.6L, per 1 mol of the compound represented by the formula (VI).

Wherein the amount of the catalyst tetrakis-triphenylphosphorated-palladium may be 0.001 to 0.1 part by mass, preferably 0.005 to 0.03 part by mass, more preferably 0.01 to 0.02 part by mass, relative to 1 part by mass of the compound represented by the formula (VI); the amount of sodium borohydride to be used is 0.001 to 0.1 part by mass, preferably 0.01 to 0.04 part by mass, and more preferably 0.02 to 0.03 part by mass.

Suitable deprotection reaction conditions include: the temperature may be from-10 ℃ to 20 ℃, preferably from 0 ℃ to 5 ℃, and the time may be from 0.5 to 4 hours, preferably from 1 to 2 hours.

In step H) of the above process, the organic solvent is at least one selected from the group consisting of dichloromethane, 1, 2-dichloroethane, isopropyl acetate, ethyl acetate, n-hexane, benzene, toluene, chloroform, tetrachloromethane, petroleum ether, chlorobenzene, dioxane and tetrahydrofuran, preferably at least one selected from the group consisting of dichloromethane, 1, 2-dichloroethane and isopropyl acetate, most preferably dichloromethane; the amount of the organic solvent to be used may be 1 to 100L, preferably 2 to 10L, more preferably 3 to 5L, and particularly 3.1L, relative to 1 mol of the compound represented by the formula (V).

Wherein the Lewis acid is selected from at least one of zinc trifluoroacetate, zinc chloride, zinc p-toluenesulfonate, boron trifluoride, aluminum chloride, ferric chloride and antimony pentafluoride, preferably at least one of zinc chloride, zinc p-toluenesulfonate and zinc trifluoroacetate, and most preferably zinc trifluoroacetate; the amount of the Lewis acid to be used is 0.01 to 10 moles, preferably 0.05 to 5 moles, more preferably 0.10 to 3 moles, based on 1 mole of the compound represented by the formula (V); the hexamethyldisilazane may be used in an amount of 1.5 to 50 moles, preferably 3 to 20 moles, more preferably 4.5 to 10 moles, and particularly 4.7 moles; the amount of the reducing agent sodium borohydride to be used is 0.001 to 0.5 parts by mass, preferably 0.005 to 0.4 parts by mass, more preferably 0.01 to 0.02 parts by mass, relative to 1 part by mass of the compound represented by the formula (V); the amount of the methanol is 0.5 to 5 parts by mass, preferably 1 to 3 parts by mass, and more preferably 1.5 to 2 parts by mass.

Suitable amination, reduction reaction conditions include: the temperature may be from 0 ℃ to 80 ℃, preferably from 5 ℃ to 70 ℃, and the time may be from 1 to 8 hours, preferably from 1 to 2 hours.

In step I), the organic solvent is at least one selected from dichloromethane, 1, 2-dichloroethane, methanol, isopropyl acetate, ethyl acetate, n-hexane, benzene, toluene, chloroform, tetrachloromethane, petroleum ether, chlorobenzene, dioxane and tetrahydrofuran, preferably at least one selected from dichloromethane, 1, 2-dichloroethane, methanol and isopropyl acetate, and most preferably a mixed solvent of dichloromethane and methanol, wherein the volume ratio of the two solvents may be 10: 1-1: 1, specifically 3: 1, the organic solvent may be used in an amount of 1 to 100L, preferably 2 to 10L, more preferably 3 to 5L, per 1 mol of the compound represented by the formula (VII).

Wherein the amount of the catalyst tetrakistriphenylphosphine palladium may be 0.001 to 0.1 part by mass, preferably 0.005 to 0.03 part by mass, more preferably 0.01 to 0.02 part by mass, relative to 1 part by mass of the compound represented by the formula (VII); the amount of sodium borohydride to be used is 0.001 to 0.1 part by mass, preferably 0.01 to 0.04 part by mass, and more preferably 0.02 to 0.03 part by mass.

In step J) of the above process, the organic solvent is at least one selected from the group consisting of dichloromethane, 1, 2-dichloroethane, isopropyl acetate, ethyl acetate, n-hexane, benzene, toluene, chloroform, tetrachloromethane, petroleum ether, chlorobenzene, dioxane and tetrahydrofuran, preferably at least one selected from the group consisting of dichloromethane, 1, 2-dichloroethane and isopropyl acetate, most preferably dichloromethane; the amount of the organic solvent to be used may be 1 to 100L, preferably 1 to 10L, more preferably 1 to 5L, particularly 1.8L, per 1 mol of the compound represented by the formula (VII).

Wherein the alkaline medium is selected from at least one of pyridine, triethylamine, ethylenediamine, tetramethylethylenediamine, triethylenediamine and N-methylmorpholine; preferably selected from pyridine, triethylamine, tetramethylethylenediamine, most preferably pyridine; the amount of the basic medium to be used is 0.1 to 10 mol, preferably 0.1 to 5 mol, more preferably 0.1 to 3 mol, relative to 1 mol of the compound represented by the formula (VII).

Wherein the amount of the acid anhydride or acid chloride as the acylating agent to be used is 0.1 to 8 mol, preferably 0.1 to 3 mol, more preferably 0.1 to 1.2 mol, based on 1 mol of the compound represented by the formula (VII).

Suitable acylation reaction conditions include: the temperature may be from-30 ℃ to 50 ℃, preferably from 0 ℃ to 30 ℃, and the time may be from 1 to 30 hours, preferably from 1 to 24 hours.

In the above process step K), the organic solvent is at least one selected from the group consisting of dichloromethane, 1, 2-dichloroethane, methanol, isopropyl acetate, ethyl acetate, n-hexane, benzene, toluene, chloroform, tetrachloromethane, petroleum ether, chlorobenzene, dioxane and tetrahydrofuran, preferably at least one selected from the group consisting of dichloromethane, 1, 2-dichloroethane, methanol and isopropyl acetate, and most preferably a mixed solvent of dichloromethane and methanol, and the volume ratio of the two solvents may be (10-1): 1, specifically 3: 1; the amount of the organic solvent to be used may be 1 to 100L, preferably 2 to 10L, more preferably 3 to 5L, and particularly 3.6L, relative to 1 mole of the compound represented by the formula (VIII).

Wherein the amount of the catalyst tetrakistriphenylphosphine palladium may be 0.001 to 0.1 part by mass, preferably 0.005 to 0.03 part by mass, more preferably 0.01 to 0.02 part by mass, relative to 1 part by mass of the compound represented by the formula (VIII); the amount of sodium borohydride to be used is 0.001 to 0.1 part by mass, preferably 0.01 to 0.04 part by mass, and more preferably 0.03 to 0.04 part by mass.

In the above salt-forming method, the salt-forming reagent may be used in an amount of 1 to 8 moles, preferably 1 to 3 moles, and more preferably 1 to 1.2 moles, based on 1 mole of the compound represented by the formula (ic).

In a further aspect, the compounds Ia of the invention are important intermediates for the preparation of insecticidal, acaricidal and nematicidal compounds, and as a novel compound are one of the objects of the invention.

In the field of pest control, salt-forming products of the compounds Ia, Ib, ic, Id and Ib, ic show good active ingredients, show high prevention or treatment activity in insect killing, mite killing, nematode killing and the like, and have the characteristics of high activity, wide insecticidal spectrum, no drug resistance, safety, long residual effect period and the like.

Within the scope of the subject matter of the present invention it is possible with the compounds according to the invention to successfully control pests, in particular from the orders lepidoptera, coleoptera, orthoptera, isoptera, psocoptera, pediculosis, mallophaga, thysanoptera, heteroptera, hemiptera (e.g. aphids), hymenoptera, diptera, siphonaptera, thysanoptera and acarina, in particular from the orders acarina, diptera, thysanoptera, lepidoptera and coleoptera.

The following pests can be particularly well controlled:

