CN111518154B - Preparation method of 24-epibrassinol intermediate (22E, 24R) -3 alpha, 5-ring-5 alpha-ergosta-7, 22-diene-6-ketone - Google Patents
Preparation method of 24-epibrassinol intermediate (22E, 24R) -3 alpha, 5-ring-5 alpha-ergosta-7, 22-diene-6-ketone Download PDFInfo
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Abstract
The invention discloses a preparation method of a 24-epibrassinone intermediate (22E, 24R) -3 alpha, 5-ring-5 alpha-ergosta-7, 22-diene-6-ketone, which comprises the following steps: 1) ergosterol is used as a starting material, and is subjected to mesylation under the catalysis of tetrabutylammonium hydrogen sulfate to obtain a first-step product, namely an intermediate 1, a first-step reaction solution is filtered, and a filtrate is directly subjected to a next-step reaction; 2) adding water and potassium bicarbonate into the filtrate obtained in the first step of reaction, heating for reaction, carrying out phase separation to remove water, concentrating, cooling, and filtering to obtain an intermediate 2; 3) the intermediate 2 reacts with benzyl halide in the presence of an acid-binding agent to generate an etherification product; 4) the etherification product reacts with tetrabutylammonium bromide and tetrabutylammonium hydrogen persulfate to prepare an intermediate 3. With conventional CrO3Compared with the pyridine oxidation method, the method avoids using the oxidant containing heavy metal chromium which seriously pollutes the environment, and also has the advantages of mild reaction conditions, high yield, simple post-treatment, capability of carrying out the next reaction without refining and the like.
Description
Technical Field
The invention belongs to the technical field of preparation of plant growth regulators, and particularly relates to a preparation method of a 24-epibrassinol intermediate (22E, 24R) -3 alpha, 5-cyclo-5 alpha-ergosta-7, 22-diene-6-ketone.
Background
24-epibrassinolide is a broad-spectrum and highly efficient plant growth regulator, which was earlier discovered by American agricultural scientists in 1970 and is named as brassinolide, also known as 24-epibrassinolide. The 24-epibrassinolide is different from other plant growth regulators in unidirectional pertinence in promoting crop yield increase and improving quality. Not only has the physiological functions of auxin and cytokinin, but also has the functions of improving photosynthesis, regulating nutrition distribution, promoting the transportation of stem leaf carbohydrate to granules, improving the stress resistance of crops to external adverse factors, promoting the growth capacity of weak parts of plants and the like, so that the fertilizer has extremely wide usability and practicability.
The traditional preparation method of 24-epibrassinol intermediate (comprising intermediate 1, intermediate 2 and intermediate 3) comprises the following steps:
(1) in 1979, Thompson et al (Thompson m.j., Mandava, n., Flippen-Anderson j.l., et al.j.org.chem,1979,26,5002.) proposed a total synthesis of 24-epibrassinol. Ergosterol is used as an initial raw material and undergoes nine steps of sulfonylation, hydrolysis, oxidation, reduction, rearrangement, sulfonylation, elimination, dihydroxylation and ring expansion to obtain 24-epibrassinol. Because the steps are long, the total yield is low, and the preparation of the intermediate 3 adopts a chromium trioxide/pyridine oxidation system, a large amount of waste liquid and solid waste containing heavy metal ions can be generated, and the environmental pollution is serious;
(2) McMorris et al, 1993, improved a method for synthesizing 24-epibrassinol (McMorris T.C., Patil, J.org.chem.1993,58,2338.) and shortened the synthesis steps to seven steps, but the chromium trioxide/pyridine oxidation system is still used for preparing the intermediate 3, which results in the generation of a large amount of waste liquid and solid waste containing heavy metal ions and serious environmental pollution;
(3) jiangfenfeng et al 2010 (CN 101812114A) prepared intermediate 3 using an osmium tetroxide/m-chloroperoxybenzoic acid oxidation system. Osmium tetroxide is a volatile highly toxic solid powder, and is expensive, high in cost and high in requirement on operators.
