CN113912661B - Synthesis method of 7-hydroxy steroid compound - Google Patents
Synthesis method of 7-hydroxy steroid compound Download PDFInfo
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- C07J9/005—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of more than two carbon atoms, e.g. cholane, cholestane, coprostane containing a carboxylic function directly attached or attached by a chain containing only carbon atoms to the cyclopenta[a]hydrophenanthrene skeleton
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Abstract
The invention provides a synthetic method of a 7-hydroxy steroid compound, which comprises the following steps: the compound I is used as an initial raw material, and is subjected to 6, 7-site dehydrogenation, oxidation or epoxidation reaction, ring opening reaction and 6-site halogen removal in sequence to respectively obtain the 7 alpha-hydroxy steroid compound or the 7 beta-hydroxy steroid compound. The raw materials and the auxiliary materials of the synthesis method of the 7-hydroxy steroid compound are simple and easy to obtain, the substrate universality is wide, the selectivity of synthesizing the 7 alpha-hydroxy steroid compound or the 7 beta-hydroxy steroid compound is high, and the purity and the yield of the obtained product are high.
Description
Technical Field
The invention relates to the technical field of pharmaceutical chemistry synthesis, in particular to a synthesis method of a 7-hydroxy steroid compound.
Background
7-hydroxysteroids are a very important class of compounds, which are starting materials for the synthesis of many important drug molecules and intermediates. Many steroid natural products or drug molecules have chiral 7-hydroxyl groups, such as cholic acid, chenodeoxycholic acid and obeticholic acid in cholic acid series products all contain 7 alpha-hydroxyl groups, and natural antibacterial steroid shark polyamine also contains 7 alpha-hydroxyl groups, and drug molecules such as ursodeoxycholic acid and the like have 7 beta-hydroxyl groups. The 7-hydroxy steroid is generally extracted from animal viscera, has limited sources and high cost, and does not meet the requirements of environmental protection.
In the process of chemically synthesizing the 7-hydroxy steroid compound, the introduction and construction of the 7-hydroxy group is always a key and difficult point, especially the problem of the selectivity control of 7 alpha-hydroxy group and 7 beta-hydroxy group, because the 7-position and adjacent sites in the general steroid compound have no active groups.
Disclosure of Invention
Based on the technical problems in the prior art, the invention provides a method for synthesizing 7-hydroxy steroid compounds, by which 7 alpha-hydroxy steroid compounds or 7 beta-hydroxy steroid compounds can be selectively synthesized, and the yield and purity are high.
In order to achieve the above object, the technical scheme of the present invention is as follows:
a synthetic method of 7-hydroxy steroid compound comprises the following steps:
s1, taking a compound I as a starting material, and carrying out 6, 7-position dehydrogenation to obtain a compound II; the structure of the compound I is as follows:the structure of the compound II is as follows: />
S2, carrying out oxidation reaction on the compound II under the action of oxide to obtain a compound IIIa; or, the compound II undergoes a hydroxyhalogenation reaction under the action of a halogenating reagent to generate a compound IIa or a compound IIb, and then the compound IIa or the compound IIb undergoes an epoxy condensation reaction under an alkaline condition to obtain a compound IIIb; the structure of the compound IIIa is as follows:the structure of the compound IIa is as follows: />The structure of the compound IIb is as follows: />The structure of the compound IIIb is as follows: />
S3, carrying out ring-opening reaction on the compound IIIa or the compound IIIb under the condition of halogen-containing Lewis acid to obtain a compound IVa or a compound IVb respectively; the structure of the compound IVa is as follows:the structure of IVb is: />
S4, removing 6-position halogen X from the compound IVa or the compound IVb under the action of a reducing agent to obtain a 7 alpha-hydroxyl compound Va or a 7 beta-hydroxyl compound Vb respectively; the structure of the compound Va is as follows:the said
Wherein R is 1 is-H, -OH or-CH 3 ;R 2 is-H, -CH 3 or-OH; r is R 3 is-H, carbonyl or-OH; r is R 4 is-H, carbonyl or-OH; r is R 5 is-H, carbonyl, -OH, C 1 -C 10 Alkyl group of (C), X is one of-Cl, -Br and-I.
In some embodiments, in step S3, the halogen-containing lewis acid is selected from at least one of hydrochloric acid, hydrobromic acid, lithium chloride, lithium bromide, sodium bromide, potassium bromide, sodium chloride, potassium iodide, and sodium iodide.