the plant may be selected from the group consisting of Spodoptera, Trichoplusia (e.g., Dermatophagoides pteronyssinus), Onychii (e.g., Trichophyton fuliginosus), Onychii (e.g., Hedychium falcata), Onychii (e.g., Hedychium falcatum), Plutella, Echinococcus, Endoptera, Spodoptera, Echinoderma (e.g., Spodoptera exigua), Echinoderma (e.g., Ceripomoea stegia punctata), Aedes aegypti, Diptera, Spodoptera, Echinocactus, Trichoplusia, Spodoptera, Tussah, anthurium, gossypus, drynaria, spodoptera, pholiota, gecko, schoenopsis, photophoronella, aphididae, aphid, prodenia, plutella, curculigo, anthoid, cochlearia, eucheuma, aleurites, silvermoth, silverleaf noctuid, striped cochlearia, banded looper, bridgemaking, pelagia, venezuelaria, predatory beetle, beet cryptogam, chervil, cutworm, arachnida, prodenia, deadlocks, cutworm, spiraea, pinocembria, date tip moth, sprouted bud wheat moth, leaf-piercing moth, meadow-bug, sweetpotato whitefly, aleyrodid, black-haired black-feather, cockchaetaria, aleyrodidymis, lash, spiraelia, spica, spodoptera, salpingia, codling moth, spodoptera, codonta, gelidium, byttella, byssus, byttva, byssus, the genera Heliothis, Hyphantria, Caryoptera, Hypocrea, Aphantria, Hypocrea, Richyriopsis, Red head Rickett, Diplophora, Plutella, Helicoverpa, Athetis, Graphoma, Carposina, peach fruit moth, Pieris, Brucella, Lysimachia, Mega, Heliothis, Solomonas, Cereus, Diospora, Phyllostachys, Phyllopsis, Phyllanthus, Phyllostachys, Aphis, Hypocladica, Hypocrea, Arctia, Orthosiphon, Glyphyllus, Gloeostera, Gloeostephia, Gloeostera, cnaphalocrocis, nephelandina, codling, looper, colestigmatis, pyropheuma, garcinia, spodoptera, crinis, ichthyophis, ostrinia, crinis, noctuid, cicada, crinopsis, codling moth, luria, ostrinia, crinopsis, ostrinia, cochlearia, Ctenore, Ctenocephalanoplos, ophiocladia, pelliota, cochinella, cochinchina, codling, cocklebur, codling, cocklebur, codling, armyworm, and armyworm, The plant is selected from the group consisting of Dioryza punctiferalis, Coprinus, Sudan Heliothis, Trichophyton, Ceriporiopsis, Cochinoma latum, Sclerotis, Dermatophagoides, Siphonostegia, Drosophila melanogaster, Ceratoptera, Dermatophagoides, Dactylis, Ceratoptera, Oplophora, Aphis, Spodoptera, Acronychia, Epilotus, Epinephelus, Ceripomoelletia, Spodoptera, Acronychia, Aphis, Acronychia, Aphis, Achyrea, Acronychia, Aphis, Achyrea, Achna, Aphis, Achnophora, Adenophora, Aphis, Adenophora, Aphis, trichoplusia, Phlebia, Diplophagoides, Hypocrea, Trichoplusia, Xanthoceratis, Ophiophaga, Dictyocaulus, Trichoplusia, Entomophthorimaea, Achillea, Oridophysa, Amaranthus, Echinocapsa, Heliothis, Noctus, Echinocapsa, Heliothis, Echinocapsa, Echinocactus, Echinococcus, Juglans, Gamopsis, Helicoverpa, Giardia, Gimera, Glyphyllus, Onyura, Selaginella, Arctia, Trichopsis, Trichoplusia, Grapholitha, Graptomeria, Graptopetunia, Graptopetechia, Achillea, Heliothis, Grapholitsea, Grapholitha, and Haemaria, Popula, Cocoilia, Codonnax, Codonaea, and Adenophora, Spodoptera, diaphania, trichina, trichlorphon, amphiregulus, spodoptera, prodenia, spica, noctuid, codling moth, diad moth, cochinella, cochineal moth, tortricid, carpesia, venezuelan, tortricid, hyalothin, sabdaria, aluciella, alucina, nigella, plutella, gelsemiaquilaria, gelsemium, piniper, gelechiid, gelsemium, crinis, lepigone, pholiota, codling moth, tarsiella, prodenia, plutella, codling moth, salmonella, lepigone, codling moth, lycopodium, plutella, liptera, eupatorium, codling moth, tarda, codling moth, leptospora, codling moth, aleyrodidymphaea, aleyrodidymotreta, limnopsis, limnophora, limnoperna, limnopsis, meadowella, meadowfoam, Taiwan chlamydomonas, noctuid, white-fin Phlebia, Periplaneta, Madela, leaf miner, Spanish, Philadelphia, Phlebia, rustic Spodoptera, leaf miner, Alternaria, Ophiopogon, Spodoptera, locusta, Pleuroptera, noctuid, Convolvulus, Chlorophyta, Pothida, Spodoptera, Agileria, Goniotella, Armoutis, mothfly, Heliothis, Aphis, Cnaphalocrocis, Phlebopus, cabbage looper, Heliothis, Helicoverpa, Phlebia, Leptoporis, Diabrotica, Acronychia, Spodoptera, Spodopterothria, Heliothis, Helicoverpa, Hel, The plant is selected from the group consisting of Spodoptera, Coprinus, Pectinophis, Musca, Ostrinia, Phlebopus, Heliothis, Hyphoma, Hypocrea, Neosporotrichum, Scedosporidium, SeD, Ornithogalum, Phaliota, Neuropilea, Heliothis, Farforma, Heliothis, Spodoptera, Arctia, Bombycis, Spodoptera, Trichoplusia, Spodoptera, Platya, Trichoplusia, Spodoptera, Geophila, Spodoptera, Heliothis, Helicoverpa, Gelatinospora, Geophila, Setaria, Ostrinia, the genus Euglena, Panonychus, Drosophila, Trichoplusia, Periploca, Phlebia, Heliothis, Philippine, Spodoptera, Ceriporiopsis, Phlebia, Philippine, Ceriporia, Orodiella, Periplaneta, Pantoea, Ceriporia, Proteus, Tricolopsis, Philippine Phlebia, Philippine grass, Drosophila, Aristolochia, Purpura, Pseudoplutella, Philippine moth, crinopilea, Rhynchopogyrus, Physalis, Pleuroptera, Heliothis citri, Physalis, Spodopterogynonella, Pieris, Helicoverpa, Physalis, Helicoverpa, Heliothis, Helicoverpa, Phytophaga, Helicoverpa, Hel, Aspongopus, Tariff tarda, Tariff spider mite, Nepalea, codling moth, striped rice borer, Dipper, Polaris, Aognathus, Wood moth, Ripodophyllum, armyworm, Dryopteris, Lepidium, Primordia, Philippine flea, Alopecurtis, scale, Acremoculum, Philippine moth, Phlebia, Philanthia, Naemophilus, Nepholidium, Neofilicinia, Achyrdinia, Achyridophysalis, Acidophysalis, Acremotifera, Trichoplusia, Spodoptera, Spodopterocarpus, Aphis, Phaleria, Achyriopsis, Acremotifera, Acremotifloranthus, Acremotifera, Spodoptera, Acremotifera, Acremotifolia, Acremova, Acremotifer, Acremova, Spodoptera, Acremova, Acremotifer, Acremo, Ailanthus, cicada, sarcoptica, spinetora, Trichoplusia, Tortoise, Ohiophaga, Selaginella, Diploptera, Diptera, Arctia, Occidomycidae, Selaginella, Scirpus, Aphanizomorpha, Diplocereus, Orthosiphon, Heliothis, Tabanus, Heliothis, Periploca, Oligomorpha, Spodoptera, Aristolochia, Heliothis, Ceratoptera, Heliothis, Helicoverpa, Heliothis, Helicoverpa, Heliothis, Helicoverpa, Trichosporon, Pond cicada, Tarsonemus, Trichoplusia, thrips (e.g., thrips palmae, thrips tabacis), Tylophora, Ceramia, Trichoplusia, Aedes, Glyphylla, Trichoplusia, Phlebia, Tripteris, Pseudobagrus, Cochastis, Trichoplusia, Ophiopogon, Pediculus, Pectinatus, Globus, Trichoplusia, Geckia, Trichoplusia, Leptoporis, Geranium, Pieris, Coptochlearia, Trichoplusia, Trichophyton, Phoma, Trichophyton, genus Toxoplasma, genus Diptera, genus Leptochlamys, genus Mylophaga.

It is also within the scope of the inventive subject matter to use the compounds of the present invention to control acarid pests. The mites include: tetranychus cinnabarinus, goiter, tetranychus urticae, rhynchophorus, physcion, tetranychus urticae, merseiulus merdae, cancer crab, hemiscabies, giant beard mites, varroa, carnivorous, downy mites, red mites, etc.,

it is also within the scope of the inventive subject matter to use the compounds of the present invention to control nematoda pests. The pests include: such as Meloidogyne spp, cyst nematode, stem nematode, leaf nematode, and the like;

in particular cyst nematodes, such as beet cyst nematodes; heterodera species, such as, for example, anoectochilus tuberosus; meloidogyne species such as Meloidogyne incognita, Meloidogyne javanica and Heterodera species such as Heterodera glycines; perforatole nematodes, such as the analogous perforatole nematodes; pratylenchus species, such as Pratylenchus negectans (Pratylenchus negectans) and Pratylenchus penetrans; the genus Microtylenchus, such as hemitylenchus penetrans; longneedle nematodes, Bursaphelenchus, Ostertagia, Apheenchoides, and Anguilla.

The compounds according to the invention are useful for controlling, i.e. inhibiting and/or destroying, pests which occur on plants, in particular on useful plants and ornamentals in agriculture, horticulture and forestry, or pests of the aforementioned type which occur on parts of the plants, such as fruits, flowers, leaves, stems, tubers or roots. After the use of the compounds according to the invention, plant parts which grow later can sometimes also be protected from attack by those pests.

Target crops include in particular cereals, such as wheat, barley, rye, oats, rice, maize and sorghum; beets, such as sugar beet and fodder beet; fruits such as pomes, stone fruits, stone-free small fruits and citrus fruits, such as apples, pears, plums, peaches, apricots, oranges, lemons, grapefruits and chinese citrus, cherries and berries, such as strawberries, raspberries and blackberries; leguminous plants, such as beans, lentils, peas and soybeans; oil plants, such as rape, mustard, poppy, olive, sunflower, coconut, sesame oil, cocoa and groundnut; cucurbitaceae, such as cucurbits, cucumbers and melons; fiber plants, such as cotton, flax, hemp and jute; vegetables such as spinach, endive, asparagus, cabbages, carrots, onions, tomatoes, potatoes and peppers; lauraceae, such as avocado, cinnamon and camphor; and tobacco, nuts, coffee, eggplant, sugar cane, tea, pepper, grapes, hops, bananas, natural rubber plants and ornamental plants.

The invention also relates to a pesticide composition containing at least one compound according to the invention.

The pesticide composition comprises an abamectin B2a high-alkene derivative (a compound shown in a formula I) and an agriculturally acceptable carrier.

The avermectin B2a high-alkene derivative can be a single compound or a mixture of several compounds.

The pesticidal composition can be prepared into any formulation acceptable in agro-pharmacology, such as emulsifiable concentrates, suspension concentrates, directly sprayable or dilutable solutions, coatable pastes, dilute emulsions, wettable powders, soluble powders, dispersible powders, wettable powders, dusts, granules and encapsulation of polymers, and the specific formulation can be selected according to the intended target and environment.

The active ingredients are used in those compositions in pure form, for example as solid active ingredients of a particular particle size, or preferably together with at least one of the customary auxiliaries in formulation technology, such as extenders, for example, solvents or solid carriers, or surface-active compounds (surfactants), it being possible only to use physiologically tolerable additives in the field of parasite control in humans, domestic animals, productive livestock and pets.

Suitable solvents are: aromatic hydrocarbons, preferably hydrocarbons containing from 8 to 12 carbon atoms, such as mixed xylenes or substituted naphthalenes; aliphatic or cycloaliphatic hydrocarbons, such as paraffins or cyclohexane; ketones, such as cyclohexanone, isophorone or diacetone alcohol; alcohols, such as ethanol, propanol or butanol; glycols and their acyl and esters, such as propylene glycol, dipropylene glycol, ethylene glycol or ethylene glycol monoformyl or monoethyl ether; strongly polar solvents such as N-methylpyrrolidin-2-one, dimethyl sulfoxide or N, N-dimethylformamide, water, non-epoxidized or epoxidized vegetable oils, such as non-epoxidized or epoxidized rapeseed oil, castor oil, coconut oil or soybean oil, and silicone oils.

Solid carriers for e.g. dusts and dispersible powders are usually calcite, talc, kaolin, montmorillonite, attapulgite, silicic acid, pumice, broken brick, sepiolite, bentonite, dolomite, plant residue powders.

Depending on the nature of the active compounds to be formulated, the surface-active compounds are nonionic, cationic and/or anionic surfactants or surfactant mixtures having good emulsifying, dispersing and wetting properties. The following list of surfactants is considered as an example only; many other surfactants which are conventional in formulation technology and which are suitable according to the invention are described in the relevant literature.

Nonionic surfactants are, in particular, lipononylphenol-polyethoxyethanol, castor oil polyglycol ethers, polyoxypropylene-polyoxyethylene adducts, tributylphenoxypolyethoxyethanol, polyethylene glycol, octylphenoxypolyethoxyethanol, polyoxyethylene sorbitan trioleate.

Cationic surfactants are in particular quaternary ammonium salts which contain as substituents at least one alkyl radical having from 8 to 22 carbon atoms and as further substituents a lower non-halogenated or halogenated alkyl, benzyl or lower hydroxyalkyl radical. The salts are preferably in the form of halides, methylsulfates or ethylsulfates. Examples are stearyl-trimethyl-amine chloride and benzyl-bis- (2-chloroethyl) -ethyl-ammonium bromide.

Suitable anionic surfactants may be water-soluble soaps and water-soluble synthetic surface-active compounds. Suitable soaps are the sodium or potassium salts of oleic or stearic acid, or of naturally occurring fatty acid mixtures, as may be obtained, for example, from coconut oil or tall oil; in addition, fatty acid methyl-taurates are also present. However, more often synthetic surfactants are used, in particular fatty sulfonates, fatty sulfates, sulfonated benzimidazole derivatives or alkylaryl sulfonates. Fatty acid sulfonates and sulfates are typically in the form of alkali metal salts, alkaline earth metal salts, or substituted or unsubstituted ammonium salts, typically having alkyl groups of from 8 to 22 carbon atoms, which also include the alkyl portion of the acyl group; examples are the sodium or calcium salts of lignosulfonic acid, of dodecylsulfonic acid ester, or of fatty alcohol sulfate mixtures prepared from natural fatty acids. Also included are sulfate ester salts and sulfonate salts of fatty alcohol-ethylene oxide adducts. The sulfonated benzimidazole derivative preferably contains 2 sulfonic acid groups and a fatty acid group having 8 to 22 carbon atoms. The alkylaryl sulfonates are, for example, the sodium, calcium or triethanolammonium salts of dodecylbenzenesulfonic acid, of dibutylphthalansulfonic acid or of naphthalenesulfonic acid-formaldehyde condensates.

Agrochemical formulations generally contain from 0.1 to 99%, preferably from 0.1 to 95%, of active compound; the content of solid or liquid auxiliaries (excluding surfactants) is from 1 to 99.9%, preferably from 5 to 99.9%; the content of the surfactant is 0-25%, preferably 0.1-20%; while concentrated compositions are more preferred as commercial products, end users typically use dilute compositions containing relatively low concentrations of the active compound. Preferred compositions have in particular the following composition (% by weight):

and (3) missible oil:

active ingredients: 1-90%, preferably 5-20%;

surfactant (b): 1-30%, preferably 10-20%;

solvent: 5-98%, preferably 70-85%.