(4) Zhou Fu Rong et al 2019 (CN 111004303A) adopt manganese dioxide/air system to prepare intermediate 3, and methanol is used as solvent, and air is introduced for oxidation. Although manganese dioxide can be recycled after being calcined, a large amount of methanol gas can be released due to the need of introducing air, and the accumulated methanol gas can reach the explosion limit, so that certain potential safety hazards exist;
in recent years, some novel oxidation methods have appeared, and the method has the advantages of mild reaction conditions, high yield, simple and convenient post-treatment and the like. For example, Moriyama, K. et al (Moriyama, K., Nakamura, Y., Togo, H. (2014). Organic Letters,16(14), 3812-3815.) report that certain compounds having an ether structure can be used to obtain ketone compounds in acetonitrile solvent under the action of potassium bromide and potassium monopersulfate (Oxone) with a yield of 99%.
Referring to the method of Moriyama, K.et al, the intermediate 2 is used as a raw material, and is reacted with benzyl chloride to prepare an ether compound, and then the ketone compound is synthesized under the action of potassium bromide and potassium monopersulfate.
It is possible that the poor solubility of potassium bromide and potassium monopersulfate in ether acetonitrile makes it difficult for bromide and potassium monopersulfate to enter the solution effectively to participate in the reaction. To verify this hypothesis, tetrabutylammonium bromide (TBAB) was used instead of potassium bromide, tetrabutylammonium hydrogen persulfate (n-Bu)4NHSO5Or TBAOX) instead of oxone. Wherein, tetrabutylammonium bromide and tetrabutylammonium hydrogen persulfate belong to oil and water soluble substances, and have the function of a phase transfer catalyst, so that the dissolution of ether in acetonitrile can be promoted. Surprisingly, the reaction time is shortened to 1h from 24h reported in the literature under the action of tetrabutylammonium bromide and tetrabutylammonium hydrogen persulfate, and the yield can reach 70.6%. Whereas when using potassium bromide + TBAOX or TBAB + Oxone combinations, the reaction conversion is slow. It is well established that the solubility of potassium bromide and potassium monopersulfate has a critical effect on the reaction.
Disclosure of Invention
The invention provides a preparation method of a 24-epibrassinol intermediate (22E, 24R) -3 alpha, 5-cyclo-5 alpha-ergosta-7, 22-diene-6-ketone, aiming at improving the defects of low yield, heavy metal pollution, need of column chromatography purification of reaction products and the like in the existing method.
The purpose of the invention is realized as follows:
a preparation method of a 24-epibrassinol intermediate (22E, 24R) -3 alpha, 5-ring-5 alpha-ergosta-7, 22-diene-6-ketone takes ergosterol as a starting material and adopts a four-step synthesis method comprising mesylation, hydrolysis, etherification and oxidation reactions, and is characterized by comprising the following steps:
1) mesylation reaction: adding ergosterol, acetone and tetrabutylammonium hydrogen sulfate into a reaction bottle, stirring for 0.5h, cooling to-5 ℃ by using brine ice, adding methanesulfonyl chloride, dropwise adding an acid binding agent at-5 ℃, dropwise adding for 0.5h, continuing to perform heat preservation reaction at-5 ℃ for 2-4 h after dropwise adding is finished, obtaining an intermediate 1 after the reaction is finished, and filtering the reaction solution to obtain white filtrate and light yellow filtrate containing the intermediate 1;
2) and (3) hydrolysis reaction: adding water and potassium bicarbonate into the light yellow filtrate containing the intermediate 1 obtained in the step 1), stirring, heating to 50-60 ℃, keeping the temperature, reacting for 2-5 hours, keeping the temperature, stopping stirring, carrying out phase separation, separating out a lower-layer water phase, keeping an upper-layer organic phase, concentrating the organic phase to half volume, cooling to-10-0 ℃, separating out solids, filtering, and drying to obtain light yellow powder, namely the intermediate 2;
3) and (3) etherification reaction: dissolving the intermediate 2 obtained in the step 2) in a solvent, cooling to-5 ℃ under stirring, adding 60% sodium hydride, keeping the temperature and stirring for 10-30 min after adding, dropwise adding benzyl halide at-5 ℃, keeping the temperature and reacting for 24-48 h at 0-30 ℃ after dropwise adding, adding water to quench the reaction after the reaction is finished, dropwise adding hydrochloric acid to adjust the pH to 7, extracting with an organic solvent, separating out a water layer, washing the organic layer once, separating out the water layer, and concentrating the organic layer to obtain a light yellow oily substance, namely an etherified product;
4) and (3) oxidation reaction: dissolving the etherification product obtained in the step 3) in a solvent, cooling to-5 ℃, adding tetrabutylammonium bromide and tetrabutylammonium hydrogen persulfate, stirring at 0-30 ℃ for 1-6 h, adding water to quench the reaction after the reaction is finished, filtering to obtain light yellow filter solids, pulping the filter solids with water, and performing suction filtration to obtain white solids, namely an intermediate 3;
in the step 1), the molar ratio of ergosterol to tetrabutylammonium hydrogen sulfate is 1: 0.05-0.5, the molar ratio of ergosterol to methanesulfonyl chloride is 1: 1-3, the acid-binding agent is triethylamine, the molar ratio of ergosterol to triethylamine is 1: 1-3, and the mass ratio of ergosterol to acetone is 1: 8-10.
