Avermectin B2a/2b amine derivatives, derivative salts thereof, and preparation method and application of avermectin B2a/2b amine derivative salt

Abstract

The invention relates to avermectin B2a / 2b amine derivatives and derivative salts thereof, and a preparation method and an application of the avermectin B2a / 2b amine derivative salts. The avermectin B2a / 2b amine derivatives comprise six types of compounds. The avermectin B2a / 2b amine derivative salts are salts formed by reactions of the six types of avermectin B2a / 2b amine derivatives and organic acid and inorganic acid. The preparation method of the avermectin B2a / 2b amine derivative salts comprises the steps that: (1) avermectin B2a / 2b is subjected to a protective reaction with tert-butyl dimethyl chlorosilane or allyl chloroformate; (2) protected B2a / 2b is subjected to a reaction with an oxidant, such that an avermectin B2a / 2b ketone compound is obtained; (3) the ketone compound is subjected to an amination reaction, such that protected amine derivative is obtained; and (4) the protective agent is removed, such that B2a / 2b amine derivative is obtained; the derivative is subjected to a reaction with organic or inorganic acid, such that avermectin B2a / 2b amine derivative salt is obtained. According to the invention, avermectin B2 is adopted as a matrix for synthesizing avermectin B2a / 2b amine derivative and avermectin B2a / 2b amine derivative salt, such that avermectin B2 applciation range is widened.

Description

technical field

[0001] The invention belongs to the technical field of agricultural chemicals and their preparation, and relates to a kind of abamectin B 2a / 2b Amino derivatives and derivative salts, Abamectin B 2a / 2b Preparation method and application of amino derivative salt. Background technique

[0002] Avermectin is produced by Sterptomyces avermitills, which is a kind of streptomycin and belongs to streptomycin griseus. Abamectin is a mixture of fermentation components, a total of 8 components: A 1a 、A 1b 、A 2a 、A 2b , B 1a , B 1b , B 2a , B 2b . The abamectin exists in the mycelium of the fermented liquid, the filtrate is removed by filtration, the filter cake is extracted with a solvent, desugared, concentrated and crystallized to obtain the abamectin fine product.

[0003] Avermectin is a neurotoxin, its mechanism is to act on the GABAA receptors of insect neuron synapses or neuromuscular synapses, interfere with the information transmission of nerve endi...

Examples

example 1

[0038] Example 1 4"-deoxy-4"-methylamino abamectin B 2a / 2b Preparation of benzoate

[0039] 10g abamectin B 2a / 2b （ Content B 2a 93%, B 2b 3% ） Dissolve in 100ml dichloromethane, lower the temperature to -30°C, add 3.0g allyl acetate and 3.0g tetramethylethylenediamine, and react for 2 hours. The temperature was raised to -20°C and then 5.0 g of tetramethylethylene diamine, 5.0 g of dimethyl sulfoxide and 5.0 g of phenyl phosphate dichloride were added, and the reaction was carried out for 3 hours. Add 5% phosphoric acid solution and 10% sodium hydroxide solution respectively, adjust the pH value to 2 and then to 7-8, separate the layers, dry the organic phase with sodium sulfate, and remove the solvent under reduced pressure. The residue was dissolved in toluene, 10g heptamethyldisilazane and 1.0g zinc chloride were added, and the temperature was kept at 75°C for 6 hours. Start to cool down, add 10g ethanol, 2.0g sodium borohydride when the temperature is cooled to 0°C, keep...

example 2

[0040] Example 2 23-deoxy-23-methylaminoabamectin B 2a / 2b Preparation of phosphate

[0041] 10g Abamectin B 2a / 2b (Content B 2a 93%, B 2b 3%) Dissolve in 100m1 of dichloromethane, lower the temperature to -30°C, add 3.0g tert-butyldimethylchlorosilane and 3.0g tetramethylethylenediamine, and react for 2 hours. The temperature was raised to -20°C and 8.0 g of tetramethylethylene diamine, 8.0 g of dimethyl sulfoxide and 8.0 g of phenyl phosphate dichloride were added, and reacted for 3 hours. Add phosphoric acid solution and sodium hydroxide solution, adjust the pH to 2 and then to 7-8, separate the layers, dry the organic phase with sodium sulfate, and remove the solvent under reduced pressure.

[0042] The residue was dissolved in toluene, 10g heptamethyldisilazane and 1.0g zinc chloride were added, and the temperature was kept at 75°C for 6 hours. Start to cool down, add 10g ethanol, cool to 0°C, add 2.0g sodium borohydride, 1 hour later, add 10g ethanol, 0.005g tetrakistriphen...

example 3

[0043] Example 3 4",23-deoxy-4",23-bis(N-methylamino)abamectin B 2a / 2b Preparation of benzoate

[0044] 10g abamectin B 2a / 2b （ Content B 2a 93%, B 2b 3% ） Dissolve in 100ml dichloromethane, lower the temperature to -30°C, add 1.5g tert-butyldimethylchlorosilane and 1.0g tetramethylethylenediamine, and react for 2 hours. The temperature was raised to -20°C and 8.0 g of tetramethylethylene diamine, 8.0 g of dimethyl sulfoxide and 8.0 g of phenyl phosphate dichloride were added, and reacted for 3 hours. Add phosphoric acid solution and sodium hydroxide solution, first adjust the pH to 2 and then to 7-8, separate the layers, dry with sodium sulfate, and remove the solvent from the organic phase under reduced pressure.