Solution preparation:

powder preparation:

active ingredients: 0.1 to 10%, preferably 0.1 to 1%;

solid carrier: 99.9 to 90%, preferably 99.9 to 99%.

Suspension concentrate:

active ingredients: 5-75%, preferably 10-50%;

water: 94-24%, preferably 88-30%;

surfactant (b): 1-40%, preferably 2-30%.

Wettable powder:

active ingredients: 0.5-90%, preferably 25-80%;

surfactant (b): 0.5-20%, preferably 1-15%;

solid carrier: 5-99%, preferably 15-98%.

Granules:

active ingredients: 0.5-30%, preferably 5-20%;

solid carrier: 99.5 to 70%, preferably 95 to 80%.

The compositions of the invention may also contain other solid or liquid auxiliaries, such as stabilizers, for example vegetable or epoxidized vegetable oils (for example epoxidized coconut, rapeseed or soybean oil), defoamers, for example silicone oils, preservatives, viscosity regulators, adhesives and/or tackifiers, and also fertilizers or other active ingredients for achieving specific effects, for example acaricides, bactericides, fungicides, nematicides, molluscicides or selective herbicides.

The pesticidal compositions according to the invention are prepared in a known manner, in the absence of adjuvants, for example by grinding, sieving and/or extruding the solid active ingredient or the mixture of active ingredients to, for example, a certain particle size, and in the presence of at least one adjuvant, for example by first mixing and/or grinding the active ingredient or the mixture of active ingredients with the adjuvant. The invention also relates to a process for preparing the compositions according to the invention and to the use of the compounds of formula (I) for preparing these compositions.

The invention also relates to a method for using the above-mentioned pesticidal composition, i.e. for controlling pests of the above-mentioned type, such as spraying, atomizing, dusting, coating, dressing, broadcasting or pouring, said method being chosen according to the intended target and the prevailing circumstances, and typically being used in a concentration of 0.l to 1000ppm, preferably 0.1 to 500ppm, of active ingredient. The amount per hectare is generally from l to 2000g of active ingredient per hectare, in particular from 10 to 1000g, preferably from 20 to 600 g; more preferably 20-100 g/ha.

In the field of crop protection, the preferred method of application is to apply to the foliage of the plants (foliar application), the number and amount of applications depending on the risk of infestation by the pests in question. However, when the locus of the plant is impregnated with a liquid formulation or when the active ingredient is incorporated in solid form, for example in particulate form, into the plant locus, for example soil (soil application), the active ingredient can also enter the plant through the roots (systemic action). In the case of rice crops, the granules can be applied in metered amounts to a paddy field under irrigation.

The crop protection products of the invention are also suitable for protecting plant propagation material, for example seeds, such as fruits, tubers or cereals, or plant cuttings, from attack by animal pests. The propagation material may be treated with the composition prior to planting; for example, the seeds may be dressed prior to sowing. The active ingredients of the invention can also be applied to the cereals (coating) by impregnating the seeds with liquid preparations or coating them with solid preparations. The composition may also be applied to the planting site at the time of planting the propagation material, for example to a seed furrow during sowing. The invention also relates to a method of treatment of the plant propagation material and to plant propagation material so treated, thereby imparting pest resistance to such material.

In addition, the compound shown in the formula I and the application of the composition containing the compound shown in the formula I in controlling the pests of the types are also within the protection scope of the invention.

The invention focuses on the synthesis and activity screening of the derivative compound of B2a, develops the comprehensive utilization research work of abamectin B2, sequentially designs and synthesizes a plurality of series of B2a derivatives with brand new structures, and performs wide insecticidal activity determination on the target compound. The invention discloses compounds which are derived and synthesized from B2 and have brand new structures, olefinic bonds are arranged between 2, 3-positions and 23, 24-positions, and 4' -positions are amino or methylamino, and the compounds have high-efficiency insecticidal activity on multiple targets.

Drawings

FIG. 1 is a reaction scheme of step A of a process for the synthesis of a compound of formula (I).

FIG. 2 is a reaction scheme of step B of the process for the synthesis of the compound of formula (I).

FIG. 3 is a reaction scheme of step C of the process for the synthesis of the compound of formula (I).

FIG. 4 is a reaction scheme of step D of the process for the synthesis of the compound of formula (I).

FIG. 5 is a reaction scheme of step E of the process for the synthesis of the compound of formula (I).

FIG. 6 is a reaction scheme of step F of the process for the synthesis of the compound of formula (I).

FIG. 7 is a reaction scheme of step G of a process for the synthesis of compounds of formula (I).

FIG. 8 is a reaction scheme of step H of a process for the synthesis of compounds of formula (I).

FIG. 9 is a reaction scheme of step I of a process for the synthesis of compounds of formula (I).

FIG. 10 is a reaction scheme of step J of a process for the synthesis of compounds of formula (I).

FIG. 11 is a reaction scheme of step K in a process for the synthesis of compounds of formula (I).

FIG. 12 is a NMR spectrum of a compound of formula V prepared in example 1.5 of the present invention.

FIG. 13 is a NMR carbon spectrum of a compound of formula V prepared in example 1.5 of the present invention.

FIG. 14 shows the NMR spectrum of a compound of formula Ia, prepared according to example 1.3 of the present invention.

FIG. 15 is a NMR carbon spectrum of a compound of formula Ia, prepared according to example 1.3 of the present invention.

FIG. 16 is a chart of the formula ic (R) prepared in example 1.7 of the present invention₁Is CH₃) Nuclear magnetic resonance hydrogen spectrum of the compound.

FIG. 17 is a chart of the formula ic (R) prepared in example 1.7 of the present invention₁Is CH₃) Nuclear magnetic resonance carbon spectrum of the compound.

FIG. 18 is a NMR spectrum of Ic benzoate prepared in example 1.12 of the present invention.

FIG. 19 is a NMR carbon spectrum of Ic benzoate prepared in example 1.12 of the present invention.

FIG. 20 is a single crystal structural drawing of the Ic benzoate prepared in example 1.12 of this invention (identifying the 2, 3-olefinic bond position).

FIG. 21 is a single crystal structural drawing of the Ic benzoate prepared in example 1.12 of this invention (determination of the 23, 24-ethylenic position).

Detailed Description

The present invention is described below with reference to specific embodiments, but the present invention is not limited thereto, and any modification, equivalent replacement, and improvement made within the spirit and principle of the present invention should be included in the scope of the present invention.

The experimental procedures used in the following examples are all conventional procedures unless otherwise specified.

Materials, reagents and the like used in the following examples are commercially available unless otherwise specified.

In the quantitative tests in the following examples, three replicates were set up and the results averaged.

1, synthesis of the compound of formula (i):

example 1.14 ", preparation of 5-allylavermectin B2a (formula II)

Adding 100g (0.112 mol) of abamectin B2a and 400mL of anhydrous dichloromethane into a 1000mL three-necked bottle, fully dissolving, cooling to-15 ℃, adding 30g (0.258 mol) of tetramethyl ethylenediamine, cooling to-20 ℃, slowly dropwise adding a mixed solution of 32g (0.265 mol) of dilute propyl chloroformate and 50mL of anhydrous dichloromethane, dropwise adding after 1 hour, reacting for 1 hour at-20 ℃, washing an organic phase with dilute hydrochloric acid after the reaction is finished, extracting dichloromethane, drying with anhydrous sodium sulfate, concentrating, and passing through a column to obtain 116g of a product II with the yield of 98%.

The structure validation data is as follows:¹H NMR(300MHz,CDCl₃)；δ5.68～6.06(m,5H,H9,H10,H11,CH₂＝CH-CH₂O),5.53～5.65(m,1H,H3),5.24～5.46(m,7H,H5,H1″,H19,CH₂＝CH-CH₂O),4.91～5.06(m,1H,H15),4.57～4.86(m,7H,H1′,H8ax2,CH₂＝CH-CH₂O),4.14(d,J＝6.1Hz,1H,H13),3.71～4.03(m,6H,7-OH,H23,23-OH,H5″,H5′,H6),3.41～3.71(m,10H,H25,H17,H3″,H3′,3″-OCH₃,3′-OCH₃),3.36～3.42(m,1H,H2),3.26(m,2H,H4′,H4”),2.48～2.79(m,2H,H12,H24),2.18～2.43(m,6H,H16x2,H2′,H2″),1.76～2.10(m,7H,H18,Me4a,H20),1.45～1.69(m,8H,Me14a,H26,H27x2,H22x2),1.24～1.35(m,6H,Me6′,Me6″),1.19(d,J＝6.9Hz,3H,Me12a),0.86～1.03(m,9H,H28,Me24a,Me26a)；¹³C NMR(75MHz,CDCl₃)δ172.89,154.47,154.35,139.03,137.61,135.30,132.78,131.17,124.43,121.15,120.07,118.41,118.35,117.23,99.30,97.81,94.47,81.33,80.56,80.30,80.15,78.94,76.93,76.30,75.23,73.18,70.47,69.51,68.38,68.21,68.08,67.41,66.79,65.85,56.69,56.11,45.38,40.85,40.41,39.39,36.07,35.38,34.79,34.70,34.15,33.79,29.32,26.93,19.86,19.29,18.01,16.97,14.80,13.43,12.09,11.46.HRMS:calcd for C₅₆H₈₂O₁₉(M+H)⁺:1059.5529；found,1059.5534.

example 1.24 ", preparation of 5-allyloxycarbonylalmectin B2a higher alkene derivative Compound (formula III)

118g (0.112 mol) of the substance shown in the formula (II) is dissolved in 350mL of anhydrous dichloromethane, 35 g (0.442 mol) of pyridine is added, after the solution is fully dissolved, nitrogen is protected, the temperature is reduced to-5 ℃, 36.6g (0.130 mol) of trifluoromethanesulfonic anhydride is added, the solution is dripped off after 0.5 hour, the reaction is carried out for 2 hours at-5 ℃, 7.61g of elimination catalyst DBU (1, 8-diazabicycloundecen-7-ene, 0.05 mol) is added, the temperature is gradually increased to room temperature, the reaction is continued for 3 hours, and the reaction is monitored to be complete by liquid chromatography. After the reaction, the organic phase was washed with dilute hydrochloric acid, extracted with dichloromethane, dried over anhydrous sodium sulfate, and then dichloromethane was distilled off, and the product represented by formula (iii) was obtained by column chromatography purification in a yield of 90%.