In the step 2), the molar ratio of the potassium bicarbonate to the intermediate 1 is 1.3-3: 1, and the mass ratio of the intermediate 1 to the water is 1: 0.8-1.6.
In the step 3), the solvent is tetrahydrofuran or N, N-dimethylformamide, and the mass ratio of the intermediate 2 to the tetrahydrofuran or the N, N-dimethylformamide is 1: 10-16.
In the step 3), the molar ratio of the 60% sodium hydride to the intermediate 2 is 2.5-5: 1, and stirring is carried out for 30min under the condition of heat preservation.
In the step 3), the benzyl halide is benzyl chloride, benzyl bromide or benzyl iodide, and the molar ratio of the benzyl halide to the intermediate 2 is 1-2: 1.
In the step 3), the mass ratio of the intermediate 2 to the quenching water is 1: 9-17.5; the mass fraction of the solute of the hydrochloric acid solution is 5%.
In the step 3), the organic solvent for extraction is ethyl acetate or ethyl ether, and the mass ratio of the intermediate 2 to the ethyl acetate or the ethyl ether is 1: 9-17.5.
In the step 4), the solvent is acetonitrile, and the mass ratio of the etherification product to the acetonitrile is 1: 8.8-14.5; adding water for quenching after the reaction is finished, wherein the mass ratio of the etherification product to quenching water is 1: 8.8-14.5; and pulping the filter solids by using water, wherein the mass ratio of the etherification product to the water is 1: 7.3-14.5.
In the step 4), the molar ratio of tetrabutylammonium bromide to the etherification product is 1-3: 1, and the molar ratio of tetrabutylammonium hydrogen persulfate to the etherification product is 1-3: 1.
In the step 4), the preparation method of tetrabutylammonium hydrogen persulfate refers to the method reported by Benjamin R et al (Benjamin R. travis, Benjamin P. Ciaramitaro, Babak Borhan. Eur. J. org. chem.2002, 3429-3434.).
The invention has the following beneficial effects:
(1) in the first step of the reaction, acetone is used as a solvent, and although the solubility of ergosterol in acetone is poor, the solubility is obviously improved after the phase transfer catalyst tetrabutylammonium bromide is added. After the first-step reaction is finished, only insoluble salt is filtered to remove, and the filtrate containing the intermediate 1 can be subjected to the next-step reaction without considering further post-treatment;
(2) the filtrate obtained in the first step is used for the reaction in the second step, after the reaction is finished, the water phase is removed through phase separation, the organic phase is concentrated to separate out solid, and the intermediate 2 can be obtained through filtration and can be used for the reaction in the third step after drying without further purification;
(3) in the third step of reaction, the reaction conditions are mild, and the reaction is carried out at the temperature of 0-30 ℃. The post-treatment is simple, and the etherified product can be directly applied to the next reaction after extraction and concentration without further purification;
(4) in the fourth step of reaction, the reaction rate is high, the post-treatment is simple, and the intermediate 3 is pulped by water to obtain a high-content product without column chromatography purification.
Drawings
FIG. 1 is a process flow diagram of a method of preparing a 24-epibrassinol intermediate of the invention.
FIG. 2 is a liquid phase diagram of a pure 24-epibrassinol intermediate 3 prepared in example 1.
FIG. 3 is a nuclear magnetic hydrogen spectrum of the pure 24-epibrassinol intermediate 3 prepared in example 1.