[0045] The residue was dissolved in toluene, 15g heptamethyldisilazane and 1.5g zinc chloride were added, and the temperature was kept at 75°C for 6 hours. Start to cool down, add 10g ethanol, add 4.0g sodium borohydride and keep it for 1 hour when the temperature ...

technical field

[0001] The invention belongs to the technical field of agricultural chemicals and their preparation, and relates to a kind of abamectin B 2a / 2b Amino derivatives and derivative salts, Abamectin B 2a / 2b Preparation method and application of amino derivative salt. Background technique

[0002] Avermectin is produced by Sterptomyces avermitills, which is a kind of streptomycin and belongs to streptomycin griseus. Abamectin is a mixture of fermentation components, a total of 8 components: A 1a 、A 1b 、A 2a 、A 2b , B 1a , B 1b , B 2a , B 2b . The abamectin exists in the mycelium of the fermented liquid, the filtrate is removed by filtration, the filter cake is extracted with a solvent, desugared, concentrated and crystallized to obtain the abamectin fine product.

[0003] Avermectin is a neurotoxin, its mechanism is to act on the GABAA receptors of insect neuron synapses or neuromuscular synapses, interfere with the information transmission of nerve endi...

Examples

example 1

[0038] Example 1 4"-deoxy-4"-methylamino abamectin B 2a / 2b Preparation of benzoate

[0039] 10g abamectin B 2a / 2b （ Content B 2a 93%, B 2b 3% ） Dissolve in 100ml dichloromethane, lower the temperature to -30°C, add 3.0g allyl acetate and 3.0g tetramethylethylenediamine, and react for 2 hours. The temperature was raised to -20°C and then 5.0 g of tetramethylethylene diamine, 5.0 g of dimethyl sulfoxide and 5.0 g of phenyl phosphate dichloride were added, and the reaction was carried out for 3 hours. Add 5% phosphoric acid solution and 10% sodium hydroxide solution respectively, adjust the pH value to 2 and then to 7-8, separate the layers, dry the organic phase with sodium sulfate, and remove the solvent under reduced pressure. The residue was dissolved in toluene, 10g heptamethyldisilazane and 1.0g zinc chloride were added, and the temperature was kept at 75°C for 6 hours. Start to cool down, add 10g ethanol, 2.0g sodium borohydride when the temperature is cooled to 0°C, keep...

example 2

[0040] Example 2 23-deoxy-23-methylaminoabamectin B 2a / 2b Preparation of phosphate

[0041] 10g Abamectin B 2a / 2b (Content B 2a 93%, B 2b 3%) Dissolve in 100m1 of dichloromethane, lower the temperature to -30°C, add 3.0g tert-butyldimethylchlorosilane and 3.0g tetramethylethylenediamine, and react for 2 hours. The temperature was raised to -20°C and 8.0 g of tetramethylethylene diamine, 8.0 g of dimethyl sulfoxide and 8.0 g of phenyl phosphate dichloride were added, and reacted for 3 hours. Add phosphoric acid solution and sodium hydroxide solution, adjust the pH to 2 and then to 7-8, separate the layers, dry the organic phase with sodium sulfate, and remove the solvent under reduced pressure.

[0042] The residue was dissolved in toluene, 10g heptamethyldisilazane and 1.0g zinc chloride were added, and the temperature was kept at 75°C for 6 hours. Start to cool down, add 10g ethanol, cool to 0°C, add 2.0g sodium borohydride, 1 hour later, add 10g ethanol, 0.005g tetrakistriphen...

example 3

[0043] Example 3 4",23-deoxy-4",23-bis(N-methylamino)abamectin B 2a / 2b Preparation of benzoate

[0044] 10g abamectin B 2a / 2b （ Content B 2a 93%, B 2b 3% ） Dissolve in 100ml dichloromethane, lower the temperature to -30°C, add 1.5g tert-butyldimethylchlorosilane and 1.0g tetramethylethylenediamine, and react for 2 hours. The temperature was raised to -20°C and 8.0 g of tetramethylethylene diamine, 8.0 g of dimethyl sulfoxide and 8.0 g of phenyl phosphate dichloride were added, and reacted for 3 hours. Add phosphoric acid solution and sodium hydroxide solution, first adjust the pH to 2 and then to 7-8, separate the layers, dry with sodium sulfate, and remove the solvent from the organic phase under reduced pressure.

[0045] The residue was dissolved in toluene, 15g heptamethyldisilazane and 1.5g zinc chloride were added, and the temperature was kept at 75°C for 6 hours. Start to cool down, add 10g ethanol, add 4.0g sodium borohydride and keep it for 1 hour when the temperature ...

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