The structure validation data is as follows:¹H NMR(300MHz,CDCl₃)δ5.96–5.72(m,6H,H3,H9,H10,H11,CH₂＝CH-CH₂O),5.51–5.37(m,9H,H1”,H23,H4’,H 4”,H19,CH₂＝CH-CH₂O),5.01(s,1H,H15),4.86–4.66(m,7H,H1’,7-OH,H6,CH₂＝CH-CH₂O),4.33(d,J＝6.4Hz,1H,H13),4.11–3.53(m,11H,H4,20-CH₂,H3’,H3”,H5’,H5”,8-CH₂,22-CH₂),3.50–3.38(m,8H,H17,H25,3’-OCH₃,3”-OCH₃),3.35–3.21(m,2H,18-CH₂),2.19(m,J＝9.7Hz,6H,16-CH₂,2’-CH₂,2”-CH₂),1.77–1.44(m,14H,H12,Me24a,Me14a,Me4a,H26,27-CH₂),1.28(d,J＝6.4Hz,6H,6’-Me,6”-Me),1.19(d,J＝7.0Hz,3H,28-Me),1.00(t,J＝7.4Hz,3H,Me12a),0.80(d,J＝6.7Hz,3H,Me26a).¹³CNMR(75MHz,CDCl₃)δ173.20,154.44,154.25,138.94,137.74,134.73,132.94,131.17,124.41,121.19,120.10,118.42,117.86,117.09,99.35,97.83,94.28,81.18,80.69,80.30,80.05,79.01,76.88,76.30,75.25,73.22,70.51,69.53,68.40,68.21,68.09,67.52,66.75,65.86,56.72,56.20,45.43,40.90,40.42,39.39,36.21,35.80,34.80,34.72,34.11,33.84,29.35,26.36,19.95,19.31,18.04,16.99,14.87,13.42,12.21,11.65.HRMS:calcd for C₅₆H₈₀O₁₈(M+H)+:1041.5417；found,1041.5415.

example 1.34 preparation of a Highene derivative Compound of hydroxyavermectin B2a (formula Ia)

Dissolving 116g (0.112 mol) of the substance shown in the formula (III) in 350mL of anhydrous dichloromethane, fully dissolving, cooling to 0 ℃, adding 1.16g (0.01 weight part) of tetrakis-triphenylphosphine palladium, adding 2.32g (0.02 weight part) of sodium borohydride, reacting at 0 ℃ for 1 hour, washing an organic phase with dilute hydrochloric acid after the reaction is finished, extracting with dichloromethane, drying with anhydrous sodium sulfate, concentrating, and passing through a column to obtain 94g of a product Ia, wherein the final yield is 96%.

The structure validation data is as follows:¹H NMR(300MHz,CDCl₃)δ5.74(dd,3H,H9,H10,H11),5.49–5.35(m,4H,H15,H23,4”-OH,H19),5.04–4.92(m,1H,5-OH),4.79(d,1H,7-OH),4.68(m,2H,H1’,H1”),4.34–4.25(m,1H,H5),4.19–4.07(m,1H,H3),3.96(t,3H,H4,20-CH₂),3.87–3.45(m,7H,H3’,H3”,H13,H5’,H5”CH₂),3.43(d,6H,3’-OCH₃,3”-OCH₃),3.31–3.09(m,3H,H4”,18-CH₂),2.61–2.45(m,2H,H17,H4’),2.31(dd,3H,H25,16-CH₂),2.05(m,4H,2’-CH₂,2”CH₂),1.88–1.46(m,16H,H6,H12,Me24a,Me14a,Me4a,H26,22-CH₂,27-CH₂),1.27(t,6H,6’-Me,6”-Me),1.16(d,3H,28-Me),0.96(t,3H,Me12a),0.77(d,3H,Me26a)；¹³C NMR(75MHz,CDCl₃)；δ173.50,139.28,137.79,137.68,134.74,133.07,124.38,120.11,117.86,117.69,117.08,98.17,96.35,94.31,81.22,80.12,80.06,79.05,78.77,77.86,76.88,75.77,73.19,68.14,68.06,67.98,67.78,67.39,66.89,56.21,56.05,45.41,40.23,39.41,36.50,35.80,35.21,34.30,33.86,26.36,19.93,19.63,18.79,18.08,17.34,14.86,12.21,11.65.HRMS:calcd for C₄₈H₇₂O₁₄(M+H)⁺:873.4995；found,873.4997.

EXAMPLE 1.45 preparation of Alcomectin B2a allyl carbonyl derivative Compound (formula IV)

Dissolving 98g (0.112 mol) of a substance shown in a formula (Ia) in 350mL of anhydrous dichloromethane, fully dissolving, cooling to-15 ℃ after fully dissolving, adding 30g (0.258 mol) of tetramethyl ethylenediamine, cooling to-20 ℃, slowly dropwise adding a mixed solution of 16g (0.132 mol) of dilute propyl chloroformate and 50mL of anhydrous dichloromethane, dropwise adding after 0.5 hour, reacting at-20 ℃ for 1 hour, washing an organic phase with dilute hydrochloric acid after the reaction is finished, extracting dichloromethane, drying with anhydrous sodium sulfate, concentrating, and passing through a column to obtain 104g of a product IV, wherein the final yield is 97%.

The structure validation data is as follows:¹H NMR(300MHz,CDCl₃)δ6.03–5.90(m,1H,CH₂＝CH-CH₂-O),5.88–5.68(m,3H,H9,H10,H11),5.67–5.16(m,8H,H15,H23,4”-OH,H19,H5,CH₂＝CH-CH₂-O,H1’),4.98(d,1H,H1”),4.79(d,1H,7-OH),4.65(dt,4H,H5’,H5”,CH₂＝CH-CH₂-O),4.18–4.01(m,2H,H3,H4),3.99–3.52(m,7H,H3’,H3”,H13,20-CH₂,CH₂),3.42(d,6H,3’-OCH₃,3”-OCH₃),3.39–3.35(m,1H,H4”),3.31–3.11(m,2H,18-CH₂),2.54(dd,2H,H17,H4’),2.37–2.01(m,7H,H25,16-CH₂,2’-CH₂,2”CH₂),1.60(dd,16H,H6,H12,Me24a,Me14a,Me4a,H26,,22-CH₂,27-CH₂),1.26(t,6H,6’-Me,6”-Me),1.16(d,3H,28-Me),0.96(t,3H,Me12a),0.76(d,3H,Me26a)；¹³C NMR(75MHz,CDCl₃)δ173.15,154.50,138.92,137.77,134.76,133.04,132.78,131.17,124.39,121.22,120.12,118.36,117.85,117.10,98.17,96.35,94.29,81.18,80.56,80.11,79.06,77.87,76.90,76.27,75.77,73.23,73.18,68.39,68.23,68.13,67.99,67.78,66.88,56.20,56.06,45.43,40.22,39.38,36.43,35.80,35.20,34.29,33.88,26.35,19.94,19.30,18.78,18.07,17.34,14.86,12.20,11.65.HRMS:calcdfor C₅₂H₇₆O₁₆(M+H)⁺:957.5206；found,957.5222.

EXAMPLE 1 preparation of 55-allyloxycarbonyl-4 "-carbonyl Avermectin B2a higher ene derivative Compound (V)

Dissolving 107g (0.112 mol) of the substance shown in the formula (IV) in 350mL of anhydrous dichloromethane, fully dissolving, cooling to-20 ℃, adding 30g (0.258 mol) of tetramethylethylenediamine, adding 25g (0.320 mol) of dimethyl sulfoxide, dropwise adding 50mL of dichloromethane solution of 25g (0.118 mol) of phenyl dichlorophosphate, continuing to react for 1 hour at-20 ℃, washing an organic phase with dilute hydrochloric acid after the completion of the reaction, extracting dichloromethane, drying with anhydrous sodium sulfate, and concentrating to pass through a column to obtain 99g of a product V with the yield of 93 percent.

The structure validation data is as follows:¹H NMR(300MHz,CDCl₃)δ5.93(s,1H,CH₂＝CH-CH₂-O),5.73(dd,3H,H9,H10,H11),5.55(d,2H,H15,H23),5.38(ddd,4H,H19,H5,CH₂＝CH-CH₂-O),5.26(dd,1H,H1’),4.99(d,1H,H1”),4.81(d,1H,7-OH),4.65(dt,4H,H5’,H5”,CH₂＝CH-CH₂-O),4.41(d,1H,H5),4.19(d,2H,H3,H4),4.06(dd,7H,H3’,H3”,H13,20-CH₂,CH₂),3.47(d,6H,3’-OCH₃,3”-OCH₃),3.35(dd,2H,18-CH₂),2.63–2.40(m,2H,H17,H4’),2.30(d,3H,H25,16-CH₂),2.08(d,4H,2’-CH2,2”CH₂),1.85–1.40(m,16H,H6,H12,Me24a,Me14a,Me4a,H26,,22-CH₂,27-CH₂),1.27(dd,6H,6’-Me,6”-Me),1.16(d,3H,28-Me),0.96(t,3H,Me12a),0.76(d,3H,Me26a)；¹³C NMR(75MHz,CDCl₃)δ205.59,173.17,154.49,139.02,137.59,134.69,133.04,132.81,131.16,124.48,121.19,120.07,118.37,117.91,117.10,97.72,96.35,94.34,81.31,80.89,80.55,78.87,77.72,76.91,76.28,73.21,70.43,68.20,68.13,68.40,67.97,66.63,57.97,56.18,45.41,40.20,39.36,39.09,36.44,35.80,35.19,34.31,33.85,26.36,19.99,19.31,18.80,18.03,14.88,13.57,12.21,11.65.HRMS:calcdfor C₅₂H₇₆O₁₆(M+H)⁺:955.5050；found,957.5052.

EXAMPLE 1.65 preparation of allyloxycarbonyl-4 "-methylamino avermectin B2a homoalkene derivative (VI)

R in formula (VI)₁Is CH₃。

Dissolving 107g (0.112 mol) of a substance shown in a formula (V) in 250mL of anhydrous dichloromethane, fully dissolving, cooling to 10 ℃, adding 24g (0.40 mol) of acetic acid, adding 80g (1.030 mol) of a methanol solution of 40 mass percent of methylamine, reacting at 10 ℃ for 2 hours, adding 2.14g (0.02 weight part) of sodium borohydride, reacting at 15 ℃ for 1 hour, washing an organic phase with dilute hydrochloric acid, a saturated sodium bicarbonate solution and saturated salt water in sequence after the reaction is finished, extracting with dichloromethane, drying with anhydrous sodium sulfate, concentrating, and passing through a column to obtain 85g of a product VI with the yield of 78%.

Structure confirmation data: 1H NMR (300MHz, CDCl)₃)δ5.8-5.85(m,5H,H-9,H-10,H-11,H-1″,CH₂＝CH-CH₂-O),5.56(m,3H,H-23,CH₂＝CH-CH₂-O),5.35-5.44(m,5H,H-15,H-19,H-3,CH₂＝CH-CH₂-O),5.08(s,1H,NH),4.92(d,1H,H-1′),4.8(s,2H,CH2-8a),4.39-4.50(m,1H,H-5),4.25-4.29(m,1H,H-5″),3.85-4.10(m,7H,H-3′,H-17,H-13,H-5′,H-4″,H-6,7-OH),3.58-3.79(m,1H,H-3″),3.31-3.49(m,11H,3″-OMe,H4,H-25,3′-OMe,N-Me),2.56(m,1H,H-4′),2.01-2.40(m,3H,H-12,H-2′),1.9(s,3H,4-Me),1.10-1.53(m,14H,H-18,H-20,H-26,H-27,14-Me,H-2″,22-CH₂),0.9-1.08(m,20H,27-Me,24-Me,26-Me,H-16,6′-Me,6″-Me,12-Me)；¹³C NMR(75MHz,CDCl₃)δ173.32,155.59,139.07,138.88,137.80,134.73,133.57,132.82,131.72,131.52,124.82,121.49,120.54,118.89,118.04,117.17,98.72,96.44,94.55,81.35,80.66,80.16,79.04,76.89,75.24,73.26,73.20,68.63,68.26,68.15,68.09,67.07,66.95,60.04,56.85,55.41,45.59,38.41,36.42,36.11,35.27,34.58,30.96,26.53,20.34,19.42,18.96,18.04,17.80,15.20,14.84,12.32,11.67.HRMS:calcd forC₅₃H₇₉NO₁₅(M+H)⁺:970.5522；found,970.5517.

EXAMPLE 1.75-hydroxy-4 "-Emamectin B2a preparation of the higher alkene derivative Compound (ic)

R in formula (VI)₁The meaning of is CH₃；

R in formula (ic)₁The meaning of is CH₃。

108g (0.112 mol) of a substance shown in a formula (VI) is dissolved in a mixed solvent of 300mL of anhydrous dichloromethane and 100mL of methanol, the mixed solvent is fully dissolved, the temperature is reduced to 0 ℃, 1.08g (0.01 weight part) of palladium tetra-triphenylphosphine is added, 2.16g (0.02 weight part) of sodium borohydride is added, the mixture reacts for 1 hour at the temperature of 0 ℃, after the reaction is finished, an organic phase is washed by dilute hydrochloric acid, saturated sodium bicarbonate solution and saturated salt water in sequence, dichloromethane is extracted, anhydrous sodium sulfate is dried, and 97g of a product IC is obtained after concentration and column passing, and the yield is 98%.