In some embodiments, in step S4, the reducing agent is selected from at least one of zinc powder, magnesium powder, palladium on carbon, ruthenium on carbon, and raney nickel.
In some embodiments, in step S2, the peroxide is selected from at least one of hydrogen peroxide, peracetic acid, m-chloroperoxybenzoic acid, t-butyl hydroperoxide, monoperoxyphthalic acid, and monoperoxyphthalic acid magnesium. Preferably, the peroxide is monoperoxyphthalic acid.
In some embodiments, in step S2, the reaction temperature of the oxidation reaction is-10 ℃ to 40 ℃.
In some embodiments, in step S2, the halogenated reagent is selected from at least one of bromosuccinimide, chlorosuccinimide, iodosuccinimide, dibromohydantoin, dichlorohydantoin, hypochlorous acid, sodium hypochlorite, hypobromous acid, and sodium hypobromite.
In some embodiments, in step S2, the temperature of the hydroxyhalogenation reaction is from-10 ℃ to 40 ℃; and/or the temperature of the epoxy condensation reaction is 0-10 ℃.
In some embodiments, in the step S2, the base used in the epoxy condensation reaction is at least one selected from triethylamine, pyridine, sodium carbonate, sodium hydroxide, potassium carbonate and cesium carbonate.
In some embodiments, in step S1, the compound i is directly dehydrogenated under the catalysis of tetrachlorobenzoquinone and an acid to obtain the compound ii; or the compound I is firstly prepared into a 6-position halogenated product, and then the 6-position halogen is eliminated to obtain the compound II.
Compared with the prior art, the invention has the following beneficial effects:
the invention takes steroid compounds with a certain structure as raw materials, and obtains the high-purity 7-hydroxy steroid compounds through 6, 7-dehydrogenation, 6, 7-epoxy condensation, ring-opening reaction and 6-dehalogenation. According to the scheme, the problem that 7-position hydroxyl substitution cannot be obtained in a controlled manner in the ring-opening reaction process in the prior art is solved, the ring-opening reaction is carried out by using the halogen-containing Lewis acid, positive ions are stable at the allyl position during ring opening of the Lewis acid, and the ring-opened SN1 reaction is dominant, so that the 7-position hydroxyl substituted steroid compound is controllably obtained, and the obtained finished product is high in purity.
In addition, the invention can also selectively obtain 7 alpha-hydroxysteroid or 7 beta-hydroxysteroid, which is specifically as follows: the compound III is directly epoxy to obtain a compound IIIa, and then 7 alpha-hydroxy steroid compound is obtained through ring opening and reduction reaction; the compound III firstly undergoes a hydroxylation halogenation reaction and then undergoes epoxy condensation to obtain a compound IIIb, and finally undergoes a ring opening and reduction reaction to obtain the 7 beta-hydroxysteroid compound.
The synthesis method has the advantages of simple and easily obtained raw materials and auxiliary materials, wide substrate universality and simple process, and is suitable for industrial application.
In addition, in the process of preparing the 6, 7-epoxy steroid compound by peroxide oxidation of the compound II, specific magnesium monoperoxyphthalate is selected as peroxide, so that the conversion rate of the compound IIa can be greatly improved, and the yield of the 7-hydroxy steroid compound is further improved.
Detailed Description
In the following description, numerous specific details are set forth in order to provide a thorough understanding of the present invention. The invention may be embodied in many other forms than described herein and similarly modified by those skilled in the art without departing from the spirit or scope of the invention, which is therefore not limited to the specific embodiments disclosed below.
