- Synthesis of 17α-Hydroxy-20-oxo-pregnanes from 17(20)-Dehydro-23,24-dinorcholan-22-oic Acids
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Title transformation involving catalytic epoxidation, Curtius rearrangement and acidic hydrolysis has been accomplished.This synthetic sequence offers a novel route from a partial microbial side chain degradation product of natural sterols into useful precursors of antiinflammatory, antiandrogen and gestagen pharmaceuticals.
- Toro, Andras,Ambrus, Gabor
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- Method for preparing 17alpha-hydroxy androstane-4,9-diene-3,20-dione
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The invention discloses a method for preparing 17alpha-hydroxyl androstane-4,9-diene-3,20-diketone, and the method comprises the following steps: (1) dispersing a ketal protector (I) in an organic solvent, and carrying out Grignard reaction in a tubular reactor filled with a catalyst; (2) carrying out a deprotection reaction on the obtained Grignard reaction raw material solution in a tubular reactor filled with strongly acidic ion exchange resin to prepare an intermediate ketone (II); (3) carrying out post-treatment on the feed liquid subjected to the deprotection reaction to obtain 17alpha-hydroxyl androstane-4,9-diene-3,20-diketone (III). According to the invention, the continuous tubular reaction technology is used for replacing the existing interval kettle type reaction to prepare 17alpha-hydroxyl androstane-4,9-diene-3,20-diketone, so the automatic control of the process is easy to realize, the continuous production is convenient, and the process stability is improved.
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Paragraph 0011; 0026-0043
(2021/04/07)
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- An efficient procedure for the synthesis of 21-acetoxypregna-1,4,9(11),16-tetraene-3,20-dione
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Background: Halogenated corticosteroids are widely used in medicine, and the global need of these steroidal APIs is estimated to be 40 - 70 tons, annually. Vietnam currently imports the pharmaceutical compounds up to 90%, in particular 100% of steroidal drugs. Currently, industrial production is based on the chemical syntheses of corticosteroids from either 16-dehydropregnenolone acetate (obtained from diosgenin) or androstenedione (obtained from phytosterol). The development of shorter synthetic schemes and more economically feasible technologies is of great significance. Introduction of 1(2)-double bond at the final stages of the corticosteroids synthesis results inpoor yield. 21-Acetoxypregna-1,4,9(11),16-tetraene-3,20-dione (tetraene acetate) is a key intermediate in the synthesis of highly active halogenated corticosteroids such as dexamethasone and other halogenated corticosteroids. 21-acetoxypregna-1,4,9(11),16-tetraene-3,20-dione is a key intermediate in the synthesis of dexamethasone from the readily available and cheap 9α-hydroxyandrost-4-ene-3,17-dione. Objective: The purpose of this study was the development of an efficient and shorter procedure for the synthesis of 21-acetoxypregna-1,4,9(11),16-tetraene-3,20-dione from 9α-hydroxyan-drostenedione, which is a product of a bio-oxidative degradation of the side chain of phytosterols. Methods: Pregnane side chain was constructed using cyanohydrin method. For 1(2)-dehydrogenation, selene dioxide was applied for the introduction of Δ1(2)-double bond. Other stages of the synthesis were epimerization, Stork’s iodination procedure and dehydration. Result: 21-Acetoxypregna-1,4,9(11),16-tetraene-3,20-dione was prepared from 9α-hydroxyandrostenedione in yield more than 46%. Conclusion: An efficient and practically feasible procedure for the synthesis of 21-acetoxypregna-1,4,9(11),16-tetraene-3,20-dione from 9α-hydroxyandrostenedione, a key intermediate for the synthesis of 9-haloidated corticoids, has been developed. The procedure can be applied for the production of value-added 9-haloidated corticoids.
- Huy, Luu D.,Diep, Nguyen T.,Vu, Tran K.,Savinova, Tatiana S.,Donova, Marina V.