The structure validation data is as follows:¹H NMR(300MHz,CDCl₃)δ5.74(d,3H,H9,H10,4”-NH),5.39(d,4H,H3,H11,H15,H23),4.98(d,1H,5-OH),4.78(d,1H,H19),4.67(s,2H,H1’,H1”),4.30(d,1H,H5),4.11(s,1H,7-OH),4.04–3.88(m,4H,H5’,H5”,CH₂),3.86–3.51(m,4H,H3’,H3”,H13,H25),3.40(d,6H,3’-OCH₃,3”-OCH₃),3.34–3.15(m,2H,H17,H4’),2.66(s,1H,H4),2.57(s,3H,NHMe),2.54–2.45(m,1H,H4”),2.38–1.97(m,7H,H6,20-CH₂,2’-CH₂,2”CH₂),1.87(s,6H,16-CH₂,18-CH₂,22-CH₂),1.51(dd,13H,H12,Me24a,Me14a,Me4a,H26,27-CH₂),1.24(t,6H,6’-Me,6”-Me),1.16(d,3H,28-Me),0.96(t,3H,Me12a),0.76(d,3H,Me26a)；¹³C NMR(75MHz,CDCl₃)δ173.44,155.59,139.27,137.79,137.63,134.73,133.10,124.36,120.11,117.91,117.70,117.06,98.31,96.34,94.43,81.28,80.15,80.05,78.95,78.86,76.26,75.14,73.18,67.98,67.39,67.09,66.95,59.75,56.39,55.13,45.40,40.23,39.44,38.15,36.50,35.80,35.21,34.33,33.86,30.67,26.35,19.88,19.62,18.79,19.90,17.78,14.84,12.20,11.65；HRMS:calcd for C₄₉H₇₅NO₁₃(M+H)⁺:886.5311；found,886.5305。

EXAMPLE 1.8.5 preparation of allyloxycarbonyl-4 "-Aminoavermectin B2a higher alkene derivative Compound (VII)

107g (0.112 mol) of the substance represented by the formula (V) was dissolved in 350mL of anhydrous methylene chloride, and after sufficient dissolution, 85g (0.526 mol) of hexamethyldisilazane and 33g (0.112 mol) of zinc trifluoroacetate were added and reacted at 50 ℃ for 2 hours, and after cooling to 5 ℃, 150g (1.5 parts by weight) of methanol was added, and 8g (0.08 parts by weight) of sodium borohydride was added in portions and reacted at 15 ℃ for 1 hour. After the reaction, the organic phase was washed with dilute hydrochloric acid, saturated sodium bicarbonate solution, and saturated brine in this order, extracted with dichloromethane, dried over anhydrous sodium sulfate, and concentrated on a column to give 91g of product VII in 85% yield.

The structure validation data is as follows:¹H NMR(300MHz,CDCl₃)δ5.72-5.78(m,5H,H-10,H-11,H-23,CH₂＝CH-CH₂-O),5.35-5.44(m,5H,H-15,H-19,H-3,H-9,CH₂＝CH-CH₂-O),5.11(s,2H,NH₂),4.78(m,4H,H-1″,H-1′,CH₂＝CH-CH₂-O),4.69(s,2H,CH2-8a),4.40-4.42(m,1H,H-5),4.30-4.31(m,1H,H-5″),3.83-4.08(m,7H,H-3′,H-17,H-13,H-5′,H-4″,H-6,7-OH),3.52-3.71(m,1H,H-3″),3.29-3.49(m,8H,3″-OMe,H-25,3′-OMe,H4),2.52(m,1H,H-4′),2.00-2.38(m,5H,H-12,H-22,H-2′),1.88(s,3H,4-Me),1.07-1.50(m,12H,H-18,H-20,H-26,H-27,14-Me,H-2″),0.86-1.07(m,20H,27-Me,24-Me,26-Me,H-16,5′-Me,5″-Me,12-Me)；¹³C NMR(75MHz,CDCl₃)δ172.86,154.44,138.97,137.58,134.71,132.98,131.97,131.17,130.47,128.44,124.65,121.35,120.14,118.24,117.91,117.10,98.27,96.31,81.28,80.53,80.34,78.96,76.97,74.37,73.28,73.09,68.29,68.18,67.98,66.80,65.21,56.22,54.98,50.24,45.42,39.36,35.76,31.52,30.20,29.34,28.95,26.31,22.28,19.55,18.76,17.90,16.84,14.79,13.71,13.32,12.15,11.65.HRMS:calcd for C₅₂H₇₇NO₁₅(M+H)⁺:956.5366；found,956.5358

EXAMPLE 1.9.5 preparation of hydroxy-4 "-Aminoavermectin B2a higher alkene derivative Compound (Ib)

107g (0.112 mol) of the substance shown in the formula (VII) is dissolved in a mixed solvent of 300mL of anhydrous dichloromethane and 100mL of methanol, after the sufficient dissolution, the temperature is reduced to 0 ℃, 1.07g (0.01 weight part) of tetrakis-triphenylphosphine palladium is added, 2.14g (0.02 weight part) of sodium borohydride is added, the reaction is carried out for 1 hour at the temperature of 0 ℃, after the reaction is finished, the organic phase is washed by dilute hydrochloric acid, saturated sodium bicarbonate solution and saturated salt water in sequence, dichloromethane is extracted, anhydrous sodium sulfate is dried, and the product Ib is concentrated and passes through a column to obtain 93g of the product I b with the yield of 95%.

The structure validation data is as follows: 1H NMR (300MHz, CDCl)₃)δ5.72-5.78(m,4H,H-10,H-11,H-1″,H3),5.56(d,1H,H-23),5.35-5.44(m,3H,H-15,H-19,H-9),5.11(s,2H,NH2),4.78(m,2H,H-1′,5-OH),4.69(s,2H,CH2-8a),4.40-4.42(m,1H,H-5),4.30-4.31(m,1H,H-5″),3.83-4.08(m,7H,H-3′,H-17,H-13,H-5′,H-4″,H-6,7-OH),3.52-3.71(m,1H,H-3″),3.29-3.49(m,8H,3″-OMe,H-4,H-25,3′-OMe),2.52(m,3H,H-4′,22-CH₂),2.00-2.38(m,3H,H-12,H-2′),1.88(s,3H,4-Me),1.07-1.50(m,12H,H-18,H-20,H-26,H-27,14-Me,H-2″),0.86-1.07(m,20H,27-Me,24-Me,26-Me,H-16,5′-Me,5″-Me,12-Me)；¹³C NMR(75MHz,CDCl₃)δ173.56,139.30,137.78,137.70,134.73,133.09,124.38,120.2,117.92,117.70,117.06,98.38,96.36,94.42,81.28,80.19,80.06,79.03,78.75,76.86,75.01,73.20,68.14,68.06,68.00,67.40,66.90,65.89,56.35,54.94,50.55,45.41,39.44,36.62,35.81,35.22,34.35,33.85,29.33,26.36,19.91,19.63,18.79,17.95,16.96,14.85,12.21,11.65.HRMS:calcdfor C₄₈H₇₃NO₁₃(M+H)⁺:872.5155；found,872.5145

EXAMPLE 1.10.5 preparation of allyloxycarbonyl-4 "-acetamidoavermectin B2a higher ene derivative Compound (VIII)

R in the formula (VII)₂The meaning of is CH₃

107g (0.112 mol) of the substance represented by the formula (VII) was added to 200mL of anhydrous dichloromethane and 53g (0.67 mol) of pyridine, and the mixture was sufficiently dissolved. 61g (0.6 mol) of acetic anhydride was added dropwise at 20 ℃ and reacted overnight at 20 ℃. After the reaction is finished, the organic phase is washed by dilute hydrochloric acid, saturated sodium bicarbonate solution and saturated salt water in sequence, extracted by dichloromethane, dried by anhydrous sodium sulfate and concentrated by a column to obtain 107g of a product VIII with the yield of 96%.

The structure validation data is as follows:¹H NMR(300MHz,CDCl₃)δ5.68～6.05(m,4H,H9,H10,H11,CH₂＝CH-CH₂O),5.52～5.63(m,2H,H3,H23),5.22～5.43(m,5H,H5,H1″,H19, ₂CH＝CH-CH₂O),5.11(s,1H,NH),4.92～5.06(m,1H,H15),4.59～4.86(m,5H,H1′,H8ax2,CH₂＝CH- ₂CHO),4.09-4.16(m,2H,H13,7-OH),3.94(m,1H,H4),3.71～4.03(m,6H,H5″,H5′,H6,H17,H3″,H3′),3.30～3.48(m,10H,H25,3″-OCH₃,3′-OCH₃,R2-CH₃),3.22(m,1H,H4′),3.14(t,1H,H4″),2.45～2.60(m,1H,H12),1.77～2.39(m,13H,H16x2,H2′,H2″,H18,Me4a,H20),1.45～1.69(m,8H,Me14a,H26,H27x2,H22x2),1.13～1.32(m,9H,Me6′,Me6″,Me12a),0.84～1.01(m,9H,Me28,Me24a,Me26a)；¹³C NMR(75MHz,CDCl₃)δ173.15,170.31,154.50,138.97,137.65,134.72,133.04,132.80,131.17,124.44,121.21,120.10,118.36,117.89,117.11,98.31,96.35,94.30,81.25,80.72,80.56,78.99,76.89,73.23,73.18,72.97,68.40,68.20,68.13,67.98,66.69,65.16,56.30,55.73,48.11,45.43,40.22,39.39,36.44,35.80,35.20,34.32,33.85,31.55,26.35,23.13,19.96,19.31,18.79,17.96,16.72,14.86,12.20,11.65.HRMS:calcd for C₅₄H₇₉NO₁₆(M+H)⁺:998.5472；found,998.5461.

EXAMPLE 1.11.5 preparation of 4 '-hydroxy-4' -Acetaminoavermectin B2a higher alkene derivative Compound (Id)

R in the formula (VIII)₂The meaning of is CH₃；

R in formula (Id)₂The meaning of is CH₃。

112g (0.112 mol) of a substance shown in a formula (VIII) is dissolved in a mixed solvent of 300mL of anhydrous dichloromethane and 100mL of methanol, after the substance is fully dissolved, the temperature is reduced to 0 ℃, 1.1g (0.01 weight part) of tetra-triphenylphosphine palladium is added, 4.4g (0.04 weight part) of sodium borohydride is added, the reaction is carried out for 1 hour at the temperature of 0 ℃, after the reaction is finished, an organic phase is washed by dilute hydrochloric acid, saturated sodium bicarbonate solution and saturated salt water in sequence, dichloromethane is extracted, anhydrous sodium sulfate is dried, and 98g of a product Id1 is obtained by concentration and column chromatography, wherein the yield is 96%.¹HNMR(300MHz,CDCl₃)δ5.69～5.87(m,5H,H3,H9,H10,H11,H23),5.35～5.48(m,2H,H1″,H19),5.11(s,1H,NH),4.91～5.08(m,1H,H15),4.67-4.84(m,3H,H8ax2,H1′),3.95-4.06(m,4H,5-OH,7-OH,H5,H6),3.74～3.89(m,3H,H13,H5″,H5′),3.41～3.68(m,11H,H17,H25,H4,H3″,H3′,3″-OCH₃,3′-OCH₃),3.27-3.18(m,2H,H4′,H4″),2.51～2.62(m,1H,H12),2.21～2.41(m,6H,H16x2,H2′,H2″),1.84～2.05(m,7H,H18,Me4a,H20),1.40～1.65(m,8H,Me14a,H26,H27x2,H22x2),1.15～1.36(m,12H,Me6′,Me6″,Me12a,R₂-CH₃),0.84～1.03(m,9H,H28,Me24a,Me26a)；¹³C NMR(75MHz,CDCl₃)δ173.32,170.37,137.61,134.67,133.00,131.99,124.67,124.43,120.06,117.95,117.11,98.30,96.33,94.32,81.29,80.72,80.05,78.98,76.91,73.13,72.97,68.01,67.36,66.69,65.15,56.24,55.67,48.11,45.39,39.41,35.80,31.54,30.22,29.65,29.31,28.97,27.05,26.33,23.02,22.30,19.55,18.81,18.75 17.93,16.68,14.82,13.72,13.33,12.17,11.66.HRMS:calcd forC₅₀H₇₅NO₁₄(M+H)⁺:914.5260；found,914.5251

