CN108752409B - Method for preparing epiandrostone with androstenedione as raw material - Google Patents

Method for preparing epiandrostone with androstenedione as raw material Download PDF

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CN108752409B
CN108752409B CN201810754782.6A CN201810754782A CN108752409B CN 108752409 B CN108752409 B CN 108752409B CN 201810754782 A CN201810754782 A CN 201810754782A CN 108752409 B CN108752409 B CN 108752409B
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androstenedione
epiandrosterone
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肖春桥
池汝安
陶琪
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Hubei Wudang Antai Pharmaceutical Co ltd
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Wuhan Institute of Technology
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J1/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, not substituted in position 17 beta by a carbon atom, e.g. estrane, androstane
    • C07J1/0003—Androstane derivatives
    • C07J1/0011—Androstane derivatives substituted in position 17 by a keto group

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Abstract

本发明涉及一种以雄烯二酮为原料制备表雄酮的方法，雄烯二酮经过3‑羰基烯酯化反应、17‑羰基缩酮保护反应、水解及钯碳催化还原反应、酸性水解反应等四步反应得到了目标产物表雄酮。与现有合成方法相比，该方法原料来源丰富、价格便宜、合成条件温和、催化剂还原效果好、产率高、生产成本较低，适合工业化生产。The invention relates to a method for preparing epiandrostone by using androstenedione as a raw material. The target product epiandrosterone is obtained by four-step reaction including reaction. Compared with the existing synthesis method, the method has abundant raw material sources, low price, mild synthesis conditions, good catalyst reduction effect, high yield and low production cost, and is suitable for industrial production.