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p. 225 - 231
(2020/04/27)
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- Methylprednisolone intermediate debrominated product and preparation method thereof
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The invention discloses a methylprednisolone intermediate debrominated product and a preparation method thereof. According to the preparation method, a compound shown as a formula I is used as a raw material, and a dechlorination reaction, a bromination reaction, a debromination reaction and an oxidation reaction are sequentially performed to prepare a compound (debrominated substance) shown as aformula V. The preparation method has the advantages of short synthetic route, high yield, low cost and easily available raw materials, is suitable for industrial production, and has very high industrial value.
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Paragraph 0034; 0036; 0040; 0041
(2020/02/10)
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- Fluorometholone, fluorometholone acetate, and preparation method thereof
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The invention discloses fluorometholone, fluorometholone acetate, and a preparation method thereof. According to the preparation method, a compound represented by a formula (II) is taken as a raw material, the compound carries out de-chlorination reaction, esterification reaction, methenylation reaction, hydrogenation reaction, fermentation de-hydrogenation reaction, epoxidation reaction, and ring-opening reaction in sequence to obtain derivatives of fluorometholone; and fluorometholone derivatives carry out hydrolysis to obtain fluorometholone. The preparation method has the advantages of short synthesis route, high yield, low raw material cost, easily available raw materials, simple and convenient purification, high product purity, and strong technological operability, is suitable for industrial production, and has a high industrialization value.
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Paragraph 0040-0042; 0051-0053; 0060-0062
(2020/03/12)
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- Synthetic method of Delta-9,11-hydroxyl progesterone
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The invention discloses a synthetic method of Delta-9,11-hydroxyl progesterone. The synthetic method comprises the following steps: (1) a siloxane reaction: carrying out the siloxane on a 17-beta-cyano substance, chloromethyl chlorosilane and a catalyst in a solvent to obtain a siloxane substance; (2) a chloromethylation reaction: carrying out the reaction on the siloxane, LDA and concentrated hydrochloric acid and adjusting the pH of the system after the reaction to obtain a chloromethyl substance; and (3) a reduction reaction: carrying out the reaction on the chloromethyl substance, a reducer and concentrated hydrochloric acid, and concentrating and separating out crystals to obtain the Delta-9,11-hydroxyl progesterone. The initial raw material 17-beta-cyano is originated from a biofermented product 9-OH AD, the production links are green and environment-friendly, and no heavy metal chromium is generated. The cost of the synthetic method is reduced greatly compared with that of conventional processes. In addition, the product quality is improved greatly compared with that of conventional processes. The product yield can reach 90-95%, and the HPLC purity reaches over 99.5%.
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Paragraph 0021; 0024; 0026; 0029
(2019/04/14)
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- Metal-Free Iodine-Mediated Deoxygenation of Alcohols in the Position α to Electron-Withdrawing Groups
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The use of a substoichiometric amount of molecular iodine in the presence of PPh3 and pyridine effects a direct deoxygenation of primary and secondary alcohols in positions α to a variety of activating electron-withdrawing groups, including ketones, esters, amides, imides and nitrile groups.
- Pichon, Ma?va M.,Stauffert, Fabien,Addante-Moya, Luis G.,Bodlenner, Anne,Compain, Philippe
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p. 1538 - 1545
(2018/04/20)
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- Preparation method of 17alpha-acetoxy-(8, 13)-ene-11alpha-hydroxyprogesterone
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The invention relates to the field of compound preparation, in particular to a preparation method of 17alpha-acetoxy-(8, 13)-ene-11alpha-hydroxyprogesterone. The method includes: taking 11alpha, 17alpha-dihydroxyprogesterone as the raw material, carrying out elimination reaction, esterification reaction, bromination epoxy reaction and fluorination reaction to synthesize a 17alpha-acetoxy-(8, 13)-ene-11alpha-hydroxyprogesterone crude product; and finally performing column chromatography to obtain the high purity target object 17alpha-acetoxy-(8, 13)-ene-11alpha-hydroxyprogesterone refined product. The invention mainly solves the problem that the existing technology is short of synthesis method of the product, the product can be used as a reference substance for quality control of flurogestone acetate, is more beneficial to control of the flurogestone acetate quality and improvement of the drug safety.