Detailed Description
The invention is further illustrated, but not limited, by the following examples in connection with the accompanying drawings.
Example 1
A process for the preparation of the 24-epibrassinol intermediate (22E, 24R) -3 α, 5-cyclo-5 α -ergosta-7, 22-dien-6-one comprising the steps of:
1) adding 100.0g of ergosterol, 800.0g of acetone and 4.3g of tetrabutylammonium hydrogen sulfate into a reaction bottle, stirring for 0.5h, cooling to-5 ℃ by using brine ice, adding 29.0g of methanesulfonyl chloride, dropwise adding 25.5g of triethylamine at-5 ℃, dropwise adding for 0.5h, continuing to perform heat preservation reaction at-5 ℃ for 4h after dropwise adding is finished, obtaining an intermediate 1 after the reaction is finished, and filtering the reaction solution to obtain white filtrate and light yellow filtrate containing the intermediate 1;
2) adding 200g of water and 32.8g of potassium bicarbonate into the light yellow filtrate containing the intermediate 1 obtained in the step 1), stirring, heating to 50 ℃, keeping the temperature, reacting for 5 hours, after the reaction is finished, stopping stirring while keeping the temperature, carrying out phase separation, separating out a lower-layer water phase, retaining an upper-layer organic phase, concentrating the organic phase to half volume, cooling to-10-0 ℃, separating out solids, filtering, and drying to obtain 110.3g of light yellow powdery intermediate 2;
3) dissolving 110.3g of the intermediate 2 obtained in the step 2) in 1000.0g of tetrahydrofuran, cooling to-5 ℃ under stirring, adding 15.2g of 60% sodium hydride in batches, stirring at a constant temperature for 30min after adding, dropwise adding 32.0g of benzyl chloride at-5 ℃, reacting at 0 ℃ for 48h after dropwise adding, adding water to quench the reaction after the reaction is finished, dropwise adding 5% hydrochloric acid to adjust the pH to 7, extracting with 1000g of ethyl acetate, separating a water layer, washing the organic layer with water once, separating the water layer, and concentrating the organic layer to obtain 136.6g of light yellow oily substance, namely an etherified product;
4) dissolving the etherification product obtained in the step 3) in 1200.0g of acetonitrile, cooling to-5 ℃, adding 81.3g of tetrabutylammonium bromide and 89.8g of tetrabutylammonium hydrogen persulfate, stirring at 0 ℃ for 6h, adding 1200g of water to quench and react after the reaction is finished, filtering to obtain light yellow filter solids, pulping the filter solids with 1000.0g of water, and performing suction filtration to obtain white solids, namely an intermediate 3, and drying at 70-80 ℃ under negative pressure to obtain 70.9g of white powdery solids, namely a pure 24-epibrassinol intermediate 3 product.
As can be seen from FIG. 3, nuclear magnetic hydrogen spectrum data of pure 24-epibrassin intermediate 31H NMR(450MHz,CDCl3),0.68(s,3H,-CH3),0.82-0.85(t,6H,-CH3),0.92(d,3H,-CH3),1.04(d,3H,-CH3),1.09(s,3H,-CH3),5.14-5.28(m,2H,-C＝CH),5.79-5.80(t,1H,-C＝CH)。
As can be seen from FIG. 2, the pure 24-epibrassinomin intermediate 3 obtained above has a content of 95.0% and a total yield of 67.7% in four steps, as determined by liquid phase detection.