Description

Method for preparing epiandrosterone by using androstenedione as raw material
Technical Field
The invention relates to the technical field of synthesis of medical intermediates, in particular to a novel method for preparing epiandrosterone by taking androstenedione as a raw material.
Background
The epiandrosterone serving as a steroid hormone intermediate can be used for synthesizing high-end androgenic hormone medicaments such as rocuronium bromide, vecuronium bromide and the like, can also be used as an additive of a cosmetic product, has the effects of resisting cancer, resisting aging, beautifying and the like, has a wide prospect in industry, and has the following structural formula:
Figure GDA0001787860640000011
the traditional synthetic method of epiandrosterone is to take diosgenin as a raw material, obtain Dehydroepiandrosterone (DHEA) by carrying out esterification, cracking, oxidation and hydrolysis on diketene acetate (diene for short, noted as II), carrying out oximation, back man rearrangement and hydrolysis on the diene, and finally obtaining epiandrosterone by carrying out hydrogenation reduction on the DHEA, wherein the synthetic route is as follows:
Figure GDA0001787860640000012
however, the traditional synthesis method has the problems of long route, complex process, low yield and the like, and the turmeric which is used as the raw material for synthesizing steroid hormone is limited by factors such as locality, seasonality and the like, and is influenced by over-development in recent years, so that the turmeric which is used as the raw material for synthesizing the steroid hormone intermediate is far from meeting the requirement of industrial production.
Chinese patent CN 103102379B discloses a method for preparing epiandrosterone by using monoalcohol ketoacetate as raw material and through oximation, back man rearrangement and hydrolysis, wherein the reaction equation is as follows:
Figure GDA0001787860640000021
however, due to the increasing exhaustion of turmeric which is a raw material for producing monoenes in recent years, the price of the monoenol ketone acetate is increasing, and the production cost is relatively high. In addition, the above method uses toxic reagent POCl3The method has higher potential safety production hazard and is not beneficial to safety production.
Chinese patent CN 105801649A discloses a method for obtaining epiandrosterone by using androstenedione as a raw material and selectively reducing androstenedione with a titanium dioxide composite catalyst. However, due to the simultaneous presence of 3 and 17 carbonyl groups in the androstenedione structure, the selective reduction effect is poor, resulting in relatively poor yields of epiandrosterone.
Chinese patent CN 105503985A discloses that epiandrosterone is prepared from androstenedione as raw material by esterification, ketal protection, ester decomposition, lithium-ammonia reduction, borohydride reduction and hydrolysis. However, in the method, two reduction reactions, namely lithium ammonia reduction reaction and borohydride reduction hydrolysis reaction, are adopted in the reaction process, the reaction process is complex, and the product yield is relatively low. The specific synthetic route of the method is as follows:
Figure GDA0001787860640000031
the invention aims to overcome the problems of the existing epiandrosterone synthesis method, and the palladium-carbon catalytic reduction reaction is used for replacing the existing complex lithium ammonia and boron hydrogen reduction reaction, so that the synthesis route is optimized, the process complexity is reduced, the product yield is improved, the production cost is reduced, and the method has a good industrial application prospect.
Disclosure of Invention
The invention aims to provide a novel method for preparing epiandrosterone by taking androstenedione as a raw material, which comprises the steps of taking androstenedione as a raw material, carrying out four reactions of alkene esterification protection of 3-carbonyl, ketal protection of 17-carbonyl, alkaline hydrolysis reduction and acidic hydrolysis, and finally successfully synthesizing epiandrosterone by a simpler process and higher yield. The method comprises the following specific steps:
(a) under the conditions of protective atmosphere and catalyst existence, dissolving androstenedione, adding acetic anhydride, reacting at 20-80 ℃ for 5-30h, and separating and purifying to obtain a product (2);
Figure GDA0001787860640000032
(b) uniformly mixing the product (2) with ethylene glycol, a water removing agent and p-toluenesulfonic acid, reacting for 2-10h at 20-40 ℃, quenching with triethylamine, and separating and purifying to obtain a product (3);
Figure GDA0001787860640000041
(c) dissolving the product (3), adding an alkaline reagent, stirring and reacting at 0-80 ℃ for 0.5-5h, adding a catalyst palladium-carbon, pressurizing at 20-100 ℃ for reduction reaction for 6-24h, and separating and purifying to obtain a product (4);
