CH297193A - Process for the preparation of 5,7,9-pregnatriene-3(B)-ol-20-one. - Google Patents
Process for the preparation of 5,7,9-pregnatriene-3(B)-ol-20-one.Info
- Publication number
- CH297193A CH297193A CH297193DA CH297193A CH 297193 A CH297193 A CH 297193A CH 297193D A CH297193D A CH 297193DA CH 297193 A CH297193 A CH 297193A
- Authority
- CH
- Switzerland
- Prior art keywords
- pregnatriene
- acetate
- heating
- pregnadiene
- preparation
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 3
- 238000002360 preparation method Methods 0.000 title description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 12
- 150000001875 compounds Chemical class 0.000 claims description 8
- 238000010438 heat treatment Methods 0.000 claims description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 5
- 238000002844 melting Methods 0.000 claims description 4
- 230000008018 melting Effects 0.000 claims description 4
- DNIAPMSPPWPWGF-GSVOUGTGSA-N (R)-(-)-Propylene glycol Chemical compound C[C@@H](O)CO DNIAPMSPPWPWGF-GSVOUGTGSA-N 0.000 claims description 3
- 230000001747 exhibiting effect Effects 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- BRMYZIKAHFEUFJ-UHFFFAOYSA-L mercury diacetate Chemical compound CC(=O)O[Hg]OC(C)=O BRMYZIKAHFEUFJ-UHFFFAOYSA-L 0.000 claims description 3
- 239000007787 solid Substances 0.000 claims 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- 229930182558 Sterol Natural products 0.000 description 6
- 235000003702 sterols Nutrition 0.000 description 6
- FUFLCEKSBBHCMO-UHFFFAOYSA-N 11-dehydrocorticosterone Natural products O=C1CCC2(C)C3C(=O)CC(C)(C(CC4)C(=O)CO)C4C3CCC2=C1 FUFLCEKSBBHCMO-UHFFFAOYSA-N 0.000 description 5
- MFYSYFVPBJMHGN-ZPOLXVRWSA-N Cortisone Chemical compound O=C1CC[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 MFYSYFVPBJMHGN-ZPOLXVRWSA-N 0.000 description 5
- MFYSYFVPBJMHGN-UHFFFAOYSA-N Cortisone Natural products O=C1CCC2(C)C3C(=O)CC(C)(C(CC4)(O)C(=O)CO)C4C3CCC2=C1 MFYSYFVPBJMHGN-UHFFFAOYSA-N 0.000 description 5
- 229960004544 cortisone Drugs 0.000 description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 150000003432 sterols Chemical class 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 229910052739 hydrogen Inorganic materials 0.000 description 3
- 239000001257 hydrogen Substances 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 125000004185 ester group Chemical group 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 239000003208 petroleum Substances 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- -1 sterol esters Chemical class 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- WRYNUJYAXVDTCB-UHFFFAOYSA-M acetyloxymercury Chemical compound CC(=O)O[Hg] WRYNUJYAXVDTCB-UHFFFAOYSA-M 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 238000005194 fractionation Methods 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- TUJKJAMUKRIRHC-UHFFFAOYSA-N hydroxyl Chemical compound [OH] TUJKJAMUKRIRHC-UHFFFAOYSA-N 0.000 description 1
- 125000000468 ketone group Chemical group 0.000 description 1
- ULSIYEODSMZIPX-UHFFFAOYSA-N phenylethanolamine Chemical compound NCC(O)C1=CC=CC=C1 ULSIYEODSMZIPX-UHFFFAOYSA-N 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 201000003068 rheumatic fever Diseases 0.000 description 1
- 229930195734 saturated hydrocarbon Natural products 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J7/00—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J75/00—Processes for the preparation of steroids in general
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
Procédé de préparation de d',',9-prégnatriène-3(p)-ol-20-one. La présente invention concerne la prépa ration de stérols et d'esters de stérols de la série du. cvelopentanodiméthv lpolv hv drophé- iianthrène.