Example 1.12 preparation of Compound ic benzoate

By the formula (ic) (R1 has the meaning CH₃) 100g (0.112 mol) of the indicated substance are dissolved in 300mL of anhydrous dichloromethane, 14g (0.114 mol) of benzoic acid are added, and the mixture is concentrated and dried to give the compound of the formula (ic) (R1 represents CH₃) Salt-forming products of the indicated species. The single crystal structure and data of the salt-forming product of compound Ic are shown in fig. 18, fig. 19, fig. 20, fig. 21, and tables 1,2 and 3). The structure validation data is as follows:¹H NMR(300MHz,CDCl₃)δ8.15–8.03(m,2H,ph-H),7.49(s,1H,ph-H),7.44–7.34(m,2H,ph-H),5.86(d,1H,H9),5.75–5.62(m,4H,H10,H11,4”-NH₂),5.39(d,3H,H3,H15,H23),4.98(d,1H,5-OH),4.77(d,1H,H19),4.67(s,2H,H1’,H1”),4.30(d,1H,H5),4.03(d,1H,7-OH),3.98–3.47(m,8H,H5’,H5”,H3’,H3”,H13,H25,CH₂),3.40(d,6H,3’-OCH₃,3”-OCH₃),3.28(dd,1H,H4’),3.21(t,1H,H17),2.92(d,1H,H4),2.69(s,3H,NHMe),2.58–2.46(m,1H,H4”),2.42–1.37(m,26H,H6,20-CH₂,2’-CH₂,2”CH₂,16-CH₂,18-CH2,22-CH₂,13H,H12,Me24a,Me14a,Me4a,H26,27-CH₂),1.34(d,3H,6”-Me),1.21(d,3H,6’-Me),1.15(d,3H,28-Me),0.95(t,3H,Me12a),0.76(d,3H,Me26a)；¹³C NMR(75MHz,CDCl₃)δ173.43,170.70,139.29,137.70,137.60,134.72,133.08,131.6,129.50(2C),127.66(2C),124.39,120.10,117.91,117.70,117.06,98.13,96.35,94.42,81.30,80.49,80.05,78.84,76.29,74.41,73.17,68.09,67.99,67.39,66.85,66.15,59.54,56.32,55.36,45.42,40.25,39.41,36.49,35.79,35.20,34.29,33.85,30.53,26.35,23.50,19.90,19.60,18.79,17.87,17.45,14.84,13.70,13.28,12.20,11.66.HRMS:calcd for C₅₆H₈₁NO₁₅(M+H)⁺:1008.5679；found,1008.5681。

TABLE 1 Single Crystal diffraction specific test conditions and related parameters

TABLE 2 partial bond length in single crystal

TABLE 3 Key Angle names and values

The compounds of the invention are represented by the general formula (I):

the meaning of R in formula (I) is:

r is hydroxy (Ia), R is amino (Ib), R is NHR₁(ic) or R is NHCOR₂(id); wherein: the definitions of R1, R2 in the radicals of the compounds (ic) and (id) are specified above.

Typical formulation compositions and their preparation are as follows:

formulation examples for crop protection (% percent by weight)

The active ingredient described in the following examples may be at least one of the compounds of formula I.

Example 2.1: emulsifiable concentrate

Example 1: emulsifiable concentrate	a	b	c
				Active ingredient	5％	15％	20％
Calcium dodecyl benzene sulfonate	5％	8％	6％
				Castor oil polyglycol ether	5％	-	-
(36mol ethylene oxide, solvent)	-	-	-
				Tributyl phenol polyglycol ether	-	12％	4％
(30mol ethylene oxide, solvent)	-	-	-
				Cyclohexanone	-	15％	20％
Xylene mixture	75％	50％	50％

The finely ground active ingredients and additives are mixed to give an emulsifiable concentrate which can be diluted with water to give an emulsion of the desired concentration.

Example 2.2: solutions of

The finely ground active ingredient and additives are mixed to produce a solution suitable for use in the form of microdroplets.

Example 2.3: granules

Example 3: granules	a	b	c
				Active ingredient	5％	15％	20％
Kaolin clay	93％	-	55％
				Highly dispersed silicic acid	2％	-	7％
Silicon magnesia	-	85％	8％

The active ingredient is dissolved in dichloromethane, the solution is sprayed onto the carrier mixture and the solvent is evaporated off under reduced pressure.

Example 2.4: wettable powder

Mixing the active ingredient and the additive together, grinding the mixture in a suitable mill,

wettable powders are produced which can be diluted with water to form suspensions of the desired concentration.

Example 2.5: emulsifiable concentrate

Active ingredient	10％
		Octyl phenol polyglycol ether (4-5 mol ethylene oxide)	3％
Calcium dodecyl benzene sulfonate	3％
		Castor oil polyglycol ether (36mol ethylene oxide)	4％
Cyclohexanone	35％
		Xylene mixture	55％

Example 2.6: granules

Active ingredient	10％
		Lignosulfonic acid sodium salt	3％
Carboxymethyl cellulose
		2％
Kaolin clay			85％

The active ingredient and the additives are mixed together, the mixture is ground, moistened with water, extruded, granulated and the granules are dried in an air stream.

Example 2.7: coated granules

Active ingredient	4％
		Polyethylene glycol (molecular weight 200)	4％
Kaolin clay	82％

The finely ground active ingredient is uniformly coated onto the kaolin moistened with polyethylene glycol in a mixer to give dust-free coated granules.

Example 2.8: suspension concentrate

Active ingredient	40％
		Ethylene glycol
	10％
		Nonyl phenol polyglycol ether (or 15mo1 ethylene oxide)	6％
Lignosulfonic acid sodium salt	10％
		Carboxymethyl cellulose	1％
Formalin (40%)	5％
		Silicone oil emulsion (75%)	5％
Water (W)	32％

Mixing the finely ground active ingredient with additives to obtain a suspension concentrate, diluting the suspension concentrate with water

Agent, which can produce a desired concentration of suspending agent.

Example 2.9: powder preparation

Example 9: powder preparation	a	b
			Active ingredient	5％	10％
Talc	95％	-
			Divot soil	-	90％

The active ingredient and the segment stick are combined and ground in a suitable mill to obtain a powder for use.

3, biological activity determination:

3.1 test methods

3.2, test conditions

Insecticide laboratory, normal room temperature.

The temperature, humidity and illumination of the pesticide observation chamber can be adjusted as required.

Greenhouse, all-weather sunlight greenhouse.

3.3, preparing the liquid medicine

Accurately weighing the test medicament by using an electronic analytical balance, completely dissolving the original medicament by using a solvent, preparing mother liquor with the required concentration by using Tween 80 water with the mass fraction of 0.1% as required, and diluting the mother liquor into a series of liquid medicaments with a certain concentration gradient according to the experimental design dosage.

3.4 biological Activity measurement example

Example 3.4.1 determination of Meloidogyne incognita Activity

A 24-well plate method was used. Adding 0.5ml of the prepared bacterial suspension (more than 200 heads of second-instar root-knot nematodes) into a 24-well plate, adding 0.5ml of liquid medicine according to the sequence from low to high in the experimental design, repeating for 4 times, and arranging a blank control.

Example 3.4.2 determination of Aphis fabae Activity

The spraying method is adopted. The broad bean seedlings with the 2-day-old Aphis citricola are taken, the prepared liquid medicine is uniformly sprayed on the broad bean seedlings and the seedlings by an airrbrush manual sprayer from low to high according to the test design, the liquid is preferably not dropped, the broad bean seedlings are naturally dried in the shade and then placed in an observation room for culture, and the process is repeated for 3 times, and a blank control is additionally arranged.

Example 3.4.3 determination of armyworm Activity

The spraying method is adopted. Cutting the middle leaves of fresh corns cultivated in a greenhouse into 3cm small sections, uniformly spraying prepared liquid medicine on the front and back surfaces of the leaves by using an airrbrush manual sprayer according to the sequence from low to high in experimental design, placing the leaves in a culture dish with filter paper and the diameter of 6cm, naturally drying the leaves in the shade, then inoculating regular healthy test insects, repeating the steps for 3 times every 10 times, and additionally arranging a blank control. Example 3.4.4 assay of Plutella xylostella Activity

The spraying method is adopted. Removing a surface wax layer from leaves of cabbage cultivated in a greenhouse, punching the leaves into a circular leaf disc with the diameter of 3cm by using a puncher, uniformly spraying prepared liquid medicine on the front and back surfaces of the leaves by using an airbrush manual sprayer according to the sequence of the experimental design concentration from low to high, placing the leaves into a culture dish with the diameter of 6cm and containing filter paper, naturally drying the leaves in the shade, inoculating regular healthy test insects, repeating for 3 times every 10 times, and additionally arranging a blank control.

Example 3.4.5 assay of spodoptera exigua Activity

The spraying method is adopted. Removing a surface wax layer from cabbage leaves cultured in a greenhouse, punching the leaves into a circular leaf disc with the diameter of 3cm by using a puncher, uniformly spraying prepared liquid medicine on the front and back surfaces of the leaves by using an airbrush manual sprayer according to the sequence from low to high of the experimental design, placing the leaves in a culture dish with the diameter of 6cm and containing filter paper, naturally drying the leaves in the shade, inoculating regular healthy test insects, repeating the steps for 3 times every 10 times, and additionally arranging a blank control.

Example 3.4.6 Asiatic corn borer Activity assay

The spraying method is adopted. Cutting fresh corn stalks cultivated in a greenhouse into 4cm small sections, uniformly spraying the prepared liquid medicine on the corn stalks by using an airbrush manual sprayer according to the sequence from low to high in experimental design, placing the corn stalks in a culture dish with filter paper and the diameter of 6cm, naturally drying in the shade, inoculating regular healthy test insects, repeating the steps for 3 times every 10 times, and additionally arranging a blank control.

Example 3.4.7 measurement of thrips palmi Activity

The spraying method is adopted. Taking fresh eggplant leaves, punching the leaves into a circular leaf disc with the diameter of 30.cm by using a puncher, carrying out spraying treatment on the prepared liquid medicine by using an airbrish manual sprayer according to the sequence from low to high in the experimental design, inoculating 3-year-old nymphs of thrips after the leaves are naturally dried in the shade, sealing by using a sealing film for every 15 heads, repeating the experiment for 3 times, and additionally arranging a blank control.

Example 3.4.8 Tetranychus cinnabarinus Activity assay

The spraying method is adopted. Selecting kidney bean seedlings with two true leaves, and transplanting the kidney bean seedlings into culture paper cups, wherein one kidney bean seedling is planted in each cup. After the transplanted seedlings recover to normal growth, heart leaves and a true leaf are cut off three hours before treatment, a proper amount of adult female mites are grafted on the heart leaves and the true leaves, the base number is recorded, the operation is repeated for 3 times, and blank control is additionally arranged.

