- 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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- Non-hormonal steroid modulators of NF-κβ for treatment of disease
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The present invention relates to compounds and methods which may be useful as treatments of diseases.
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Page/Page column 38-39
(2019/11/18)
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- Anecortave acetate preparation method
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The invention discloses an anecortave acetate preparation method which includes, in protection of nitrogen gas, suspending 17-hydroxy-4,9(11)-diene-3,20-diketone-21-halide in a specific solvent, carrying out substitution reaction on presence of acetate and a phase transfer catalyst, and carrying out elutriation and solvent refining to obtain anecortave acetate. With the phase transfer catalyst, reaction time of the conventional process is shortened, and production cost is lowered. Besides, the anecortave acetate preparation method achieves high reaction yield, needs mild reaction condition, has high operability, and is a convenient industrial preparation process.
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Paragraph 0032; 0034; 0038; 0039; 0041; 0045; 0048; 0050
(2018/07/30)
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- Synthesis method of 17-site side chain of steroidal drug
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The invention provides a synthesis method of 17-site side chain of a steroidal drug. The method is characterized in that a compound I is taken as a starting material, and the 17-site side chain of thesteroidal drug is synthesized by means of reactions such as a nucleophilic reaction, an esterification reaction, an elimination reaction and an oxidation reaction; compared with the traditional technology, the method adopts 3-hydroxypropionitrile and a cyano group, and does not use a material such as acetone nitrile alcohol or sodium cyanide with violent toxicity, thus being safer and higher in environmental protection property; furthermore, all the steps of reactions are relatively easy to implement; the method is high in yield and purity as well as more economical and safe in production, thus being more suitable for industrial production.
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Paragraph 0076; 0078; 0087; 0088
(2018/06/26)
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- Method for preparing difluprednate
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The invention discloses a method for preparing difluprednate. The difluprednate is synthesized from a raw material hydrocortisone-21-acetate. The raw material is readily available and relatively low-cost. A synthesis line comprising eight steps is relatively short, cost is relatively low, reaction conditions are mild, yield is relatively high, and industrial production is convenient.
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Paragraph 0042; 0043
(2017/08/29)
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- Preparation method of hydrocortisone acetate
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The invention relates to a preparation method of hydrocortisone acetate. A steroid raw material compound A is subjected to alkynylation reaction, solid-supported catalytic oxidation reaction and addition reaction to prepare hydrocortisone acetate. According to the method, the starting material is a basic steroid raw material, the source is easy to obtain, the cost is low, the synthesis procedure is short, all steps of reaction are relatively easy to implement, the yield is high, the catalyst and the carrier can be recycled, dangerous and toxic materials such as bromine are avoided, the dependence on high-end equipment is greatly reduced, the environment pollution is reduced, the production is more economic and environmental-friendly and safer, and the preparation method of the hydrocortisone acetate is more suitable for industrial production.
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- NON-HORMONAL STEROID MODULATORS OF NF-KAPPA BETA FOR TREATMENT OF DISEASE
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The present invention relates to compounds and methods which may be useful as treatments of diseases.
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Paragraph 0222-0224
(2017/01/19)
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- NON-HORMONAL STEROID MODULATORS OF NF-KB FOR TREATMENT OF DISEASE
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The present invention relates to compounds and methods which may be useful as treatments of neuromuscular diseases such as muscular dystrophy, and as inhibitors of NF-κB for the treatment or prevention of muscular wasting disease, including muscular dystrophy.
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Paragraph 0151; 0152; 0153
(2015/09/23)
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- NON-HORMONAL STEROID MODULATORS OF NF-KB FOR TREATMENT OF DISEASE
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The present invention relates to compounds and methods which may be useful as treatments of diseases.
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Paragraph 0199
(2013/06/27)
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- NON-HORMONAL STEROID MODULATORS OF NF-?B FOR TREATMENT OF DISEASE
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The present invention relates to compounds and methods which may be useful as treatments of neuromuscular diseases such as muscular dystrophy, and as inhibitors of NF-?Β for the treatment or prevention of muscular wasting disease, including muscular dystrophy.
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Page/Page column 49-50
(2011/10/31)
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- 17 α-chloroethynyl pregnane derivatives
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Known pregnane derivatives are prepared by esterificiation of known androstane derivatives to give new ester of Formula III STR1 wherein in each case symbolizes a single bond or a double bond, n is 1 or 2, R1 is hydrogen or methyl, R2 is hydrogen or formyl, and R3 is chlorine, hydroxy or an alkanoyloxy group of up to 6 carbon atoms, and reaction of the latter with Ag(I) and formic acid.
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- Process and intermediates for the preparation of 17 alphahydroxyprogesterones and corticoids from an enol steroid
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This invention discloses an improved process for the production of corticoids from 17α-hydroxy steroids utilizing peroxymonosulfate.
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- Δ16-20-Keto steroid conversion to 17α-hydroxy-20-keto steroids
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Δ16-20-keto steroids (I) are converted to 17α-hydroxy-20-keto steroids (III) in 2 steps, hydrosilylation followed by peracid oxidation.
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- Corticosteroids from 17-keto steroids via 20-cyano-Δ17 (20)-pregnanes
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The process of the present invention transforms 17-keto steroids (I) to the corresponding corticoids (IV) in three steps.
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- Metallated halogenated acetylene corticoid synthesis
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A process for the preparation of corticoids (IX) which comprises reacting a 17-keto steroid (I) with a metallated halogenated acetylene (II) followed by reaction with a sulfenylating agent (IV) and C17 side chain rearrangement.
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- Preparation of corticoids from 17-keto steroids
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A process for the preparation of corticoids (XI) which comprises reacting a protected 17-keto steroid (II) with a metallated 1,2-dihaloethene (III).
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- Process for the preparation of 17α-hydroxyprogesterones and corticoids from androstenes
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This invention discloses a general process for the production of corticoids from androstenes. This invention provides an economically viable alternative synthesis of 17α-hydroxyprogesterones and the corticoids.
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