Récemment, certains stérols et esters de stérols de la série du cyclopentanodiméthyl.- Irolvhvdrophénanthrène, en particulier ceux comportant, une chaîne latérale en position 17 cl. des groupements céto en positions 3 et 17., ont. rencontré un grand intérêt en médecine. On a. trouvé que l'un de ces composés, que l'on rencontre naturellement dans l'écorce .sur-
EMI0001.0011
rénale et que l'on désigne ordinairement par cortisone, présente une activité élevée dans le traitement de l'arthrite, de la fièvre rhuma tismale et d'autres états pathologiques voi sins.
La désignation chimique de la cortisone est J4-prégnène-17a, \?1-diol-3,11,20-trione. On a également signalé des composés présentant une structure chimique voisine de la. cortisone comme ayant une activité analogue à celle de la cortisone.
La titulaire a trouvé des stérols et esters de stérols nouveaux présentant les formules I et II suivantes:
EMI0002.0001
Dans les formules I et II ci-dessus et dans la formule III ci-après, R représente de l'hy drogène ou un radical acyle ou aroyle, R' de l'hydrogène ou un radical hydroxyle et R" de l'hydrogène ou un radical hydroxyle ou acyloxy.
Les nouveaux composés de formule I sont obtenus en faisant. réagir, par chauffage, le _J5#7-prégnadiène correspondant de formule II
EMI0002.0010
avec de la N-bromosuccinimide et une amine tertiaire en présence d'un hydrocarbure sa turé comme solvant. Dans le produit obtenu, on peut hydrolyser les groupements esters en position 3 et/ou 21.
Le présent brevét a pour objet un procédé de préparation d'un des nouveaux composés de formule 1, savoir le 45.7,9-prégnatriène- 3(f)-ol-20-one; ce procédé est caractérisé en ce que l'on fait réagir, par chauffage, de avec de l'acétate mercurique et de l'acide acé tique en présence d'un alcool aliphatique infé rieur. Dans le produit obtenu, on peut hydro lyser les groupements esters en position 3 et/ou 21.
Les composés présentant. la formule Il sont obtenus en faisant réagir, par chauffage, le 7,8-dihydroprégnadiène correspondant de formule III: l'acétate de A5#7-prégnadiène-3 (fl)-ol-20-one avec de 1-'acétate mercurique et de l'acide acé tique en présence d'un alcool aliphatique inférieur et qu'on hydrolyse le produit obtenu.
Le chauffage est effectué, de préférence, à, une température comprise entre 50 et l25 C. La d5,7,9-prégnatriène-3(f)-ol-20-one ainsi obtenue présente un point de fusion de 221 à 225 C. Ce composé est utilisable comme pharmaceutique et comme intermédiaire dans la préparation de composés présentant une activité analogue à celle de la cortisone.
L'exemple suivant montre comment on peut. réaliser l'invention.
<I>Exemple:</I> On dissout clans de l'éthanol 820 mg d'acétate de ds.7-prégnadiène-3(/8)-ol-20-one et on traite la solution chaude par une solution chaude de '',4 g d'acétate mercurique dans de L'alcool contenant 1 cms d'acide acétique gla- eial. Le volume total d'alcool est de 50 cm3. On soumet le mélange au reflux pendant une heure et demie, on filtre à chaud pour sépa rer l'acétate mercureuX et on évapore le fil trat sous pression réduite. On extrait le résidu par le benzène, on filtre et on évapore la so lution.
Par recristallisation dans le méthanol, on obtient, l'acétate de 45.7.9-prégnatriène- 3(p)-ol-20-one chi point. de fusion 143-145 C.
