CH246178A - Process for the preparation of a new compound of the cyclopentano-polyhydrophenanthrene series. - Google Patents
Process for the preparation of a new compound of the cyclopentano-polyhydrophenanthrene series.Info
- Publication number
- CH246178A CH246178A CH246178DA CH246178A CH 246178 A CH246178 A CH 246178A CH 246178D A CH246178D A CH 246178DA CH 246178 A CH246178 A CH 246178A
- Authority
- CH
- Switzerland
- Prior art keywords
- geto
- acid
- cyclopentano
- methyl ester
- preparation
- Prior art date
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J9/00—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of more than two carbon atoms, e.g. cholane, cholestane, coprostane
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J3/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by one carbon atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J5/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane and substituted in position 21 by only one singly bound oxygen atom, i.e. only one oxygen bound to position 21 by a single bond
-
- 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
Description
Verfahren zur Herstellung einer neuen Verbindung der Cyclopentano- polyhydrophenanthrenreihe. Es wurde gefunden, dass man zu einer im Ring C ungesättigten Verbindung der Cyclo- pentanopolyhydrophenanthrenreihe gelangen kann, wenn man einen 3-Keto-cholansäure- methylester,
der im Ring C in 12-Stellung einen zusammen mit einem benachbarten Wasserstoffatom abspaltbaren Substituenten aufweist, mit diesen Substituenten unter Bil dung einer Doppelbindung abspaltenden Mit teln behandelt.
Der 12-ständige, zusammen mit einem benachbarten Wasserstoffatom abspaltbare Substituent des Ausgangsstoffes kann eine freie" Hydroxylgruppe oder eine beispiels weise durch eine Carbonsäure, wie Essig-, Propion- oder Benzoesäure, durch eine Sulfonsäure, Halogenwasserstoffsäure oder Xanthogensäure veresterte Hydroxylgruppe sein.
Die Abspaltung dieses Substituenten unter Bildung einer Doppelbindung kann mit. den für diese Reaktion an sich bekannten Mitteln erfolgen. Beispielsweise lässt sich eine freie Hydroxylgruppe unter der Einwirkung von Mineralsäuren, vorzugsweise in Lösungs mitteln, wie Eisessig, Alkohol, Dioxan und dergl., von Phosphoroxychlorid, Bisulfaten, von Ameisensäure, Oxalsäure, von Säure anhydriden,
wie Acetanhydrid oder Phos- phorpentoxyd, oder durch die Einwirkung von Katalysatoren, wie Jod- oder Carbon- säuresalzen, abspalten. Eine veresterte Hy- droxylgruppe wird ausser durch die genann- ten Mittel vorzugsweise auch mit Alkalien, Erdalkalien, Carbonaten, organischen Basen, wie Pyridin, Dimethylanilin usw., abgespal ten.
An Stelle oder in Kombination mit den genannten Mitteln lässt sich auch erhöhte Temperatur und/oder verminderter Druck anwenden. Gegebenenfalls arbeitet man auch in Gegenwart indifferenter Gase. Statt aus Halogenwasserstoffsäureestern direkt Ha logenwasserstoff abzuspalten, kann man das Halogen auch in bekannter Weise durch einen quaternären Ammoniumrest ersetzen und diesen abspalten.
Das neue Verfahrensprodukt, der d11.12- 3-Keto-cholensäure-methylester vom F. 121 bis 123 , soll als Zwischenprodukt zur Her stellung therapeutisch wertvoller Produkte dienen.
<I>Beispiel:</I> 3-Keto-12-benzoyloxy-cholansäure-methyl- ester (erhalten aus 3-Oxy-12-acetoxy-cholan- säure-methylester durch Oxydation mit Chrom säure in Eisessig bei Zimmertemperatur, energische Verseifung mit Alkali, Behand lung mit methylalkoholischer Salzsäure und Benzoylierung) werden im. Wasserstrahl vakuum (12 mm) unter gleichzeitigem Ein leiten von Kohlendioxyd auf 320 Metallbad temperatur erhitzt.
Die abgespaltene Benzoe- säure destilliert langsam ab, worauf etwas abgekühlt und nach Einschalten von Hoch vakuum der ganze Kolbenrückstand über- destilliert wird. Man löst das glasige Destil- lat in Äther, wäscht die Ätherlösung mit Sodalösung und Wasser, trocknet und engt sie auf ein kleines Volumen ein.
Man ver setzt bis zur beginnenden Trübung mit Petroläther und erhält beim Stehen den ,d",12-3-geto-cholensäure-methylester der For mel
EMI0002.0007
Nach Umkristallisieren aus Methanol schmilzt er bei 121-123 .
