37413-91-5Relevant articles and documents
Optimization of the synthesis of a key intermediate for the preparation of glucocorticoids
Jouve, Romain,Thery, Vincent,Ducki, Sylvie,Helfenbein, Julie,Thiery, Jean-Christophe,Job, Aurélie,Picard, Elodie,Mallet, Christophe,Ripoche, Isabelle,Bennis, Khalil
, p. 14 - 21 (2018)
A short and efficient synthesis, based on a one-step double elimination, of a key intermediate in the synthesis of various glucocorticosteroids has been developed. This method can be carried out on large scale for further industrial applications. The synthesis allowed us to identify a novel prednisolone derivative 10 and its anti-inflammatory activity was determined in an in vivo model of inflammation. In order to understand the regioselectivity of the double elimination under various conditions, mechanistic studies were undertaken and confirmed the experimental results. We also propose a mechanism for the formation of the new steroid 10 studied by molecular modeling.
An efficient procedure for the synthesis of 21-acetoxypregna-1,4,9(11),16-tetraene-3,20-dione
Huy, Luu D.,Diep, Nguyen T.,Vu, Tran K.,Savinova, Tatiana S.,Donova, Marina V.
, p. 225 - 231 (2020/04/27)
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.
Preparation method of tetraene acetate
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Paragraph 0066-0086, (2019/12/25)
The invention discloses a preparation method of tetraene acetate. The preparation method of tetraene acetate comprises a step of subjecting a compound 2 as described in the specification, a free radical type halogenating reagent, sulfur dioxide and an acid-binding agent to a reaction in an organic solvent so as to obtain a compound 1 as described in the specification, i.e., tetraene acetate. According to the preparation method, easily and commercially available prednisolone low in price is used as a starting raw material, hydroxyl groups of two different configurations are simultaneously eliminated in the one-step reaction, and intracyclic alkene is formed; and the method is reduced in reaction steps, mild in reaction conditions, simple in aftertreatment, high in yield, high in the chemical purity of a crude product and suitable for industrial production.
Method for preparing tetraene acetate
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Paragraph 0021-0023; 0026; 0029; 0032; 0035; 0038, (2019/01/07)
The invention provides a method for preparing tetraene acetate. The method comprises the steps of subjecting a raw material, i.e., 17-ynepregna-1,4,9(11)-trien-3-one-17-hydroxyl acetate to a reactionin an organic solvent in the presence of a catalyst, i.e., palladium acetate and an oxidant, i.e., p-benzoquinone under the protection of inert gas so as to produce an intermediate, i.e., 18-hydroxylpregna-1,4,9(11),17-tetraen-3,19-dion-18-acetate, and carrying out treatment by using 1,8-diazabicycloundec-7-ene, thereby obtaining the tetraene acetate (21-hydroxylpregna-1,4,9(11),16-tetraen-3,20-dion-21-acetate)According to the method provided by the invention, the use of palladium chloride, copper chloride and oxygen is avoided, the corrosion to equipment is low, and meanwhile, the purity of the product is improved. The method has the advantages of being safe and efficient, being simple and convenient in operation, being satisfactory for industrial production, and the like and has a relatively high application value.
Preparation method of tetraene acetate
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, (2018/05/16)
The invention belongs to the technical field of preparation of a steroid hormone drug intermediate, and in particular relates to a preparation method of tetraene acetate. The tetraene acetate is prepared from 1,4,9(11)-triene-androstane-3,17-dione as a raw material sequentially by reaction steps of ethynylation, esterification, bromination and debromination reaction and displacement and elimination reaction, no precious metal catalyst is used in the method, the raw material is easily available, the cost is low, and the reaction is easy to operate. The method is suitable for industrial production. After refining the mass yield by the whole route is more than 88%, and the purity is more than 99%.
Preparation method of delta 16 steroid
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Paragraph 0077; 0078; 0079; 0080; 0081, (2016/10/07)
The invention relates to a preparation method of a delta 16 steroid. At the atmosphere of protective gas, a compound of a formula II, an oxidizing agent and sulfur dioxide are subjected to a reaction in an organic solvent, the reaction temperature ranges from minus 50 DEG C to 0 DEG C, and the reaction time is 1.5-2.5 h to obtain a delta 16 steroid I, wherein R1 is selected from H, halogen and acyloxy or hydroxide of C1-5; R2 is selected from alkyl of alpha C1-3 and alkyl or H of beta C1-2; R3 is selected from H, alkyl of alpha C1-3, alkyl of beta C1-2, alpha halogen or beta halogen; R4 and R5 are equal to H or double bonds; R7 is selected from H, and R6 is selected from H, alkyl of C1-3 or acyloxy of C1-5; or R6 and R7 are equal to double bonds. According to the preparation method of the delta 16 steroid, the 17-bit hydroxide compound of the formula II is used as raw materials, and the compound of the formula II is industrially produced and is easy to obtain; the preparation method is mild in reaction condition, no high-temperature strong base or strong acid is needed, fewer by-products are produced, the product yield and purity are high, the yield reaches more than 90%, and the purity reaches more than 93%.
Method for preparing tetraene acetate and derivatives thereof
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Paragraph 0109, (2016/12/01)
The invention relates to a method for preparing tetraene acetate and derivatives thereof. The method comprises the steps of obtaining a compound II through etherification reaction of a compound I and an etherification agent in the atmosphere of protective gases, obtaining a compound III through addition reaction of the compound II and a reagent A under the action of strong base and hydrolysis and elimination reaction of the compound II and the reagent A in the presence of an acid solution, obtaining a compound IV through substitution reaction and rearrangement reaction of the compound III and acetate, and conducting 1 position dehydrogenation and 2 position dehydrogenation on the compound IV to obtain the tetraene acetate and derivatives thereof. According to the method, the compound I is taken as the raw material and subjected to carbonyl etherification, addition, hydrolysis, elimination, rearrangement and dehydrogenation reaction to obtain the product, the raw material compound I is easy to obtain, cost is low, no precious metal is needed during preparation, reaction conditions are easy to control, operation is convenient, the method is suitable for large-scale industrial production, and the obtained tetraene acetate is an important intermediate for synthesis of dexamethasone, budesonide, betamethasone and other steroidal drugs.
Expedient synthesis of 17α,21-dihydroxy-9β,11β-epoxy- 16αmethylpregna- 1,4-diene-3,20-dione 21-acetate from prednisolone utilising a novel Mattox rearrangement
Hulcoop, David G.,Shapland, Peter D.P.
, p. 1281 - 1287 (2013/11/06)
A six step transformation of prednisolone to 17a,21-dihydroxy-9b,11b-epoxy- 16a-amethylpregna-1,4- diene-3,20-dione 21-acetate has been achieved in 13% unoptimised yield. Novel conditions for effecting a Mattox rearrangement and double dehydration of prednisolone were identified. Enhanced knowledge on the oxidation of silyl D19,20-enol ethers and structural factors that impact the success of the oxidation are also presented.