The invention aims to provide a synthesis method of a 7-hydroxy steroid compound, which takes common 4-alkene-3-ketone steroid molecules (compound I) as raw materials, and sequentially carries out 6-7 dehydrogenation, 6,7 epoxy locking, ring opening reaction and 6 dehalogenation reaction controllability to obtain the 7-hydroxy steroid compound, and comprises the following steps:
s1, taking a compound I as a starting material, and carrying out 6, 7-position dehydrogenation to obtain a compound II; the structure of the compound I is as follows:the structure of the compound II is as follows: />
S2, carrying out oxidation reaction on the compound II under the action of oxide to obtain a compound IIIa; or, the compound II undergoes a hydroxyhalogenation reaction under the action of a halogenating reagent to generate a compound IIa or a compound IIb, and then the compound IIa or the compound IIb undergoes an epoxy condensation reaction under an alkaline condition to obtain a compound IIIb; the structure of the compound IIIa is as follows:the structure of the compound IIa is as follows: />The structure of the compound IIb is as follows: />The structure of the compound IIIb is as follows: />
S3, carrying out ring-opening reaction on the compound IIIa or the compound IIIb under the condition of halogen-containing Lewis acid to obtain a compound IVa or a compound IVb respectively; the structure of the compound IVa is as follows:the structure of IVb is: />
S4, removing 6-position halogen X from the compound IVa or the compound IVb under the action of a reducing agent to obtain a 7 alpha-hydroxyl compound Va or a 7 beta-hydroxyl compound Vb respectively; the structure of the compound Va is as follows:said->
The technical scheme has the advantages of simple and easily obtained raw materials and auxiliary materials, wide sources, wide substrate universality, simple and effective process, good selectivity, high purity and high yield, and can effectively obtain the 7-hydroxy steroid compound with a specific structure.
In the above scheme, preferably, in step S1, the compound i is directly dehydrogenated under the catalysis of tetrachlorobenzoquinone and acid to obtain the compound ii; or the compound I is firstly prepared into 6-position halogenated product, then 6-position halogen is eliminated to obtain compound II,
in step S2, the peroxide is at least one selected from hydrogen peroxide, peracetic acid, m-chloroperoxybenzoic acid (m-CBPA), tert-butyl hydroperoxide, monoperoxyphthalic acid and monoperoxyphthalic acid magnesium (MMPP). Preferably, the peroxide is selected from magnesium monoperoxyphosphate diformate and/or monoperoxyphthalic acid.
Further, the peroxide is used in an amount of 1 to 3 molar equivalents, preferably 1.2 molar equivalents. The reaction temperature of the oxidation reaction is-10 to 40 ℃, preferably 5 ℃.
Specifically, step S2 is oxidized by peroxide, and the synthetic method of the 7-hydroxy steroid compound is as follows, and the obtained product is 7 alpha-hydroxy compound Va.
In another embodiment, in step S2, the halogenated agent is selected from at least one of NBS (bromosuccinimide), NCS (chlorosuccinimide), NIS (iodosuccinimide), dibromohydantoin, dichlorohydantoin, hypochlorous acid, sodium hypochlorite, hypobromous acid, and sodium hypobromite. NCS is preferably used in an amount of 1 to 4 molar equivalents, preferably 1.6 molar equivalents.
Further, the temperature of the hydroxylation reaction is-10℃to 40℃and preferably the reaction temperature is 5 ℃.
Further, in step S2, the base used in the epoxy condensation reaction is at least one selected from triethylamine, pyridine, sodium carbonate, sodium hydroxide, potassium carbonate and cesium carbonate; potassium hydroxide is preferred. Further, the temperature of the epoxy condensation reaction is 0 to 10 ℃.
In one embodiment, in step S3, the halogen-containing lewis acid is selected from at least one of hydrochloric acid, hydrobromic acid, lithium chloride, lithium bromide, sodium bromide, potassium bromide, sodium chloride, potassium iodide, and sodium iodide.
In step S3, the halogen-containing Lewis acid is preferably hydrochloric acid having a concentration of 37% by weight; the reaction solvent in step S3 is at least one selected from the group consisting of hydrochloric acid, acetone, methanol, glacial acetic acid, tetrahydrofuran, N-Dimethylformamide (DMF) and dioxane, preferably acetone.
Further, the reaction temperature in step S3 is 0 to 25 ℃.
In a specific example, 0.5 volume of acetone is added into 2 volumes of concentrated hydrochloric acid, and the compound IIIa is slowly added at room temperature to perform ring opening reaction to generate a compound IVa.
In one embodiment, in step S4, the reducing agent is at least one selected from zinc powder, magnesium powder, palladium carbon, ruthenium carbon and raney nickel; zinc powder is preferred.
In the step S4, the zinc powder is reduced under the condition of glacial acetic acid, and the reaction temperature is 0-80 ℃, preferably 25 ℃. In a specific example, glacial acetic acid is used as a solvent, and the compound IVa or the compound IVb is added, zinc powder is slowly added in batches at 25 ℃, the amount of the zinc powder is 2-5 molar equivalents of the substrate, water separation is carried out, and the 7α -hydroxy compound Va or 7β -hydroxy compound vb is obtained through separation.