The following table shows the results of the bioactivity assays:

Claims

1. a compound or agriculturally acceptable salt of formula (I):

in the formula (I), R is selected from any one of the following groups: hydroxy, amino, NHR₁And NHCOR₂；

Wherein: NHR₁And NHCOR₂In the radical R₁、R₂Is defined as follows:

R₁、R₂the same or different, each independently represented by: C1-C6 alkyl substituted or unsubstituted by halogen or C1-C3 alkyl, C3-C6 alkenyl substituted or unsubstituted by halogen or C1-C3 alkyl, and C3-C6 alkynyl substituted or unsubstituted by halogen or C1-C3 alkyl.

2. The compound or agriculturally pharmaceutically acceptable salt of claim 1, characterized by: the compound shown in the formula (I) is selected from any of the following compounds:

1) a compound in which R in the formula (I) is hydroxyl;

2) a compound in which R in the formula (I) is amino;

3) r in the formula (I) is NHR₁And R is₁A compound that is methyl;

4) r in the formula (I) is NHR₁And R is₁A compound which is ethyl;

5) r in the formula (I) is NHCOR₂And R is₂A compound that is methyl;

6) r in the formula (I) is NHCOR₂And R is₂A compound which is ethyl.

3. The compound or agriculturally pharmaceutically acceptable salt according to claim 1 or 2, characterized by: the salt is organic acid salt or inorganic acid salt, including benzoate, substituted benzoate, citrate, lactate, aldonic acid salt, hydrochloride or sulfate.

4. A process for preparing a compound of formula (I) as defined in claim 1 wherein R is hydroxy, comprising the steps of:

A) in an organic solvent, in the presence of an alkaline medium, reacting abamectin B2a with a protective reagent, namely allyl chloroformate to obtain a compound shown as a formula (II);

B) dehydrating and eliminating C23-OH and C24-H in the compound shown in the formula (II) in the presence of an organic base, an eliminating reagent and an eliminating catalyst to form an olefinic bond, and isomerizing the olefinic bond between C3 and C4 into C2 and C3 olefinic bonds to obtain the compound shown in the formula (III);

C) in an organic solvent, in the presence of a catalyst of palladium tetratriphenylphosphine, carrying out deprotection reaction on a compound shown as a formula (III) and sodium borohydride to obtain a compound shown as a formula (Ia), namely a compound shown as a formula (I) in which R is hydroxyl;

5. the method of claim 4, wherein:

in the step A), the organic solvent is at least one selected from dichloromethane, 1, 2-dichloroethane, isopropyl acetate, ethyl acetate, n-hexane, benzene, toluene, chloroform, tetrachloromethane, petroleum ether, chlorobenzene, dioxane and tetrahydrofuran, preferably at least one selected from dichloromethane, 1, 2-dichloroethane and isopropyl acetate, and most preferably dichloromethane; the dosage of the organic solvent can be 1-100L, preferably 2-10L, and more preferably 3-5L relative to 1 mol of abamectin B2 a;

in the step A), the alkaline medium is at least one selected from pyridine, triethylamine, ethylenediamine, tetramethylethylenediamine, triethylenediamine and N-methylmorpholine; preferably at least one of pyridine, triethylamine and tetramethylethylenediamine, most preferably tetramethylethylenediamine; the dosage of the alkaline medium is 1 to 50 mol, preferably 1.05 to 20 mol, more preferably 1.2 to 10 mol relative to 1 mol of abamectin B2 a;

the amount of the protecting reagent, namely the allyl chloroformate, can be 2 to 12 moles, preferably 2 to 6 moles, and more preferably 2 to 3 moles, relative to 1 mole of the abamectin B2 a;

the reaction conditions of the reaction include: the temperature can be-30 ℃ to 30 ℃, preferably-30 ℃ to 10 ℃, and the time is 1-10 hours, preferably 1-2 hours;

in the step B), the organic solvent is at least one selected from dichloromethane, n-hexane, benzene, toluene, trichloromethane, tetrachloromethane, petroleum ether, chlorobenzene, dioxane, methanol and tetrahydrofuran, preferably at least one selected from dichloromethane, trichloromethane and tetrahydrofuran, and most preferably dichloromethane; the amount of the organic solvent to be used may be 1 to 100L, preferably 2 to 10L, more preferably 3 to 5L, relative to 1 mole of the compound represented by the formula (II);

in the step B), the elimination reagent is selected from at least one of acetic anhydride, trifluoroacetic anhydride, trifluoromethanesulfonic anhydride, methanesulfonyl chloride, p-methylbenzenesulfonyl chloride and benzenesulfonyl chloride; preferably trifluoromethanesulfonic anhydride, methanesulfonyl chloride, most preferably trifluoromethanesulfonic anhydride; the elimination reagent is used in an amount of 0.5 to 20 moles, preferably 1 to 10 moles, more preferably 1 to 5 moles, relative to 1 mole of the compound represented by the formula (II);

in the step B), the organic base is selected from at least one of pyridine, triethylamine, ethylenediamine, tetramethylethylenediamine, triethylenediamine, N-methylmorpholine, tetramethylammonium hydroxide, potassium tert-butoxide, monoethanolamine and triethanolamine; preferably at least one selected from pyridine, triethylamine and tetramethylethylenediamine, most preferably pyridine. The organic base is used in an amount of 1 to 50 moles, preferably 1.05 to 20 moles, more preferably 1.2 to 10 moles, relative to 1 mole of the compound represented by the formula (II);

in the step B), the elimination catalyst is at least one of DBU (1, 8-diazabicycloundec-7-ene), DMAP (4-dimethylaminopyridine), sodium sulfate, potassium sulfate and 4-methylpyridine, and is preferably selected from DBU and DMAP; the amount of the catalyst to be used is 0.1 to 5 moles, preferably 0.1 to 2 moles, more preferably 0.1 to 1.5 moles, relative to 1 mole of the compound represented by the formula (II);

in the step B), the reaction conditions comprise: the temperature is-50 ℃ to 40 ℃, preferably-30 ℃ to 20 ℃, more preferably-5 ℃ to-0 ℃; for a period of 1 to 10 hours, preferably 2 to 3 hours; the reaction is preferably carried out in an inert atmosphere, such as a nitrogen atmosphere.

In the step C), the organic solvent is at least one selected from dichloromethane, n-hexane, benzene, toluene, trichloromethane, tetrachloromethane, petroleum ether, chlorobenzene, dioxane, methanol and tetrahydrofuran, preferably at least one selected from dichloromethane, trichloromethane and tetrahydrofuran, and most preferably dichloromethane; the amount of the organic solvent to be used may be 1 to 100L, preferably 2 to 10L, more preferably 3 to 5L, relative to 1 mole of the compound represented by the formula (III);

in the step C), the amount of the catalyst tetrakistriphenylphosphine palladium is 0.001 to 0.1 part by mass, preferably 0.005 to 0.03 part by mass, and more preferably 0.01 to 0.02 part by mass, relative to 1 part by mass of the compound represented by the formula (III); the amount of sodium borohydride to be used is 0.001 to 0.1 part by mass, preferably 0.01 to 0.04 part by mass, and more preferably 0.02 to 0.03 part by mass, relative to 1 part by mass of the compound represented by the formula (III).

The reaction conditions of the deprotection reaction include: the temperature is-10 ℃ to 20 ℃, preferably 0 ℃ to 5 ℃; the time is 0.5 to 4 hours, preferably 1 to 2 hours.

6. The compound of claim 1 of formula (I) wherein R is NHR₁The process for the preparation of a compound of (1), comprising the steps of:

D) reacting a compound shown as a formula (Ia) with a protecting reagent, namely allyl chloroformate, in an organic solvent in the presence of an alkaline medium to obtain a compound shown as a formula (IV);

E) reacting the formula (IV) with an oxidation reagent dimethyl sulfoxide and acyl chloride in an organic solvent in the presence of alkali to obtain a compound shown in a formula (V);

F) reacting formula (V) with an alkyl amine R in an organic solvent under the catalysis of Lewis acid₁NH₂Reacting to ensure that C4 '-carbonyl in the formula (V) is aminated to C4' -alkylene amino, and then adding reducing agent sodium borohydride to ensure that C4 '-alkylene amino is reduced to C4' -alkylamino, thus obtaining the compound shown in the formula (VI);

wherein R is₁NH₂And R in the formula (VI)₁Is as defined in formula I;

G) reacting a compound of formula (VI) with sodium borohydride in an organic solvent in the presence of palladium triphenylphosphine as a catalyst to remove a C5-OH protecting group Alloc to obtain a compound of formula (ic), wherein R in the formula (I) is NHR₁A compound as defined under (1);

7. the method of claim 6, wherein:

in the step D), the organic solvent is at least one selected from dichloromethane, 1, 2-dichloroethane, isopropyl acetate, ethyl acetate, n-hexane, benzene, toluene, chloroform, tetrachloromethane, petroleum ether, chlorobenzene, dioxane and tetrahydrofuran, preferably at least one selected from dichloromethane, 1, 2-dichloroethane and isopropyl acetate, and most preferably dichloromethane; the amount of the organic solvent to be used is 1 to 100L, preferably 2 to 10L, more preferably 3 to 5L, relative to 1 mole of the compound represented by the formula (Ia);

in the step D), the alkaline medium is selected from at least one of pyridine, triethylamine, ethylenediamine, tetramethylethylenediamine, triethylenediamine and N-methylmorpholine; preferably selected from pyridine, triethylamine, tetramethylethylenediamine, most preferably tetramethylethylenediamine; the amount of the basic medium to be used is 1 to 10 moles, preferably 1.05 to 5 moles, more preferably 1.2 to 3 moles, relative to 1 mole of the compound represented by the formula (Ia);

wherein the amount of the protecting reagent, namely, dilute propyl chloroformate, is 1 to 8 moles, preferably 1 to 3 moles, and more preferably 1 to 1.2 moles, relative to 1 mole of the compound represented by the formula (Ia);

suitable reaction conditions include: the temperature is-30 ℃ to 30 ℃ and the time is 0.5 to 24 hours;

in the step E, the organic solvent is at least one selected from dichloromethane, n-hexane, benzene, toluene, chloroform, tetrachloromethane, petroleum ether, chlorobenzene, dioxane and tetrahydrofuran, preferably at least one selected from dichloromethane, chloroform and tetrahydrofuran, and most preferably dichloromethane; the amount of the organic solvent to be used may be 1 to 100L, preferably 2 to 10L, more preferably 3 to 5L, relative to 1 mole of the compound represented by the formula (IV);

in the step E, the base is at least one selected from pyridine, triethylamine, ethylenediamine, tetramethylethylenediamine, triethylenediamine and N-methylmorpholine; preferably selected from pyridine, triethylamine, tetramethylethylenediamine, most preferably tetramethylethylenediamine; the amount of the base to be used is 1 to 10 moles, preferably 1.05 to 5 moles, more preferably 1.2 to 3 moles, relative to 1 mole of the compound represented by the formula (IV);

wherein the amount of the oxidizing reagent dimethyl sulfoxide is 1 to 8 moles, preferably 2 to 5 moles, and more preferably 2.8 to 3 moles, based on 1 mole of the compound represented by the formula (IV); the dosage of the phenyl dichlorophosphate is 0.5-6 mol, preferably 0.8-5 mol, more preferably 1-2 mol;

suitable reaction conditions include: the temperature is-30 ℃ to 0 ℃, preferably-20 ℃ to-10 ℃, and the time is 0.5-2 hours, preferably 0.6-1 hour;

in the step F), the organic solvent is at least one selected from dichloromethane, 1, 2-dichloroethane, isopropyl acetate, ethyl acetate, n-hexane, benzene, toluene, chloroform, tetrachloromethane, petroleum ether, chlorobenzene, dioxane and tetrahydrofuran, preferably at least one selected from dichloromethane, 1, 2-dichloroethane and isopropyl acetate, and most preferably dichloromethane; the amount of the organic solvent to be used is 1 to 100L, preferably 1 to 10L, more preferably 1 to 5L, relative to 1 mole of the compound represented by the formula (V);