Example 2
A process for the preparation of the 24-epibrassinol intermediate (22E, 24R) -3 α, 5-cyclo-5 α -ergosta-7, 22-dien-6-one comprising the steps of:
1) adding 100.0g of ergosterol, 900.0g of acetone and 8.6g of tetrabutylammonium hydrogen sulfate into a reaction bottle, stirring for 0.5h, cooling to-5 ℃ by using brine ice, adding 58.0g of methanesulfonyl chloride, dropwise adding 51.0g of triethylamine at-5 ℃, dropwise adding for 0.5h, continuing to perform heat preservation reaction at-5 ℃ for 3h after dropwise adding is finished, obtaining an intermediate 1 after the reaction is finished, and filtering the reaction solution to obtain white filtrate and light yellow filtrate containing the intermediate 1;
2) adding 150g of water and 50.0g of potassium bicarbonate into the light yellow filtrate containing the intermediate 1 obtained in the step 1), stirring, heating to 55 ℃, keeping the temperature for reaction for 3 hours, stopping stirring while keeping the temperature after the reaction is finished, carrying out phase separation, separating out a lower-layer water phase, retaining an upper-layer organic phase, concentrating the organic phase to a half volume, cooling to-10-0 ℃, separating out solids, filtering, and drying to obtain 115.0g of light yellow powdery intermediate 2;
3) dissolving 115.0g of the intermediate 2 obtained in the step 2) in 1300.0g of tetrahydrofuran, cooling to-5 ℃ under stirring, adding 20.3g of 60% sodium hydride in batches, stirring at a constant temperature for 30min after adding, dropwise adding 48.0g of benzyl chloride at-5 ℃, reacting at 10 ℃ for 36h after dropwise adding, adding 1300g of water after the reaction is finished, quenching, dropwise adding 5% hydrochloric acid to adjust the pH to be 7, extracting with 1500g of diethyl ether, separating a water layer, washing an organic layer once with water, separating a water layer, and concentrating the organic layer to obtain 135.0g of light yellow oily matter, namely an etherified product;
4) dissolving the etherification product obtained in the step 3) in 1500.0g of acetonitrile, cooling to-5 ℃, adding 162.6g of tetrabutylammonium bromide and 180.0g of tetrabutylammonium hydrogen persulfate, stirring for 4 hours at 20 ℃, adding 1500.0g of water to quench and react after the reaction is finished, filtering to obtain light yellow filter solids, pulping the filter solids with 1500.0g of water, and performing suction filtration to obtain white solids, namely an intermediate 3, and drying at 70-80 ℃ under negative pressure to obtain 72.0g of white powdery solids, namely a pure 24-epi-brassinon intermediate 3.
The content of the pure 24-epi-brassinomin intermediate 3 product is 96.0 percent through liquid phase detection, and the total yield of the four steps is 69.5 percent.
Example 3
A process for the preparation of the 24-epibrassinol intermediate (22E, 24R) -3 α, 5-cyclo-5 α -ergosta-7, 22-dien-6-one comprising the steps of:
1) adding 100.0g of ergosterol, 1000.0g of acetone and 43.0g of tetrabutylammonium hydrogen sulfate into a reaction bottle, stirring for 0.5h, cooling to-5 ℃ with brine ice, adding 87.0g of methanesulfonyl chloride, dropwise adding 76.5g of triethylamine at-5 ℃, dropwise adding for 0.5h, continuing to perform heat preservation reaction at-5 ℃ for 2h after dropwise adding is finished, obtaining an intermediate 1 after the reaction is finished, and filtering the reaction solution to obtain white filtrate and light yellow filtrate containing the intermediate 1;
2) adding 100g of water and 75.0g of potassium bicarbonate into the light yellow filtrate containing the intermediate 1 obtained in the step 1), stirring, heating to 60 ℃, keeping the temperature for reaction for 2 hours, stopping stirring while keeping the temperature after the reaction is finished, carrying out phase separation, separating out a lower-layer water phase, retaining an upper-layer organic phase, concentrating the organic phase to half volume, cooling to-10-0 ℃, separating out solids, filtering, and drying to obtain 114.0g of light yellow powdery intermediate 2;
3) dissolving 114.0g of the intermediate 2 obtained in the step 2) in 1600.0g of N, N-dimethylformamide, cooling to-5 ℃ under stirring, adding 30.5g of 60% sodium hydride in batches, keeping the temperature and stirring for 30min after adding, dropwise adding 64.0g of benzyl chloride at-5 ℃, keeping the temperature and reacting for 24h at 30 ℃ after dropwise adding, adding 1600.0g of water after the reaction is finished, quenching the reaction, dropwise adding 5% hydrochloric acid to adjust the pH value to be 7, extracting with 2000g of ethyl acetate, separating out a water layer, washing an organic layer once, separating out the water layer, and concentrating the organic layer to obtain 138.0g of a light yellow oily substance, namely an etherified product;
4) dissolving the etherification product obtained in the step 3) in 2000.0g of acetonitrile, cooling to-5 ℃, adding 243.9g of tetrabutylammonium bromide and 270.0g of tetrabutylammonium hydrogen persulfate, stirring at 30 ℃ for 1h, adding 2000.0g of water to quench and react after the reaction is finished, filtering to obtain light yellow filter solids, pulping the filter solids with 2000.0g of water, and performing suction filtration to obtain white solids, namely an intermediate 3, and drying at 70-80 ℃ under negative pressure to obtain 74.0g of white powdery solids, namely a pure 24-epibrassinol intermediate 3.