Further, the compound I is selected from one of the following compounds:
in order that the above objects, features and advantages of the invention will be readily apparent, a more particular description of the invention will be rendered by reference to specific embodiments thereof. In the following description, numerous specific details are set forth in order to provide a thorough understanding of the present invention. The invention can be implemented in many different and yet again described other ways. Similar modifications can be made by those skilled in the art without departing from the spirit of the invention, and therefore the invention is not limited to the specific embodiments disclosed below, i.e., the following examples merely facilitate a better understanding of the invention, but do not limit the invention.
Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. The terminology used herein in the description of the invention is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention.
Example 1
A synthetic method of 7-hydroxy steroid compound (compound Va 1) is shown in the following synthetic route:
the method specifically comprises the following steps:
(1) Synthesis of Compound II 1: into a three-neck flask with a thermometer and a stirring magnet, 20g of a compound I1, 100mL of toluene, 1g of p-toluenesulfonic acid and 16g of tetrachlorobenzoquinone are added, the mixture is stirred uniformly, the mixture is heated to 95-100 ℃ for reaction for 4-6 hours under the protection of nitrogen, and the TLC detects that the reaction raw materials completely disappear (volume ratio of benzene to acetone=6:1) and the reaction is stopped. Cooling to room temperature, adding 50mL of ethyl acetate and 100mL of saturated sodium bicarbonate solution for washing twice, concentrating under reduced pressure to dryness, adding 20mL of methanol at 40-45 ℃ for pulping for 1h, cooling to 0-10 ℃ for stirring for 30min, filtering, leaching a filter cake with a proper amount of glacial methanol, and drying at 50-60 ℃ to obtain a light brown compound II 1, 17.1g, wherein the yield is 86%, and the purity is 95.5%;
(2) Synthesizing a compound IIIa 1, adding 20g of a compound II 1 and 100mL of ethyl acetate into a three-neck flask with a thermometer and a stirring magnet, cooling to 0-10 ℃ in an ice bath, slowly dropwise adding 60mL of an ethyl acetate solution (1 mol/L) of the existing monoperoxyphthalic acid, keeping the temperature for 16h after 3h dropwise adding, and completely adding 10mL of peroxide if the reaction is not completed; 20mL of sodium sulfite aqueous solution (20%), 80mL of sodium carbonate (20%) aqueous solution are added, stirring is carried out for 10min, liquid separation is carried out, the organic layer is washed once by saturated saline water, ethyl acetate is concentrated to a small volume, the temperature is reduced to 0-5 ℃ for crystallization for 2h, filtration is carried out, and the light brown compound IIIa 1, 13.7g is obtained after drying at 50-60 ℃. Yield 66%, purity 94.6%;
(3) Synthesis of Compound IVa 1: 90mL of concentrated hydrochloric acid (37%) and 30mL of acetone are added into a three-neck flask with a thermometer and a stirring magnet, and the mixture is stirred uniformly; at room temperature, 30g of compound IIIa 1 is slowly added into hydrochloric acid solution for 10 times, the addition is completed for 2 hours, the heat preservation reaction is continued for 2 hours, the TLC detection is completed, 1000mL of ice water is added into the system, the solid is separated out, the filtration is carried out, the filter cake water is washed to be neutral, the white solid IVa 1 is obtained by drying at 35-45 ℃, the yield is 97%, and the purity is 96%;
(4) Synthesis of compound va 1: 20g of compound IVa 1, 60mL of acetone and 20mL of glacial acetic acid are added into a three-neck flask with a thermometer and a stirring magnet, and 12g of zinc powder is slowly added in batches at 25 ℃; after the reaction, filtering, and separating out the filtrate to obtain 7 alpha-hydroxy compound Va1, 17g, 92% yield and 96% purity.