Figure GDA0001787860640000042
(d) dissolving the product (4), heating, adding an acidic reagent, stirring at 40-60 deg.C for hydrolysis, separating, and purifying to obtain epiandrosterone
Figure GDA0001787860640000043
According to the scheme, the mole ratio of androstenedione, acetic anhydride and the catalyst in the step (a) is 1: (5-20) (0.01-1), wherein the catalyst is selected from one of p-toluenesulfonic acid, sulfuric acid, hydrochloric acid and pyridine hydrochloride.
According to the above scheme, the molar ratio of the product (2) to ethylene glycol in step (b) is 1: (1-40), wherein the volume ratio of the ethylene glycol to the water removing agent is 1: (1-30), wherein the water removal agent is one of trimethyl orthoformate or triethyl orthoformate.
According to the scheme, the solvent used for dissolving the androstenedione, the product (3) and the product (4) in the steps (a), (c) and (d) is selected from one of methanol, ethanol, acetone, diethyl ether, dichloromethane and chloroform.
According to the scheme, the alkaline reagent in the step (c) is selected from one of potassium tert-butoxide, sodium hydroxide, potassium hydroxide and triethylamine, and the acidic reagent in the step (d) is selected from one of p-toluenesulfonic acid, hydrochloric acid, sulfuric acid, nitric acid and acetic acid.
According to the scheme, the mass ratio of the product (3) to the alkaline reagent in the step (c) is 10 (1-30), and the mass ratio of the catalyst palladium carbon to the product (3) is 1 (10-100).
According to the scheme, the catalyst palladium carbon is added in the step (c), and then the pressure is increased to 0.5-2MPa for reduction reaction.
According to the scheme, the pH value of the mixed solution is controlled between 1 and 4 by adding an acidic reagent in the step (d).
The palladium on carbon catalyst used in the present application is a black powder prepared by loading metal palladium powder on activated carbon. The palladium carbon is selected as an important catalyst in the synthesis process of the epiandrosterone, and the palladium carbon can catalyze and hydrogenate unsaturated hydrocarbon, and also has the advantages of high hydrogenation reducibility, good selectivity, stable performance, small feed ratio in use, repeated use, easy recovery and the like, so that the reduction step of an intermediate product can be simplified, and the product yield can be improved.
Compared with the prior art and method for synthesizing epiandrosterone, the method has the following beneficial effects:
(1) compared with the method of CN 105503985A, the method simplifies the production process by adopting cheap androstenedione as the raw material, not only ensures that the synthesis process is simpler and more controllable, but also greatly reduces the raw material cost, avoids using reagents such as lithium metal, ammonia water, tertiary butanol, isopropanol, potassium borohydride and the like with higher cost and larger dosage, greatly reduces the production cost and simultaneously reduces the pollution.
(2) The palladium-carbon catalyst has higher catalytic efficiency and is easier to filter and separate, the recovery method is simple and can be repeatedly used, and the use cost of the catalyst and the separation and purification cost of the product are further reduced.
(3) The yield and purity of the epiandrosterone product are higher, and the separation and purification are simpler.
Detailed Description
In order to make those skilled in the art fully understand the technical solutions and advantages of the present invention, the following embodiments are further described.
The method for synthesizing the epiandrosterone by utilizing the androstenedione comprises the following four steps:
firstly, adding androstenedione, acetic anhydride, a catalyst and an organic solvent into a three-neck flask under the protection of nitrogen, controlling the temperature to be 20-80 ℃, reacting for 5-30 hours, and then pouring the mixture into ice water for water precipitation to obtain an alkene esterification product 2;
secondly, adding the alkene esterification product 2 obtained in the first step into a three-neck flask, adding ethylene glycol, a water removing agent and p-toluenesulfonic acid, reacting for 2-10 hours at 20-40 ℃, adding triethylamine for quenching after the reaction is finished, removing the solvent, pouring into ice water, and performing water precipitation to obtain a product 3;
thirdly, dissolving the product 3 in an organic solvent, adding an alkaline reagent, stirring and reacting for 0.5-5h at 0-80 ℃, adding a catalyst palladium-carbon, pressurizing to 0.5-2MPa at 20-100 ℃, reacting for 6-24h, and removing the catalyst palladium-carbon (recycling) and the solvent after the reaction is finished to obtain a product 4;