wherein the Lewis acid is selected from at least one of acetic acid, propionic acid, zinc trifluoroacetate, zinc chloride, zinc p-toluenesulfonate, boron trifluoride, aluminum chloride, ferric chloride and antimony pentafluoride, preferably at least one of acetic acid, zinc chloride and zinc trifluoroacetate, and most preferably acetic acid and/or zinc trifluoroacetate(ii) a The amount of the Lewis acid to be used is 0.01 to 10 mol, preferably 0.05 to 5 mol, more preferably 0.10 to 4 mol, relative to 1 mol of the compound represented by the formula (V); alkylamino (R)₁NH₂) Is used in an amount of 1.5 to 50 moles, preferably 3 to 20 moles, more preferably 5 to 10 moles; the reducing agent sodium borohydride is used in an amount of 0.001 to 0.5 parts by mass, preferably 0.005 to 0.3 parts by mass, more preferably 0.01 to 0.02 parts by mass, relative to 1 part by mass of the compound represented by formula (V);

suitable amination, reduction reaction conditions include: the temperature is-30 ℃ to 50 ℃, preferably 5 ℃ to 25 ℃, more preferably 10 ℃ to 15 ℃, and the time is 0.5 to 8 hours, preferably 0.5 to 2 hours;

in the step G), the organic solvent is at least one selected from dichloromethane, 1, 2-dichloroethane, methanol, isopropyl acetate, ethyl acetate, n-hexane, benzene, toluene, chloroform, tetrachloromethane, petroleum ether, chlorobenzene, dioxane and tetrahydrofuran, preferably at least one selected from dichloromethane, 1, 2-dichloroethane, methanol and isopropyl acetate, and most preferably a mixed solvent of dichloromethane and methanol, wherein the volume ratio of the two solvents is 10: 1-1: 1; the amount of the organic solvent used is 1 to 100L, preferably 2 to 10L, and more preferably 3 to 5L, relative to 1 mole of the compound represented by the formula (VI);

wherein the amount of the catalyst tetrakis-triphenylphosphorated-palladium is 0.001 to 0.1 part by mass, preferably 0.005 to 0.03 part by mass, more preferably 0.01 to 0.02 part by mass, relative to 1 part by mass of the compound represented by the formula (VI); the amount of sodium borohydride is 0.001-0.1 parts by mass, preferably 0.01-0.04 parts by mass, more preferably 0.02-0.03 parts by mass;

8. A process for the preparation of a compound of formula (I) as claimed in claim 1 wherein R is amino, comprising the steps of:

H) reacting the compound shown in the formula (V) with hexamethyldisilazane in an organic solvent under the catalysis of Lewis acid to ensure that C4 '-carbonyl in the formula (V) is aminated to C4' -imino, and then adding methanol and a reducing agent sodium borohydride to ensure that C4 '-imino is reduced to C4' -amino to obtain the compound shown in the formula (VII);

I) in an organic solvent, in the presence of a catalyst of palladium tetratriphenylphosphine, reacting a compound shown as a formula (VII) with sodium borohydride, and removing a protecting group Alloc of C5-OH to obtain a compound shown as a formula (Ib), namely a compound defined when R is amino in the formula (I);

9. the method of claim 8, wherein:

in the step H), the organic solvent is at least one selected from dichloromethane, 1, 2-dichloroethane, isopropyl acetate, ethyl acetate, n-hexane, benzene, toluene, chloroform, tetrachloromethane, petroleum ether, chlorobenzene, dioxane and tetrahydrofuran, preferably at least one selected from dichloromethane, 1, 2-dichloroethane and isopropyl acetate, and most preferably dichloromethane; the amount of the organic solvent to be used is 1 to 100L, preferably 2 to 10L, more preferably 3 to 5L, relative to 1 mole of the compound represented by the formula (V);

in the step H), the Lewis acid is selected from at least one of zinc trifluoroacetate, zinc chloride, zinc p-toluenesulfonate, boron trifluoride, aluminum chloride, ferric chloride and antimony pentafluoride, preferably at least one of zinc chloride, zinc p-toluenesulfonate and zinc trifluoroacetate, and most preferably zinc trifluoroacetate; the amount of the Lewis acid to be used is 0.01 to 10 moles, preferably 0.05 to 5 moles, more preferably 0.10 to 3 moles, based on 1 mole of the compound represented by the formula (V); the hexamethyldisilazane is used in an amount of 1.5 to 50 moles, preferably 3 to 20 moles, more preferably 4.5 to 10 moles; the amount of the reducing agent sodium borohydride to be used is 0.001 to 0.5 parts by mass, preferably 0.005 to 0.4 parts by mass, more preferably 0.01 to 0.02 parts by mass, relative to 1 part by mass of the compound represented by the formula (V); the amount of the methanol is 0.5 to 5 parts by mass, preferably 1 to 3 parts by mass, and more preferably 1.5 to 2 parts by mass;

suitable amination, reduction reaction conditions include: the temperature is 0-80 ℃, preferably 5-70 ℃, and the time is 1-8 hours, preferably 1-2 hours;

in the step I), the organic solvent is at least one selected from dichloromethane, 1, 2-dichloroethane, methanol, isopropyl acetate, ethyl acetate, n-hexane, benzene, toluene, chloroform, tetrachloromethane, petroleum ether, chlorobenzene, dioxane and tetrahydrofuran, preferably at least one selected from dichloromethane, 1, 2-dichloroethane, methanol and isopropyl acetate, and most preferably a mixed solvent of dichloromethane and methanol, and the volume ratio of the two solvents may be 10: 1-1: 1, the amount of the organic solvent used is 1 to 100L, preferably 2 to 10L, more preferably 3 to 5L, per 1 mol of the compound represented by the formula (VII);

in the step I), the amount of the catalyst tetrakistriphenylphosphine palladium may be 0.001 to 0.1 part by mass, preferably 0.005 to 0.03 part by mass, more preferably 0.01 to 0.02 part by mass, relative to 1 part by mass of the compound represented by the formula (VII); the amount of sodium borohydride is 0.001-0.1 parts by mass, preferably 0.01-0.04 parts by mass, more preferably 0.02-0.03 parts by mass;

suitable deprotection reaction conditions include: the temperature is-10 ℃ to 20 ℃, preferably 0 ℃ to 5 ℃, and the time is 0.5 to 4 hours, preferably 1 to 2 hours.

10. R in formula (I) according to claim 1 is NHCOR₂The process for the preparation of a compound of (1), comprising the steps of:

J) reacting the formula (VII) with an acylating reagent anhydride or acyl chloride in an organic solvent in the presence of alkali to perform acylation reaction on C4' -amino in the formula (VII) to obtain a compound shown in a formula (VIII);

wherein R in the formula (VIII)₂Is as defined in formula I;

K) in thatIn an organic solvent, in the presence of a catalyst of palladium tetratriphenylphosphine, reacting a compound shown as a formula (VIII) with sodium borohydride, removing a protective group Alloc of C5-OH to obtain a compound shown as a formula (Id), wherein R in the formula (I) is NHCOR₂A compound as defined under (1);

11. the method of claim 10, wherein:

in the step J), the organic solvent is at least one selected from dichloromethane, 1, 2-dichloroethane, isopropyl acetate, ethyl acetate, n-hexane, benzene, toluene, chloroform, tetrachloromethane, petroleum ether, chlorobenzene, dioxane and tetrahydrofuran, preferably at least one selected from dichloromethane, 1, 2-dichloroethane and isopropyl acetate, and most preferably dichloromethane; the amount of the organic solvent to be used may be 1 to 100L, preferably 1 to 10L, more preferably 1 to 5L, relative to 1 mole of the compound represented by the formula (VII);

in the step J), the alkaline medium is at least one selected from pyridine, triethylamine, ethylenediamine, tetramethylethylenediamine, triethylenediamine and N-methylmorpholine; preferably selected from pyridine, triethylamine, tetramethylethylenediamine, most preferably pyridine; the amount of the basic medium to be used is 0.1 to 10 moles, preferably 0.1 to 5 moles, more preferably 0.1 to 3 moles, relative to 1 mole of the compound represented by the formula (VII);

the acylating agent anhydride or acid chloride is used in an amount of 0.1 to 8 moles, preferably 0.1 to 3 moles, more preferably 0.1 to 1.2 moles, based on 1 mole of the compound represented by the formula (VII);

suitable acylation reaction conditions include: the temperature is-30-50 ℃, preferably 0-30 ℃, and the time is 1-30 hours, preferably 1-24 hours;

in the step K), the organic solvent is at least one selected from dichloromethane, 1, 2-dichloroethane, methanol, isopropyl acetate, ethyl acetate, n-hexane, benzene, toluene, chloroform, tetrachloromethane, petroleum ether, chlorobenzene, dioxane and tetrahydrofuran, preferably at least one selected from dichloromethane, 1, 2-dichloroethane, methanol and isopropyl acetate, and most preferably a mixed solvent of dichloromethane and methanol, wherein the volume ratio of the two is (10-1): 1; the amount of the organic solvent to be used may be 1 to 100L, preferably 2 to 10L, more preferably 3 to 5L, relative to 1 mole of the compound represented by the formula (VIII);

in the step K), the amount of the catalyst tetrakistriphenylphosphine palladium may be 0.001 to 0.1 part by mass, preferably 0.005 to 0.03 part by mass, and more preferably 0.01 to 0.02 part by mass, relative to 1 part by mass of the compound represented by the formula (viii); the amount of sodium borohydride is 0.001-0.1 parts by mass, preferably 0.01-0.04 parts by mass, more preferably 0.03-0.04 parts by mass;

12. Use of a compound of the formula (i) or an agriculturally pharmaceutically acceptable salt according to claim 1 for controlling pests or for producing a formulation for controlling pests.

13. Use according to claim 12, characterized in that: pests include the following: lepidopteran, coleopteran, orthopteran, isopteran, rodentia, louse, mallophaga, thysanoptera, heteropteran, hemiptera, hymenopteran, dipteran, siphonaptera, thysanoptera and acarids, in particular from the orders acarina, dipteran, thysanoptera, lepidopteran and coleopteran;

or, the pest comprises mites comprising: tetranychid, goiter, tetranychid, tetranychus urticae;

or, the pest comprises a nematode, including nematodes of the following genera: cyst nematodes, heterodera, meloidogyne, radopholus, pratylenchus, strongyloides, trichinella, ceratodes, nematodiasis, ceratodes, stemodera, restylenchus, and eelworms.

14. Use according to claim 13, characterized in that: pests are pests which occur on plants, in particular on useful plants and ornamentals in agriculture, horticulture and forestry, or on parts of said plants;

the plant includes grain, beet, fruit, leguminous plant, oil plant, cucurbitaceae plant, fiber plant, vegetable, lauraceae plant, tobacco, nut, coffee, sugar cane, tea, pepper, hops, natural rubber plant and ornamental plant.

15. A pesticidal composition, the active ingredient of which comprises at least one compound of formula I as defined in claim 1.

16. The pesticide composition as set forth in claim 15, characterized in that: the pesticide composition also includes an agriculturally acceptable carrier.

17. The composition according to claim 15 or 16, characterized in that: the pesticide composition is prepared into any dosage form acceptable in the agricultural pharmacy, including missible oil, suspension concentrate, directly-sprayable or dilutable solution, coatable paste, dilute emulsion, wettable powder, soluble powder, dispersible powder, wettable powder, granules and polymer encapsulation.

18. A method of using the composition of any one of claims 15-17, comprising spraying, misting, dusting, coating, dressing, spreading or pouring.

19. Use according to claim 18, characterized in that: typical concentrations of the active ingredient when the composition is used are in the range of 0.l to 1000ppm, preferably 0.1 to 500 ppm; the amount per hectare is generally from l to 2000g of active ingredient per hectare, in particular from 10 to 1000g, preferably from 20 to 600 g; more preferably 20-100 g/ha.