Example 2
A method for synthesizing 7-hydroxy steroid compound (compound Va 2), the synthetic route is as follows:
the method specifically comprises the following steps:
(1) The synthesis step of the compound II 2 is basically the same as that of the compound II 1;
(2) Synthesis of Compound IIIb 2: adding 20g of a compound II 2, 100mL of acetone and 20mL of water into a three-neck flask with a thermometer and a stirring magnet, cooling to 0-5 ℃ in an ice bath, adding 8g of NCS for 4 times, and carrying out heat preservation reaction for 1-2h after the addition to obtain a mixture of an intermediate IIa 2 and an intermediate IIb 2; slowly adding 16mL of 30% potassium hydroxide aqueous solution, carrying out an epoxy reaction at 0-10 ℃, adding glacial acetic acid to adjust the PH to be neutral after the reaction is finished, concentrating part of solvent, carrying out water precipitation to obtain a crude product, adding 30mL of methanol into the crude product, pulping for 1h, cooling to 0-5 ℃ for crystallization for 1h, filtering, and drying to obtain 15g of a compound IIIb 2 with the yield of 72% and the purity of 93%;
(3) Synthesis of Compound IVb 2: adding 20mL of hydrobromic acid (40%) into a three-neck flask with a thermometer and a stirring magnet, adding 20mL of acetone, stirring uniformly, slowly adding 30g of compound IIIb 2 into hydrobromic acid solution for 5 times at room temperature, after 1 hour, continuing to perform heat preservation reaction for 2 hours, adding 500mL of ice water into the system after TLC detection is completed, separating out solids, filtering, flushing filter cake water to be neutral, and obtaining a wet product of the compound IVb 2; the wet product was used directly in the next reaction.
(4) Synthesis of compound vb 2: a three-necked flask equipped with a thermometer and stirring magnet was charged with 12g of zinc powder from the wet product of the above-mentioned compound IVb 2, 60mL of acetone, 20mL of glacial acetic acid and 25 ℃. After the reaction, filtering, separating out filtrate, filtering, adding 20mL of acetone into wet products, stirring and pulping for 1h at room temperature, cooling to 0-5 ℃, stirring and crystallizing for 1h, filtering and separating, and drying to obtain 7 beta-hydroxy compound vb 2, 16.4g. The total yield of the two steps from the step (3) to the step (4) is 82 percent (relative to IIIb 2), and the purity is 95 percent.
Example 3
A synthetic method of 7-hydroxy steroid compound is as follows:
the method specifically comprises the following steps:
(1) Synthesis of Compound II 3: the synthesis of II 1 in example 1 was essentially the same.
(2) Synthesizing a compound IIIa 3, adding 20g of a compound II 3 and 100mL of ethyl acetate into a three-neck flask with a thermometer and a stirring magnet, cooling to 0-10 ℃ in an ice bath, slowly dropwise adding 60mL of ethyl acetate solution (1 mol/L) of monoperoxyphthalic acid which is prepared at present, and continuing to perform heat preservation reaction for 16h after 3h dropwise adding is completed; then adding 20mL of sodium sulfite aqueous solution (20%), 80mL of sodium carbonate (20%) aqueous solution, stirring for 10min, separating, washing the organic layer with saturated saline water once, concentrating ethyl acetate to a small volume, cooling to 0-5 ℃ for crystallization for 2h, filtering, and drying at 50-60 ℃ to obtain a light brown compound IIIa 3, 15.6g, yield 75% and purity 95%;
(3) Synthesis of Compound IVa 3: 90mL of concentrated hydrochloric acid (37%) and 30mL of acetone are added into a three-neck flask with a thermometer and a stirring magnet, and the mixture is stirred uniformly; at room temperature, 30g of compound IIIa 3 is slowly added into hydrochloric acid solution for 10 times, the addition is completed for 2 hours, the heat preservation reaction is continued for 2 hours, the TLC detection is completed, 1000mL of ice water is added into the system, the solid is separated out, the filtration is carried out, the water of the filter cake is washed to be neutral, the white-like solid compound IVa 3, 32g is obtained after drying at 35-45 ℃, the yield is 97.8%, and the purity is 96%;
(4) Synthesis of compound va 3: adding 20g of compound IVa 3, 60mL of acetone and 20mL of glacial acetic acid into a three-neck flask with a thermometer and a stirring magnet, slowly adding 12g of zinc powder in batches at 25 ℃, and heating to 40 ℃ after the addition is finished to continue the reaction for 1h; after the reaction, the mixture was filtered, and the filtrate was centrifuged to obtain 7α -hydroxy compound va 3, 18g. The yield was 98% and the purity was 96%.
Example 4
Example 4 is essentially the same as example 1, except that R in the general formula of the starting compound I in example 3 1 Is OH.
The technical features of the above-described embodiments may be arbitrarily combined, and all possible combinations of the technical features in the above-described embodiments are not described for brevity of description, however, as long as there is no contradiction between the combinations of the technical features, they should be considered as the scope of the description.