EMI0003.0015
On soumet au reflux pendant 2 heures un mélange de 3,7 g d'acétate de 45,7,9_prégna- triène-3 (fl)-ol-20-one, 3,0 g de carbonate de potassium et 75 cm3 de méthanol, on le re froidit et on le traite par de l'eau. On re cueille les cristaux résultants et on les traite par de l'eau et du méthanol.
On obtient 2,7 g de cristaux présentant un point de fusion de 220-221 5 C. Par recristallisation et frac tionnement. (liqueurs mères comprises) à l'aide de benzène-méthanol, chloroforme-éther de pétrole, acétone-éther de pétrole et acétone, on obtient 1,52 g de d5>7>9-prégnatriène-3(fl)- ol-20-one présentant un point de fusion de 221-225 C.
EMI0003.0025
A process for preparing d ',', 9-pregnatriene-3 (p) -ol-20-one. The present invention relates to the preparation of sterols and sterol esters of the series du. cvelopentanodiméthv lpolv hv drophéiianthrene.
Recently, certain sterols and sterol esters of the cyclopentanodimethyl-Irolvhvdrophenanthrene series, in particular those having a side chain at the 17 cl position. keto groups in positions 3 and 17, have. met great interest in medicine. We have. found that one of these compounds, which occurs naturally in the bark on-
EMI0001.0011
renal, commonly referred to as cortisone, shows high activity in the treatment of arthritis, rheumatic fever and other related disease states.
The chemical designation of cortisone is J4-pregnene-17a, \? 1-diol-3,11,20-trione. Compounds have also been reported with a chemical structure similar to. cortisone as having an activity analogous to that of cortisone.
The licensee found new sterols and esters of sterols with the following formulas I and II:
EMI0002.0001
In formulas I and II above and in formula III below, R represents hydrogen or an acyl or aroyl radical, R 'is hydrogen or a hydroxyl radical and R "is hydrogen or a hydroxyl or acyloxy radical.
The new compounds of formula I are obtained by making. reacting, by heating, the corresponding _J5 # 7-pregnadiene of formula II
EMI0002.0010
with N-bromosuccinimide and a tertiary amine in the presence of a saturated hydrocarbon as solvent. In the product obtained, it is possible to hydrolyze the ester groups in position 3 and / or 21.
The present patent relates to a process for preparing one of the new compounds of formula 1, namely 45.7,9-pregnatriene-3 (f) -ol-20-one; this process is characterized in that one reacts, by heating, with mercuric acetate and acetic acid in the presence of a lower aliphatic alcohol. In the product obtained, the ester groups in position 3 and / or 21 can be hydrolysed.
The compounds exhibiting. formula II are obtained by reacting, by heating, the corresponding 7,8-dihydropregnadiene of formula III: acetate of A5 # 7-pregnadiene-3 (fl) -ol-20-one with 1-mercuric acetate and acetic acid in the presence of a lower aliphatic alcohol and the product obtained is hydrolyzed.
The heating is preferably carried out at a temperature between 50 and 125 C. The d5,7,9-pregnatriene-3 (f) -ol-20-one thus obtained has a melting point of 221 to 225 C. This compound can be used as a pharmaceutical and as an intermediate in the preparation of compounds exhibiting an activity analogous to that of cortisone.
The following example shows how we can. realize the invention.
<I> Example: </I> 820 mg of ds.7-pregnadiene-3 (/ 8) -ol-20-one acetate are dissolved in ethanol and the hot solution is treated with a hot solution of '', 4 g of mercuric acetate in alcohol containing 1 cms of ice acetic acid. The total alcohol volume is 50 cm3. The mixture is refluxed for 1.5 hours, filtered hot to separate the mercury acetate and the treated wire evaporated under reduced pressure. The residue is extracted with benzene, filtered and the solution evaporated.
By recrystallization from methanol, 45.7.9-pregnatriene-3 (p) -ol-20-one chi point acetate is obtained. 143-145 C.
