- Synthetic method of drospirenone
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The invention provides a synthetic method of drospirenone. Belong to organic synthesis field. A compound having the structure shown in the formula II is obtained, 17-bit hydroxyl group is oxidized to a carbonyl group under the action of a noble metal catalyst and a persulfate, and the hydroxyl group on the III-position propyl group is oxidized into an aldehyde group, and then a hydroxyl aldehyde condensation forms a five-membered carboxylic acid lactone ring to obtain a compound having the structure shown 17 α in the formula IV 3. The compound drospirenone with the structure shown I is obtained, most of the raw materials are cheap, the high-pressure catalytic hydrogenation and is omitted, and meanwhile, the yield can reach 77% under mild reaction conditions. Drospirenone with a purity 99.6%.
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- A drospirenone and intermediate preparation method (by machine translation)
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The invention discloses a drospirenone and intermediate preparation method. Preparation method of this invention comprises the following steps: in the solvent, the compound 3 with hydrogen peroxide oxidation reaction shown below, to obtain compound 4 can be. Preparation method of this invention does not use a heavy metal reagent, reduces the toxicity of the preparation process, the use of the reagent are all conventional reagent, low cost, and is favorable for industrial large-scale production. (by machine translation)
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Paragraph 0098-0104
(2019/11/20)
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- PROCESS FOR THE PREPARATION OF DROSPIRENONE
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A process is described wherein, by employing 17a-(3-hydroxypropyl) -63,7β3;15β,16β-dimethylene-5β-androstane-3β,5,17β-triol (II) as starting product, in a single stage reaction there is obtained drospirenone, (I), whereby the reaction is achieved using gaseous oxygen as the stoichiometric oxidant in the presence of a catalytic system containing (i) TEMPO or a derivative thereof, (ii) a ferric salt (Fe3+) and (iii) NaCI. The product drospirenone is a known synthetic steroid with progestogenic, antimineralocorticoid and antiandrogenic action, that is useful for preparing pharmaceutical compositions with contraceptive action.
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Page/Page column 7; 8; 9; 10
(2014/09/03)
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- PROCESS FOR THE PREPARATION OF DROSPIRENONE
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A process is disclosed wherein, using either 17a-(3-hydroxypropyl)-6p,7p;15p,16p- dimethylene-5p-androstane-3p,5,17p-triol (II) or 3β,5^?Ι^κ^-6β,7β;15β,16β- dimethylene-5β,17α-pregnane-21,17-carbolactone (III) as starting material, through a single-step reaction it is obtained drospirenone (I), a synthetic steroid with progestogenic, antimineralocorticoid and antiandrogenic activity, useful for preparing pharmaceutical compositions with contraceptive action.
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Page/Page column 11
(2014/10/29)
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- Process for the preparation of drospirenone
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It is described a process for the preparation of Drospirenone, a synthetic steroid with progestogenic anti-mineralocorticoid and antiandrogenic activity having the formula 1 shown below, useful in the preparation of contraceptive pharmaceutical compositions, starting from 17α-(3-hydroxypropyl)-6β,7β;15β,16β-dimethylene-5β-androstan-3β,5,17β-triol.
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Paragraph 0031; 0032; 0033; 0034; 0035; 0036; 0037; 0038
(2013/06/06)
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- Process for the Preparation of Drospirenone
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A process is described, comprising the oxidation of 17α-(3-hydroxypropyl)-6β,7β,15β,16β-dimethylen-5β-androstan-3β,5,17β-triol, for the preparation of drospirenone, a synthetic steroid with progestogenic, antimineralocorticoid and antiandrogenic activity, useful for preparing pharmaceutical compositions with contraceptive action.
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Paragraph 0073-0086
(2013/03/26)
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- Stereospecific synthesis of drospirenone
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A procedure for the stereospecific synthesis of drospirenone has been developed. The key steps included the stereospecific reduction of the C 7-tertiary alcohol with ZnI2/Et3SiH, a novel mild and stereospecific tertiary alcohol reduction system, and the tandem oxidation/cyclopropanation reactions. Copyright
- Deng, Gang,Huang, Zuogang,Zhao, Xiaolong,Li, Zheng,Li, Yuanchao,Jiang, Biao
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- PROCESS FOR THE PREPARATION OF DROSPIRENONE
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It is described of a process for the preparation of drospirenone, the compound of formula 1 shown below, a synthetic steroid with progestogenic, antimineralocorticoid and antiandrogenic activity, useful for preparing pharmaceutical compositions having contraceptive action, starting from 17α-(3-hydroxypropyl)-6β,7β;15β,16β-dimethylene-5β-androstane-3β,5,17β-triοΙ.
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Page/Page column 11; 12; 13
(2013/06/06)
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- Process for the preparation of drospirenone
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A process is described, comprising the oxidation of 17α-(3-hydroxypropyl)-6β,7β,15β,16β-dimethylen-5β-androstan-3β,5,17β-triol, for the preparation of drospirenone, a synthetic steroid with progestogenic, antimineralocorticoid and antiandrogenic activity, useful for preparing pharmaceutical compositions with contraceptive action.
