67392-87-4

Basic information

• Product Name: Drospirenone
• Synonyms: ,5’(2h)-dione,1,3’,4’,6,7,8,9,10,11,12,13,14,15,16,20,21-hexadecahydro-10,13-;1,2-dihydrospirorenone;15-beta,16-beta-dimethylene-3-oxo-17-alpha-pregn-4-ene-21,17-c;ZK 3059;DROSPIRENONE INTERMEDIATE;DEHYDROSPIRORENONE;6b,7b:15b,16b-Dimethylen-3-oxo-17a-pregn-4-ene-21,17-carbolactone;6,7,15,16-Dimethylene-3-oxo-4-androstene-[17(-1’)-spiro-5’]perhydrofuran-2’-one
• CAS NO: 67392-87-4
• Molecular Formula: C₂₄H₃₀O₃
• Molecular Weight: 366.4932
• EINECS: 266-679-2
• Product Categories: Intermediates & Fine Chemicals;Pharmaceuticals;Steroids;Steroid and Hormone;REBETOL;Other APIs
• Mol File: 67392-87-4.mol

Chemical Properties

• Melting Point: 196-200°C
• Boiling Point: 552.2 °C at 760 mmHg
• Flash Point: 241.6 °C
• Appearance: white to tan/
• Density: 1.26 g/cm³
• Vapor Pressure: 3.07E-12mmHg at 25°C
• Refractive Index: 1.61
• Storage Temp.: -20°C Freezer
• Solubility: DMSO: ≥15
• CAS DataBase Reference: Drospirenone(CAS DataBase Reference)
• NIST Chemistry Reference: Drospirenone(67392-87-4)
• EPA Substance Registry System: Drospirenone(67392-87-4)

Safety Data

• Hazard Codes: T
• Statements: 60
• Safety Statements: 36/37
• WGK Germany: 3
• RTECS: WH1299000
• Hazardous Substances Data: 67392-87-4(Hazardous Substances Data)

Usage

Natural progesterone

Drospirenone is the only progesterone that has the characteristics similar to the natural progesterone currently, its structure is more like that of the natural progesterone compare with the structure of the progesterone contained in the traditional oral contraceptives. Except the effect of anti-androgen, drospirenone has the role of anti-mineralocorticoid which can prevent water and sodium retain in the body. Not only it has the a great effectivenes of contraception, there are also many good impacts on women's health like reducing the acne, making the skin more smooth and controling the weight efficaciously. Information on the use of oral contraceptives, drospirenone, side effects and other information edited by lookchem maggie.

Side effects of human estrogen

Drospirenone is a new synthetic progestin designed to mimic the effects of progesterone, it is the preogesterone which the pharmacological properties is closet to that of the natural progesterone, its also has the advantages of both salt corticosteroids and anti-androgen. As a birth control hormones， Its can reduce the risk of pregnency by imitating progesterone, and increasing the levels of hormones. Therefore drospirenone is promoted as an effective contraception. However, since it has entered the market, drospirenone displays a negative impact on the female estrogen. When two hormones are mixed together, it would bring some bad influence to people. When drospirenone reacts with estrogen, it can cause the blood thicken. It looks not like a big problem, but the blood clotting would lead to the formation of the thrombosis. The gore forming in the veins can impede blood flow or even plug in some vital organs like the heart, brain and lungs etc when it flowing. The thrombosis would Interference the heart from receiving blood which can cause a heart attack. If it affect the blood flow in brain, it would resulting in a stroke. There is a possibility of side effects for any women who take the drospirenone, but the people who is obesity, smoking, depression, and have some diseases like the diabetes and high blood pressure are more likely to form the thrombosis when they take the contraception contained the drospirenone.

Originator

Schering AG (Germany)

Manufacturing Process

2.75 g of trimethyl sulfoxonium iodide is stirred in 57 ml of dimethyl sulfoxide with 341 mg of 80% sodium hydride oil suspension for 2 h at room temperature. The almost clear solution is combined under nitrogen with 2.0 g of 15α,16α-methylene-3-oxo-4,6-androstadiene-[17(β-1')-spiro- 5']perhydrofuran-2'-one and agitated for 24 h at room temperature. The mixture is then stirred into ice water, the thus-obtained precipitate is filtered off, washed with water, and taken up in methylene chloride. After drying and evaporation, the residue is purified by repeated preparative layer chromatography, thus obtaining 520 mg of 6β,7β,15α,16α-dimethylene-3-oxo- 4-androstene-[17(β-1')-spiro-5']perhydrofuran-2'-one (drospirenone).