EMI0003.0015
A mixture of 3.7 g of 45,7,9_prregnatriene-3 (fl) -ol-20-one acetate, 3.0 g of potassium carbonate and 75 cm3 of methanol is refluxed for 2 hours. , it is cooled again and it is treated with water. The resulting crystals are collected and treated with water and methanol.
2.7 g of crystals with a melting point of 220-221 5 C. are obtained by recrystallization and fractionation. (mother liquors included) using benzene-methanol, chloroform-petroleum ether, acetone-petroleum ether and acetone, 1.52 g of d5> 7> 9-pregnatriene-3 (fl) - ol- are obtained 20-one having a melting point of 221-225 C.
EMI0003.0025
Claims (1)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US297193XA | 1950-09-26 | 1950-09-26 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH297193A true CH297193A (en) | 1954-03-15 |
Family
ID=21850507
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH297193D CH297193A (en) | 1950-09-26 | 1951-09-25 | Process for the preparation of 5,7,9-pregnatriene-3(B)-ol-20-one. |
Country Status (1)
| Country | Link |
|---|---|
| CH (1) | CH297193A (en) |
-
1951
- 1951-09-25 CH CH297193D patent/CH297193A/en unknown
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP0051023A1 (en) | Derivatives of the benzoyl and alpha hydroxybenzyl-phenyl osides family, method for their preparation and their therapeutic application | |
| MC1417A1 (en) | TETRASUBSTITUTED BENZENE DERIVATIVES | |
| EP0074873A1 (en) | Derivatives of 3-phenoxy-3-propanol, their preparation and their therapeutic use | |
| BE779775A (en) | DERIVATIVES OF UREA, METHOD FOR PREPARING THEM AND THEIR APPLICATIONS | |
| FR2459219A1 (en) | ALKANOIC ACID DERIVATIVES | |
| US2540307A (en) | 3, 4-diethoxymandelic acid and process for preparing same | |
| EP0002401B1 (en) | Derivatives of naphthalene, process for their preparation and their therapeutic application | |
| EP0071500A1 (en) | Process for the preparation of 4-aminobutyramide | |
| CH450401A (en) | Process for preparing new colchicium derivatives | |
| CH334310A (en) | Process for the preparation of N-deacetyl-thiocolchiceins | |
| DE2246867A1 (en) | TETRAHYDROXY-BICYCLO- SQUARE BRACKET ON 3.3.0 SQUARE BRACKET TO -OCTANE | |
| BE884145R (en) | NEW INDOLIC COMPOUNDS | |
| BE707409A (en) | ||
| CH426781A (en) | Process for the conversion of 1,2,3,4-tetrahydro-anthracene compounds into 1,2,3,4,4a, 5,12,12a-octahydronaphtacene compounds | |
| CH371798A (en) | Process for the preparation of novel 2-piperidyl phenylcarbinol esters | |
| CH301958A (en) | Process for the preparation of 7-androstene-3B,17B-diol. | |
| CH356766A (en) | Process for the preparation of diesters 16a, 21 of the oxide 9ss, 11s of 16a, 1ma, 21-triol-3,20 / diketo-4-pregnene | |
| CH408953A (en) | Process for the preparation of new substituted carbazates | |
| BE837320A (en) | 3-AMINO-1,2-PROPANODIOL ETHER DERIVATIVES | |
| CH402842A (en) | Process for the preparation of new heparin derivatives | |
| FR2460945A2 (en) | 6-Chloro-2,4,4-tri:methyl-4H-1,3-benzodioxin-2-carboxylic acid - useful in treatment of hyperlipidaemia, angina and cardiac insufficiency | |
| Dauben et al. | The Synthesis of 2-Hydroxy-3-[3'-cis-(4-hydroxycyclohexyl)-propyl]-1, 4-naphthoquinone | |
| BE565010A (en) | ||
| CH529744A (en) | Phenylacetic acid derivs as antiinflamma- | |
| CH330478A (en) | Process for the preparation of novel thioderivatives of colchiceines |