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Paragraph 0031-0039
(2013/03/26)
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- Biocatalytic oxidation of 1,4-diols and γ-lactols into γ-lactones: Application to chemoenzymatic synthesis of drospirenone
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Oxidation of 1-alkyl-1,4-butanediols with Acetobacter aceti MIM 2000/28 gave the corresponding γ-lactones in good yields. The biotransformation occurred with intermediate formation of γ-lactols, which are also substrates for oxidation with Acetobacter aceti MIM 2000/28, as validated by selective biotransformation of 6β,7β;15β,16β-dimethylene-3- oxo-17α-pregn-4-en-21,17-carbolactol to drospirenone.
- Romano, Diego,Contente, Martina,Granato, Tiziana,Remelli, William,Zambelli, Paolo,Molinari, Francesco
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p. 735 - 737
(2013/07/26)
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- Methods for the preparation of Drospirenone and intermediates thereof
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The invention relates to a process for the preparation of Drospirenone in high yields and purity starting from a compound of formula 2 wherein R is a hydroxyl protective group as defined in the claims, through a sequence of oxidation, deprotection, lactonization and water elimination steps, and wherein the steps of oxidation and lactonization are performed with 1,3,5-trichloro 1,3,5-triazine-2,4,6-(1H,3H,5H)-trione (trichloroisocyanuric acid, TCCA) or 1,3-dichloro-1,3,5-triazine-2,4,6-(1H,3H,5H)-trione (dichloroisocyanuric acid, DCCA) or an alkaline metal salt thereof such as the sodium salt dihydrate (DCCA sodium salt) or 1-hydroxyl,2-benziodoxol-3(777)-one 1-oxide (IBX). New synthetic intermediates useful for the synthesis of Drospirenone are disclosed, too.
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- METHODS FOR THE PREPARATION OF DROSPIRENONE AND INTERMEDIATES THEREOF
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The invention relates to a process for the preparation of Drospirenone in high yields and purity starting from a compound of formula (2) wherein R is a hydroxyl protective group as defined in the claims, through a sequence of oxidation, deprotection, lactonization and water elimination steps, and wherein the steps of oxidation and lactonization are performed with 1,3,5-trichloro 1,3,5-triazine-2,4,6-(1H,3H,5H)-trione (trichloroisocyanuric acid, TCCA) or 1,3-dichloro-1,3,5-triazine-2,4,6- (1H,3H,5H)-trione (dichloroisocyanuric acid, DCCA) or an alkaline metal salt thereof such as the sodium salt dihydrate (DCCA sodium salt) or 1-hydroxy - 1,2-benziodoxo1-3(1H)-one 1-oxide (IBX). New synthetic intermediates useful for the synthesis of Drospirenone are disclosed, too.
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- PREPARATION METHOD OF DROSPIRENONE
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The present invention discloses the preparation method of drospirenone. 3β,5-dyhydroxy-6β,7β,15β,16β-dimethylene-5β-androstane-17,20-epoxy is taken as the raw material. It is subject to oxidization of the hydroxyl at the 3rd position, ketalization of 3-ketone group, condensation reaction and deesterification to obtain carboxylic acid lactone, sulfonation of the hydroxyl at the 5th position, and deketalization and desulphonation in the reaction system of glacial acetic acid and sodium acetate to produce the 3-keto-4-alkenyl compound, thus obtaining drospirenone. The preparation method of the invention has high intensification, reaction specificity, less by-products and high yield of products in each step, thus overcoming the disadvantages of low yield and unstable quality.
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Page/Page column 4
(2013/02/27)
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- PROCESS FOR OBTAINING 17-SPIROLACTONES IN STEROIDS
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The invention relates to processes for obtaining steroids with a spirolactone group in position 17, particularly to industrially obtaining 6β,7β; 15β,16β-dimethylene-3-oxo-17α- pregn-4-ene-21,17-carbolactone, commonly known as Drospirenone, as well as to intermediates useful in said process.
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Page/Page column 56
(2010/12/31)
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- METHODS FOR THE PREPARATION OF DROSPIRENONE
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Described herein are methods of making drospirenone. Also described are intermediate compounds that may be used to synthesis drospirenone.
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Page/Page column 15
(2010/11/03)
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- Process for the preparation of Drospirenone
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A process for the preparation of Drospirenone (I) according to the following scheme wherein the substituent R is defined in the description. The process improves the product yield and purity by reducing the formation of undesired side-products and is particularly convenient for industrial-scale manufacturing.
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Page/Page column 21-22
(2009/02/10)
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- PROCESS FOR THE PREPARATION OF DROSPIRENONE
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The present invention describes a process for the preparation of drospirenone (I) using androstendione as a starting material. In particular, androstendione protected on carbonyl group in position 3 as an enol-ether is functionalized in position 16 with a sulfoxide group and the derivative thus obtained undergoes thermal elimination in alkaline to give androsta-4,15- diene-3, 17-dione (V) which is further transformed into Drospirenone (I).