Therapeutic Function

Aldosterone antagonist

Biochem/physiol Actions

Drospirenone is a fourth-generation progestin that has antimineralocorticoid, and antiandrogenic activity in addition to potent progestogenic activity. In two recent studies drospirenone appeared to double the risk of venous thromboembolism compared to levonorgestrel, although other studies found little added risk.

InChI:InChI=1/C24H30O3/c1-22-6-3-12(25)9-17(22)13-10-14(13)20-16(22)4-7-23(2)21(20)15-11-18(15)24(23)8-5-19(26)27-24/h9,13-16,18,20-21H,3-8,10-11H2,1-2H3/t13-,14+,15-,16+,18+,20-,21+,22-,23+,24+/m1/s1

Upstream product

• 82543-18-8 17α-(3-hydroxypropyl)-6β,7β;15β,16β-dimethylene-5β-androstane-3β,5,17β-triol 
• 90457-65-1 3-(17β-hydroxy-6β,7β;15β,16β-dimethylene-3-oxo-4-androstene-17β-yl)propionic acid γ-lactone 
• 1015063-83-8 C₂₅H₃₀O₅ 
• 67372-65-0 3β-hydorxy-15β,16β-methylene androst-5-ene-17-one 
• 82543-16-6 (2S,4aR,4bS,6aS,7aS,8aS,8bS,8cR,8dR,9aR,9bR)-2,9b-dihydroxy-4a,6a-dimethyloctadecahydro-7H-cyclopropa[4,5]cyclopenta[1,2-a]cyclopropa[l]phenanthren-7-one 
• 82543-15-5 3β,5-dihydroxy-15β,16β-methylene-5β-androst-6-en-17-one 
• 82543-07-5 3β,7β-dihydroxy-15β,16β-methylene-5-androsten-17-one 
• 82543-17-7 17α-(3-hydroxy-1-propinyl)-6β,7β;15β,16β-dimethylene-5β-androstane-3β,5,17β-triol 
• 82543-14-4 5-hydroxy-15β,16β-methylene-3β-pivaloyloxy-5β-androst-6-en-17-one 
• 82544-13-6 5,6β-epoxy-7β-hydroxy-15β,16β-methylene-3β-pivaloyloxy-5β-androstan-17-one 
• 82543-13-3 7α-chloro-5,6β-epoxy-15β,16β-methylene-3β-pivaloyloxy-5β-androstan-17-one 
• 82543-09-7 7β-hydroxy-15β,16β-methylene-3β-pivaloyloxy-5-androsten-17-one 
• 863329-70-8 6β,7β;15β,16β-dimethylene-5β-hydroxy-3-oxo-17α-pregn-21,17-carbolactol 
• 863329-71-9 6β,7β;15β,16β-dimethylene-3-oxo-17α-pregn-4-en-21,17-carbolactol 

Downstream Products

• 74220-07-8 Spirorenone 
• 932388-89-1 7β-chloromethyl-15β,16β-methylene-3-oxo-17β-pregn-4-ene-21,17-carbolactone 
• 932388-89-1 7β-chloromethyl-15β,16β-methylene-3-oxo-17α-pregn-4-ene-21,17-carbolactone 

Relevant articles and documents

Synthetic method of drospirenone

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%.

A drospirenone and intermediate preparation method (by machine translation)

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)

PROCESS FOR THE PREPARATION OF DROSPIRENONE

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.

PROCESS FOR THE PREPARATION OF DROSPIRENONE

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.

Biocatalytic oxidation of 1,4-diols and γ-lactols into γ-lactones: Application to chemoenzymatic synthesis of drospirenone

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.

Stereospecific synthesis of drospirenone

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

Process for the preparation of drospirenone

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.

Process for the Preparation of Drospirenone

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.

PROCESS FOR THE PREPARATION OF DROSPIRENONE

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.

Process for the preparation of drospirenone

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.