and fourthly, dissolving the product 4 in an organic solvent, stirring for a certain time at room temperature, heating to 40-60 ℃, then adding an acidic reagent, carrying out magnetic stirring for hydrolysis reaction, and removing the solvent under reduced pressure after the reaction is finished to obtain the final product epiandrosterone. The complete detailed technical route is as follows:
Figure GDA0001787860640000061
example 1
Firstly, 100g (0.349mol) of androstenedione, 200mL (2.12mol) of acetic anhydride and 200mL of dichloromethane are sequentially added into a 1000mL three-neck flask protected by nitrogen, the temperature is controlled to be about 20 ℃, after stirring until the materials are completely dissolved, 4g (0.023mol) of p-toluenesulfonic acid is added, and condensation and reflux are carried out. The reaction was monitored by TLC, and after 20 hours the reaction was stopped, the reaction solution was poured into ice water for water separation, the solid was filtered off and dried in a vacuum oven to give 108g of crude product (2) in 108% weight yield.
In the second step, 40mL (0.366mol) of trimethyl orthoformate, 80mL (1.44mol) of ethylene glycol, 8g (0.046mol) of p-toluenesulfonic acid were reacted in a three-necked flask at 40 ℃ for 2 hours, and then 100g (0.305mol) of crude product (2) was added thereto, monitored by TLC (V)Petroleum ether：VEthyl acetate2: 1) and (4) reacting. After 6 hours, the reaction was essentially complete, triethylamine was added to quench the reaction, the pressure was reduced until a small portion of solvent remained, the remaining mixture was poured into 1L of ice water for water precipitation, and the solid was filtered off and dried under vacuum to give 102g of crude ketal product (3) in 102% weight yield.
And step three, taking 100g (0.269mol) of the crude ketal product (3), adding 40mL of methanol solution for dissolving, adding 10g of sodium hydroxide, stirring at 60 ℃ for 1h until the ketal product basically disappears, then adding 10g of palladium-carbon, and reacting in a high-pressure reaction kettle at 60 ℃ and 2MPa for 24 h. After the reaction is finished, the palladium-carbon is recovered by vacuum filtration, and 105g of crude product (4) after the ester decomposition and reduction is obtained after the methanol and the water are removed, the weight yield is 105%, and the purity of the product is 99% by HPLC.
And step four, taking 100g of the product (4) after the ester decomposition and reduction, adding 40mL of methanol solution, adding hydrochloric acid aqueous solution to adjust the pH value to be 1-4, reacting at room temperature, and monitoring the reaction by TLC. And (3) removing the solvent after the product (4) completely disappears to obtain a final product of epiandrosterone 102g, wherein the weight yield is 102%, and the purity of the product is 98% by HPLC (high performance liquid chromatography).
Example 2
The first step is the same as in example 1.
In the second step, 30mL (0.275mol) of trimethyl orthoformate, 100mL (1.80mol) of ethylene glycol and 20g of p-toluenesulfonic acid were reacted in a 1L three-necked flask at 20 ℃ for 2 hours, 80g (0.244mol) of the crude product obtained in the previous step was added, and the reaction was monitored by TLC. After 9 hours the reaction was essentially complete, triethylamine was added to quench the reaction, the solvent was removed under reduced pressure, the mixture was poured into ice water for water precipitation, the solid was filtered off and dried under vacuum to give 89g of crude ketal product (3) in 102.5% weight yield.
The subsequent steps were the same as in example 1.
Example 3
The first and second steps are the same as in example 1.
And step three, taking 100g (0.269mol) of the crude ketal prepared in the previous step, adding 40mL of methanol solution for dissolving, adding 10g of sodium tert-butoxide, stirring for 1h at 80 ℃ until the product (2) is completely disappeared, adding 10g of palladium-carbon, and reacting for 24h in a high-pressure reaction kettle at 80 ℃ and 2 MPa. After the reaction, the reaction solution was vacuum filtered, palladium on carbon was recovered, and methanol and water were removed to obtain 103g of the product (4) after the esterification and reduction, the weight yield was 103%, and the purity of the product by HPLC assay was 96%.
The fourth step is the same as in example 1.
Example 4
The first to third steps are the same as in example 1.
And step four, taking 100g of the product (4) after the ester decomposition and reduction, adding 40mL of methanol solution, adding 2g of p-toluenesulfonic acid, reacting at 80 ℃, and monitoring the reaction by TLC. And (3) obtaining 103g of final product epiandrosterone after the reaction is carried out until the product 4 completely disappears, wherein the weight yield is 103 percent, and the purity of the product is 97 percent by HPLC (high performance liquid chromatography).