The pure product of the 24-epibrassinon intermediate 3 obtained by the method is detected by a liquid phase, the content is 95.0 percent, and the total yield of the four steps is 70.6 percent.
The reaction sequence of examples 1-3 is as follows:
as can be seen from the test data of examples 1 to 3, compared with the prior art, the preparation method of examples 1 to 3 not only improves the yield of the 24-epibrassinol intermediate 3, but also shortens the reaction time and improves the production efficiency; the invention uses acetone as the reaction solvent of the first step, thereby simplifying the post-treatment operation. Although the etherification reaction is introduced, the use of an oxidant containing heavy metal chromium ions which seriously pollutes the environment is avoided, the post-treatment process is simple, the high-content 24-epibrassinol intermediate 3 can be obtained only by pulping with water, column chromatography purification is not needed, and the production efficiency is greatly improved.
Finally, it should be noted that: although the present invention has been described in detail with reference to the foregoing embodiments, it will be apparent to those skilled in the art that modifications may be made to the embodiments or portions thereof without departing from the spirit and scope of the invention.
Claims (10)
1. A preparation method of a 24-epibrassinol intermediate (22E, 24R) -3 alpha, 5-ring-5 alpha-ergosta-7, 22-diene-6-ketone takes ergosterol as a starting material and adopts a four-step synthesis method comprising mesylation, hydrolysis, etherification and oxidation reactions, and is characterized by comprising the following steps:
1) mesylation reaction: adding ergosterol, acetone and tetrabutylammonium hydrogen sulfate into a reaction bottle, stirring for 0.5h, cooling to-5 ℃ by using brine ice, adding methanesulfonyl chloride, dropwise adding an acid binding agent at-5 ℃, dropwise adding for 0.5h, continuing to perform heat preservation reaction at-5 ℃ for 2-4 h after dropwise adding is finished, obtaining an intermediate 1 after the reaction is finished, and filtering the reaction solution to obtain white filtrate and light yellow filtrate containing the intermediate 1;
2) and (3) hydrolysis reaction: adding water and potassium bicarbonate into the light yellow filtrate containing the intermediate 1 obtained in the step 1), stirring, heating to 50-60 ℃, keeping the temperature, reacting for 2-5 hours, keeping the temperature, stopping stirring, carrying out phase separation, separating out a lower-layer water phase, keeping an upper-layer organic phase, concentrating the organic phase to half volume, cooling to-10-0 ℃, separating out solids, filtering, and drying to obtain light yellow powder, namely the intermediate 2;
3) and (3) etherification reaction: dissolving the intermediate 2 obtained in the step 2) in a solvent, cooling to-5 ℃ under stirring, adding 60% sodium hydride, keeping the temperature and stirring for 10-30 min after adding, dropwise adding benzyl halide at-5 ℃, keeping the temperature and reacting for 24-48 h at 0-30 ℃ after dropwise adding, adding water to quench the reaction after the reaction is finished, dropwise adding hydrochloric acid to adjust the pH to 7, extracting with an organic solvent, separating out a water layer, washing the organic layer once, separating out the water layer, and concentrating the organic layer to obtain a light yellow oily substance, namely an etherified product;
4) and (3) oxidation reaction: dissolving the etherification product obtained in the step 3) in a solvent, cooling to-5 ℃, and adding tetrabutylammonium bromide and tetrabutylammonium hydrogen persulfate (n-Bu)4NHSO5Or TBAOX), stirring for 1-6 h at 0-30 ℃, adding water to quench and react after the reaction is finished, filtering to obtain light yellow filter solids, pulping the filter solids with water, and performing suction filtration to obtain white solids, namely the intermediate 3;
2. the method for preparing the 24-epi-brassinolide intermediate (22E, 24R) -3 α, 5-cyclo-5 α -ergosta-7, 22-dien-6-one according to claim 1, wherein in the step 1), the molar ratio of ergosterol to tetrabutylammonium hydrogen sulfate is 1: 0.05-0.5, the molar ratio of ergosterol to methanesulfonyl chloride is 1: 1-3, the acid-binding agent is triethylamine, the molar ratio of ergosterol to triethylamine is 1: 1-3, and the mass ratio of ergosterol to acetone is 1: 8-10.