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Paragraph 0010; 0084-0087; 0100; 0113; 0126
(2018/04/01)
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- Preparation method of steroidal compound with multiple olefin groups
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The invention relates to a preparation method of a steroid medicine intermediate body, in particular to a method for preparing a steroid carrying medicine intermediate body, namely steroid carrying-1,4,9(11),16(17)-tetraterpene-3,20-diketone and steroid carrying-4,9(11)-diene-3,20-diketone-17 alpha-hydroxyl, by taking androstane-4-alkene-3,17-diketone as a substrate.
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Paragraph 0110-0111; 0114-0115
(2017/11/04)
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- Preparation method of dexamethasone intermediate
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The invention discloses a preparation method of a dexamethasone intermediate. According to the preparation method of the dexamethasone intermediate, a compound 17beta-cyano-17alpha-hydroxyandrost-4,9-diene-3-one is taken as a starting material and has a 3-site keto-carbonyl protective reaction, a 17-site hydroxyl protective reaction, a Grignard reaction, a 3-site keto-carbonyl deprotection reaction, a dehydration reaction and a dehydrogenation reaction, and 5ST tetraene methyl is obtained. The starting material 17beta-cyano-17alpha-hydroxyandrost-4,9-diene-3-one has abundant sources and is low in cost, further, the process route design is novel, the production process has small influence on the environment, the overall yield is high, and the preparation method of the dexamethasone intermediate has higher competitiveness and is suitable for industrial production.
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Paragraph 0055; 0056; 0057; 0058; 0059
(2016/10/31)
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- 9-alpha-hydroxy steroids, process for their preparation, process for the preparation of the corresponding 9(11)-dehydro derivatives and pharmaceutical preparations containing such steroids
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New 9-alphahydroxy steroids are prepared by the introduction of substituents on the D-ring of 9-alpha-hydroxy-androst-4-ene-3,17-dione. The resulting compounds are useful intermediates in the synthesis of corticosteroids.
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- 17β-cyano-9α,17α-dihydroxyandrost-4-en-3-one
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The invention is the compound 17β-cyano-9α, 17α-dihydroxyandrost-4-en-3-one (I) which is particularly useful as an intermediate in the production of the 17α-halo silyl ethers (II).
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- Epi-ethynylation process
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Ethynylation of 17-keto steroids (I) by standard means in the presence of a polar amine solvent produces the epi (17β-ethynyl-17α-hydroxy) configuration at C17. The epi-ethisterone compounds are useful intermediates in the production of 17α-hydroxyprogesterones.
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- Process for preparing 9,11-unsaturated steroidal compound from the corresponding saturated steroidal compound
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The present invention provides a non-fermentation process for placing unsaturation at the 9,11 position in a steroidal compound. Also, the present invention provides a process whereby the modified steroidal compound can be separated from the reaction mixture without the use of chromatography. More specifically, the present invention provides a process whereby a steroid compound such as 17-α-hydroxy-progesterone is reacted to form the meta iodoaryl benzoate. The iodoarylbenzoate is then irradiated with visible light in the presence of an alkyl-m-iodobenzoate dichloride to form the 9α-chloro steroid derivative. The chlorinated steroid derivative can then be hydrolized to provide a 9α-chloro steroidal alcohol and m-iodobenzoic acid. The m-iodobenzoic acid is extracted by the use of an aqueous base. The chlorinated steroidal alcohol can then be recovered and converted by conventional dehalogenation techniques to steroidal unsaturated compound having a double bond in the 9,11 position of the steroid nucleus. Alternatively, the chlorinated steroid derivative can be dehalogenation and then hydrolized.
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