The above examples illustrate only a few embodiments of the invention, which are described in detail and are not to be construed as limiting the scope of the invention. It should be noted that it will be apparent to those skilled in the art that several variations and modifications can be made without departing from the spirit of the invention, which are all within the scope of the invention. Accordingly, the scope of protection of the present invention is to be determined by the appended claims.
Claims (5)
1. The synthesis method of the 7-hydroxy steroid compound is characterized by comprising the following steps:
s1, taking a compound I as a starting material, and carrying out 6, 7-position dehydrogenation to obtain a compound II; the structure of the compound I is as follows:the structure of the compound II is as follows: />
S2, carrying out oxidation reaction on the compound II under the action of peroxide to obtain a compound IIIa; or, the compound II undergoes a hydroxyhalogenation reaction under the action of a halogenating reagent to generate a compound IIa or a compound IIb, and then the compound IIa or the compound IIb undergoes an epoxy condensation reaction under an alkaline condition to obtain a compound IIIb; the structure of the compound IIIa is as follows:the structure of the compound IIa is as follows: />The structure of the compound IIb is as follows: />The structure of the compound IIIb is as follows:
the preparation method of the compound IIIa comprises the following steps:
adding 20g of compound II and 100mL of ethyl acetate into a three-neck flask with a thermometer and a stirring magnet, cooling to 0-10 ℃ in ice bath, dropwise adding 60mL of ethyl acetate solution of 1mol/L monoperoxyphthalic acid, keeping the temperature for 16h after 3h dropwise adding, and finishing the reaction; adding 20mL of 20% sodium sulfite aqueous solution and 80mL of 20% sodium carbonate aqueous solution, stirring for 10min, separating, washing the organic layer with saturated saline solution once, concentrating ethyl acetate, cooling to 0-5 ℃ for crystallization for 2h, filtering, and drying at 50-60 ℃ to obtain a compound IIIa;
the preparation method of the compound IIIb comprises the following steps:
adding 20g of compound II, 100mL of acetone and 20mL of water into a three-neck flask with a thermometer and a stirring magnet, cooling to 0-5 ℃ in an ice bath, adding 8g of NCS for 4 times, and carrying out heat preservation reaction for 1-2h after the addition; then adding 16mL of 30% potassium hydroxide aqueous solution, carrying out an epoxy reaction at 0-10 ℃, adding glacial acetic acid to adjust the PH to be neutral after the reaction is finished, concentrating part of solvent, carrying out water precipitation to obtain a crude product, adding 30mL of methanol into the crude product, pulping for 1h, cooling to 0-5 ℃ for crystallization for 1h, filtering, and drying to obtain a compound IIIb;
s3, carrying out ring-opening reaction on the compound IIIa or the compound IIIb under the condition of halogen-containing Lewis acid to obtain a compound IVa or a compound IVb respectively; the structure of the compound IVa is as follows:the structure of IVb is: />
S4, removing 6-position halogen X from the compound IVa or the compound IVb under the action of a reducing agent to obtain a 7 alpha-hydroxyl compound Va or a 7 beta-hydroxyl compound Vb respectively; the structure of the compound Va is as follows:the said
Wherein R is 1 is-H, -OH or-CH 3 ;R 2 is-H, -CH 3 or-OH; r is R 3 is-H, carbonyl or-OH; r is R 4 is-H, carbonyl or-OH; r is R 5 is-H, carbonyl, -OH, C 1 -C 10 Alkyl group of (C),
2. The method for synthesizing a 7-hydroxysteroid compound according to claim 1, wherein in step S3, the halogen-containing lewis acid is at least one selected from the group consisting of hydrochloric acid, hydrobromic acid, lithium chloride, lithium bromide, sodium bromide, potassium bromide, sodium chloride, potassium iodide and sodium iodide.
3. The method for synthesizing 7-hydroxysteroid according to claim 1, wherein in step S4, the reducing agent is at least one selected from the group consisting of zinc powder, magnesium powder, palladium on carbon, ruthenium on carbon, and raney nickel.
4. The method for synthesizing 7-hydroxysteroid compound according to claim 1, wherein in step S1, the compound i is directly dehydrogenated under the catalysis of tetrachlorobenzoquinone and acid to obtain the compound ii; or the compound I is firstly prepared into a 6-position halogenated product, and then the 6-position halogen is eliminated to obtain the compound II.
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