Claims (4)

1.一种以雄烯二酮为原料制备表雄酮的方法，其特征在于包括以下步骤：1. a method for preparing epiandrostone with androstenedione as raw material, is characterized in that comprising the following steps: (a)在保护气氛及催化剂存在条件下，将雄烯二酮溶解，再加入醋酸酐于20-80℃反应5-30h，分离提纯得到产物(2)；(a) in the presence of a protective atmosphere and a catalyst, dissolving androstenedione, adding acetic anhydride and reacting at 20-80° C. for 5-30 hours, and separating and purifying to obtain the product (2);
Figure FDA0002316675770000011
Figure FDA0002316675770000011
 (b)产物(2)与乙二醇、除水剂、对甲苯磺酸混合均匀，在20-40℃下反应2-10h，用三乙胺淬灭后分离提纯得到产物(3)；(b) The product (2) is uniformly mixed with ethylene glycol, water scavenger and p-toluenesulfonic acid, reacted at 20-40° C. for 2-10 h, quenched with triethylamine, and then separated and purified to obtain the product (3);
Figure FDA0002316675770000012
Figure FDA0002316675770000012
 (c)将产物(3)溶解后加入碱性试剂，在0-80℃搅拌反应0.5-5h，再加入催化剂钯碳在20-100℃下加压反应6-24h，分离提纯得到产物(4)；(c) After dissolving the product (3), add an alkaline reagent, stir and react at 0-80°C for 0.5-5h, then add catalyst palladium-carbon and react under pressure at 20-100°C for 6-24h, and separate and purify to obtain the product (4). );
Figure FDA0002316675770000013
Figure FDA0002316675770000013
 (d)将产物(4)溶解并升温，再加入酸性试剂，在40-60℃下搅拌进行水解反应，分离提纯得到产物表雄酮(d) dissolving the product (4) and heating up, adding an acidic reagent, stirring at 40-60° C. to carry out a hydrolysis reaction, and separating and purifying to obtain the product epiandrosterone
Figure FDA0002316675770000014
Figure FDA0002316675770000014
 步骤(c)中所述碱性试剂选自叔丁醇钾、叔丁醇钠、氢氧化钠、氢氧化钾、三乙胺中的一种，产物(3)与碱性试剂的质量比为10:(1-30)，催化剂钯碳与产物(3)的质量比为1:(10-100)，加入催化剂钯碳后加压至0.5-2MPa进行还原反应；步骤(d)中加入酸性试剂控制混合溶液的pH在1-4之间，所述酸性试剂选自对甲苯磺酸、盐酸、硫酸、硝酸、醋酸中的一种；步骤(a)、步骤(c)、步骤(d)中溶解雄烯二酮、产物(3)、产物(4)所使用的溶剂选自甲醇、乙醇、丙酮、乙醚、二氯甲烷、氯仿中的一种。The alkaline reagent described in step (c) is selected from a kind of in potassium tert-butoxide, sodium tert-butoxide, sodium hydroxide, potassium hydroxide, triethylamine, and the mass ratio of product (3) and alkaline reagent is 10:(1-30), the mass ratio of catalyst palladium carbon and product (3) is 1:(10-100), after adding catalyst palladium carbon, pressurize to 0.5-2MPa to carry out reduction reaction; add acidity in step (d) The pH of the reagent control mixed solution is between 1-4, and the acidic reagent is selected from one of p-toluenesulfonic acid, hydrochloric acid, sulfuric acid, nitric acid, and acetic acid; step (a), step (c), step (d) The solvent used for dissolving androstenedione, product (3) and product (4) in the medium is selected from one of methanol, ethanol, acetone, diethyl ether, dichloromethane and chloroform. 2.如权利要求1所述的制备表雄酮的方法，其特征在于：步骤(a)中雄烯二酮、醋酸酐、催化剂的摩尔比为1:(5-20):(0.01-1)。2. the method for preparing epiandrosterone as claimed in claim 1, is characterized in that: in step (a), the mol ratio of androstenedione, acetic anhydride, catalyzer is 1:(5-20):(0.01-1 ). 3.如权利要求1所述的制备表雄酮的方法，其特征在于：步骤(b)中产物(2)与乙二醇的摩尔比为1：(1-40)，乙二醇与除水剂的体积比为1：(1-30)。3. the method for preparing epiandrosterone as claimed in claim 1, is characterized in that: in step (b), the mol ratio of product (2) and ethylene glycol is 1: (1-40), ethylene glycol and removing The volume ratio of the water agent is 1:(1-30). 4.如权利要求1所述的制备表雄酮的方法，其特征在于：所述催化剂选自对甲苯磺酸、硫酸、盐酸、吡啶盐酸盐中的一种，所述除水剂为原甲酸三甲酯或原甲酸三乙酯中的一种。4. the method for preparing epiandrosterone as claimed in claim 1 is characterized in that: described catalyzer is selected from a kind of in p-toluenesulfonic acid, sulfuric acid, hydrochloric acid, pyridine hydrochloride, and described dewatering agent is the original One of trimethyl formate or triethyl orthoformate.
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Title
《Allopregnanolone and Pregnanolone Analogues Modified in the C Ring: Synthesis and Activity》;Barbora Slavíkováet al.;《J. Med. Chem.》;20130219;第56卷(第6期);第2323-2336页 *

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