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Page/Page column 8-9
(2009/06/27)
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- Epoxidation of 17-oxo-15,16-methylene steroids with sulfoxonium ylides
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A process for the epoxidation of 17-oxo-15,16-methylene steroids, in particular of drospirenone precursors, comprising the use of sulfoxonium ylides, in particular of dimethylsulfoxonium methyl ylide. The process allows to prepare in good yields 17-spiro epoxides, which can be easily transformed into 17-spironolacto-steroids.
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Page/Page column 5
(2010/11/30)
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- Epoxidation of 17-oxo-15,16-Methylene Steroids with Sulfoxonium Ylides
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A process for the epoxidation of 17-oxo-15,16-methylene steroids, in particular of drospirenone precursors, comprising the use of sulfoxonium ylides, in particular of dimethylsulfoxonium methyl ylide. The process allows to prepare in good yields 17-spiro epoxides, which can be easily transformed into 17-spironolacto-steroids.
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Page/Page column 2; 4
(2010/11/30)
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- A PROCESS FOR PREPARING DROSPIRENONE AND INTERMEDIATE THEREOF
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The present invention encompasses processes for preparing drospirenone and intermediates thereof.
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Page/Page column 18
(2009/01/20)
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- A nonclassical stereoselective semi-synthesis of drospirenone via cross-metathesis reaction
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A new synthetic approach for the construction of the spirolactone moiety of the progestin drospirenone is presented. A highly efficient cross-metathesis reaction catalyzed by Grubbs-Hoveyda second-generation catalyst (6 mol%) is employed as the key step for the introduction of the ester moiety on to the vinyl group at C17. No protecting groups are required and harmful heavy-metal-based oxidants are not used and this means that this route constitutes a valuable synthetic alternative to existing approaches. Georg Thieme Verlag Stuttgart.
- Bandini, Marco,Contento, Michele,Garelli, Andrea,Monari, Magda,Tolomelli, Alessandra,Umani-Ronchi, Achille,Andriolo, Erika,Montorsi, Mauro
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experimental part
p. 3801 - 3804
(2009/07/04)
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- Process for the production of 3-oxo-pregn-4-ene-21,17-carbolactones by the metal free oxidation of 17-(3-hydroxypropyl)-3,17-dihydroxyandrostanes
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This invention relates to processes for the production of 3-oxo-pregnane-21,17-carbolactones of formula II as well as 3-oxo-pregn-4-ene-21,17-carbolactones of formula III by the metal-free oxidation of 17-(3-hydroxypropyl)-3,17-dihydroxyandrostanes of formula I In addition, the invention relates to the dichloromethane hemisolvate of 6B,7B;15β,16β-diethylene-3-oxo-17α-pregnan-5β-ol-21,17-carbolactone (IV) as such.
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Page/Page column 6-7
(2008/06/13)
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- A PROCESS FOR THE PREPARATION OF 17-HYDROXY-6β,7β;15β,l6β-BISMETHYLENE-17α-PREGN-4-ENE-3-ONE-21-CARBOXYLIC ACID γ-LACTONE AND KEY-INTERMEDIATES FOR THIS PROCESS
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The invention relates to a process for the preparation of 17-hydroxy-6β,7β;15β,16β- bismethylene-17α-pregn-4-ene-3-one-21-carboxylic acid γ-lactone of formula (I) as well as to key- intermediates for this process.
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Page/Page column 25
(2010/11/08)
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- INDUSTRIAL PROCESS FOR THE PREPARATION OF 17-HYDROXY-6β,7β;15β,16β-BISMETHYLENE-3-OXO-17α-PREGN-4-ENE-21-CARBOXYLIC ACID γ-LACTONE AND KEY-INTERMEDIATES FOR THIS PROCESS
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The invention relates to an industrial process for the preparation of 17-hydroxy- 6β,7β;15β,16β-bismethylene-3-oxo-17α-pregn-4-ene-21-carboxylic acid γ-lactone of formula (I) , and to the key-intermediates for this process.
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Page/Page column 34-35
(2010/11/08)
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- Process for the preparation of drospirenone
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A process is described for preparing drospirenone, a synthetic steroid with progestogenic, antimineralocorticoid and antiandrogenic activity, useful for the preparation of pharmaceutical compositions with contraceptive action, starting from 5,6beta-epoxy-7beta-hydroxy-15beta,16beta-methylene-3beta-pivaloyloxy-5beta-androstan-17-one.
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Page/Page column 9
(2008/06/13)
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- A process for the preparation of drospirenone
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A process is described for preparing drospirenone, a synthetic steroid with progestogenic, antimineralocorticoid and antiandrogenic activity, useful for the preparation of pharmaceutical compositions with contraceptive action, starting from 5,6β-epoxy-7β-hydroxy-15β,16β-methylene-3β-pivaloyloxy-5β-androstan-17-one.
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Page/Page column 5; 12; 15
(2010/02/13)
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- Cyclodextrin-drospirenone inclusion complexes
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Described are inclusion complexes formed between cyclodextrin and drospirenone. In a specific embodiment of the invention, the cyclodextrin is β-cyclodextrin. The invention further relates to methods of providing such an inclusion complex, and to the use of said inclusion complex for improving the solubility of drospirenone, for providing pharmaceutical compositions, for use as a medicament in the treatment of symptoms associated with menopause and in female contraception.
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