3. The method for producing a 24-epibrassinolide intermediate (22E, 24R) -3 α, 5-cyclo-5 α -ergosta-7, 22-dien-6-one according to claim 1, wherein in the step 2), the molar ratio of potassium bicarbonate to intermediate 1 is 1.3 to 3:1, and the mass ratio of intermediate 1 to water is 1:0.8 to 1.6.
4. The method for producing the 24-epibrassinolide intermediate (22E, 24R) -3 α, 5-cyclo-5 α -ergosta-7, 22-dien-6-one according to claim 1, wherein in the step 3), the solvent is tetrahydrofuran or N, N-dimethylformamide, and the mass ratio of the intermediate 2 to the tetrahydrofuran or the N, N-dimethylformamide is 1:10 to 16.
5. The method for preparing 24-epibrassinolide intermediate (22E, 24R) -3 α, 5-cyclo-5 α -ergosta-7, 22-dien-6-one according to claim 1, wherein in the step 3), the molar ratio of 60% sodium hydride to the intermediate 2 is 2.5-5: 1, and the mixture is stirred for 30min under heat preservation.
6. The method for preparing 24-epibrassinolide intermediate (22E, 24R) -3 α, 5-cyclo-5 α -ergosta-7, 22-dien-6-one according to claim 1, wherein in step 3), the benzyl halide is benzyl chloride, benzyl bromide or benzyl iodide, and the molar ratio of benzyl halide to intermediate 2 is 1-2: 1.
7. The method for producing a 24-epibrassinolide intermediate (22E, 24R) -3 α, 5-cyclo-5 α -ergosta-7, 22-dien-6-one according to claim 1, wherein in the step 3), the mass ratio of the intermediate 2 to the water for quenching is 1:9 to 17.5; the mass fraction of the solute of the hydrochloric acid solution is 5%.
8. The method for preparing 24-epibrassinolide intermediate (22E, 24R) -3 α, 5-cyclo-5 α -ergosta-7, 22-dien-6-one according to claim 1, wherein the organic solvent used for extraction in step 3) is ethyl acetate or diethyl ether, and the mass ratio of the intermediate 2 to the ethyl acetate or the diethyl ether is 1: 9-17.5.
9. The method for preparing the 24-epibrassinolide intermediate (22E, 24R) -3 α, 5-cyclo-5 α -ergosta-7, 22-dien-6-one according to claim 1, wherein in the step 4), the solvent is acetonitrile, and the mass ratio of the etherification product to the acetonitrile is 1: 8.8-14.5; adding water for quenching after the reaction is finished, wherein the mass ratio of the etherification product to quenching water is 1: 8.8-14.5; pulping the filter solids by using water, wherein the mass ratio of the water to the etherification product is 1: 7.3-14.5.
10. The method for preparing the 24-epibrassinolide intermediate (22E, 24R) -3 α, 5-cyclo-5 α -ergosta-7, 22-dien-6-one according to claim 1, wherein in the step 4), the molar ratio of tetrabutylammonium bromide to the etherification product is 1-3: 1, and the molar ratio of tetrabutylammonium hydrogen persulfate to the etherification product is 1-3: 1.
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| CN101812114A (en) * | 2010-05-14 | 2010-08-25 | 上海威敌生化(南昌)有限公司 | Preparation method of 24-epibrassinolide |
| CN102659913A (en) * | 2012-04-20 | 2012-09-12 | 吴中兴 | Reductive composition for preparing 24-epibrassinolide |
| CN111004303A (en) * | 2019-12-17 | 2020-04-14 | 京博农化科技有限公司 | Method for synthesizing 24-epibrassinolide |
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| CN102659913A (en) * | 2012-04-20 | 2012-09-12 | 吴中兴 | Reductive composition for preparing 24-epibrassinolide |
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