Zu demselben Produkt gelangt man auch z. B. durch Erhitzen des 3-Keto-12-tosyloxy- oder 3-geto-12-mesyloxy-cholansäure-methyl- esters mit Pyridin oder Collidin.
Process for the production of a new compound of the cyclopentano polyhydrophenanthren series. It has been found that a compound of the cyclopentanopolyhydrophenanthrene series which is unsaturated in the ring C can be obtained if a methyl 3-keto-cholanoate,
which has a substituent which can be split off together with an adjacent hydrogen atom in the 12-position in ring C, treated with these substituents to form a double bond.
The 12-position substituent of the starting material which can be split off together with an adjacent hydrogen atom can be a free "hydroxyl group or a hydroxyl group esterified, for example, by a carboxylic acid such as acetic, propionic or benzoic acid, by a sulfonic acid, hydrohalic acid or xanthic acid.
The elimination of this substituent with the formation of a double bond can with. the means known per se for this reaction. For example, a free hydroxyl group can be anhydrides under the action of mineral acids, preferably in solvents, such as glacial acetic acid, alcohol, dioxane and the like, of phosphorus oxychloride, bisulfates, of formic acid, oxalic acid, of acid,
such as acetic anhydride or phosphorus pentoxide, or through the action of catalysts such as iodine or carboxylic acid salts. In addition to the agents mentioned, an esterified hydroxyl group is preferably also split off with alkalis, alkaline earths, carbonates, organic bases such as pyridine, dimethylaniline, etc.
Instead of or in combination with the agents mentioned, it is also possible to use increased temperature and / or reduced pressure. You may also work in the presence of inert gases. Instead of splitting off hydrogen halide directly from hydrohalic acid esters, the halogen can also be replaced in a known manner by a quaternary ammonium radical and split off.
The new process product, the d11.12- 3-keto-cholenic acid methyl ester from F. 121 to 123, is intended to serve as an intermediate for the manufacture of therapeutically valuable products.
<I> Example: </I> 3-Keto-12-benzoyloxy-cholanic acid methyl ester (obtained from 3-oxy-12-acetoxy-cholanic acid methyl ester by oxidation with chromic acid in glacial acetic acid at room temperature, vigorous saponification with alkali, treatment with methyl alcoholic hydrochloric acid and benzoylation) are im. Water jet vacuum (12 mm) heated to 320 metal bath temperature with simultaneous introduction of carbon dioxide.
The split-off benzoic acid slowly distills off, whereupon it is cooled somewhat and, after switching on the high vacuum, the entire flask residue is distilled over. The glassy distillate is dissolved in ether, the ethereal solution is washed with soda solution and water, dried and concentrated to a small volume.
One sets ver with petroleum ether until the onset of cloudiness and, on standing, receives the "d", 12-3-geto-cholenic acid methyl ester of the formula
EMI0002.0007
After recrystallization from methanol, it melts at 121-123.
The same product can also be obtained e.g. B. by heating the 3-keto-12-tosyloxy or 3-geto-12-mesyloxy-cholanic acid methyl ester with pyridine or collidine.
Claims (1)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH246178T | 1942-01-28 | ||
| CH240789T | 1942-01-28 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH246178A true CH246178A (en) | 1946-12-15 |
Family
ID=25728542
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH246178D CH246178A (en) | 1942-01-28 | 1942-01-28 | Process for the preparation of a new compound of the cyclopentano-polyhydrophenanthrene series. |
Country Status (1)
| Country | Link |
|---|---|
| CH (1) | CH246178A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5741512A (en) * | 1988-09-16 | 1998-04-21 | Novartis Corporation | Pharmaceutical compositions comprising cyclosporins |
| US5759997A (en) | 1984-07-24 | 1998-06-02 | Novartis Ag | Cyclosporin galenic forms |
-
1942
- 1942-01-28 CH CH246178D patent/CH246178A/en unknown
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5759997A (en) | 1984-07-24 | 1998-06-02 | Novartis Ag | Cyclosporin galenic forms |
| US5977066A (en) | 1984-07-24 | 1999-11-02 | Novartis Ag | Cyclosporin galenic forms |
| US5741512A (en) * | 1988-09-16 | 1998-04-21 | Novartis Corporation | Pharmaceutical compositions comprising cyclosporins |
| US5916589A (en) | 1988-09-16 | 1999-06-29 | Novartis Ag | Pharmaceutical compositions comprising cyclosporins |
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