CH414620A - Process for the preparation of 20,20-bis (nitratomethylene) -5B-pregnanes - Google Patents
Process for the preparation of 20,20-bis (nitratomethylene) -5B-pregnanesInfo
- Publication number
- CH414620A CH414620A CH4846661A CH4846661A CH414620A CH 414620 A CH414620 A CH 414620A CH 4846661 A CH4846661 A CH 4846661A CH 4846661 A CH4846661 A CH 4846661A CH 414620 A CH414620 A CH 414620A
- Authority
- CH
- Switzerland
- Prior art keywords
- nitratomethylene
- bis
- preparation
- pregnanes
- sep
- Prior art date
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J51/00—Normal steroids with unmodified cyclopenta(a)hydrophenanthrene skeleton not provided for in groups C07J1/00 - C07J43/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J17/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, having an oxygen-containing hetero ring not condensed with the cyclopenta(a)hydrophenanthrene skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J41/00—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring
- C07J41/0033—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005
- C07J41/0055—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005 the 17-beta position being substituted by an uninterrupted chain of at least three carbon atoms which may or may not be branched, e.g. cholane or cholestane derivatives, optionally cyclised, e.g. 17-beta-phenyl or 17-beta-furyl derivatives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J75/00—Processes for the preparation of steroids in general
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Steroid Compounds (AREA)
Description
Verfahren zur Herstellung von 20,20-Bis-(nitratomethylen)-5ss-pregnanen Die Erfindung betrifft ein Verfahren zur Her stellung von Steroiden der allgemeinen Formel
EMI0001.0003
in der R ein Wasserstoffatom oder einen Säurerest, wie z. B. die Gruppen -Acyl, N02 oder -SO3M, wobei M ein Alkalimetall ist, bedeutet.
Das erfindungsgemässe Verfahren besteht darin, dass man eine Verbindung der Formel
EMI0001.0007
worin R ein Wasserstoffatom oder einen Säurerest bedeutet, zwecks Überführung der in 11-Stellung vorhandenen Ketofunktion in eine Alkoholgruppe der Einwirkung eines Mischhydrids unterwirft. Die Reduktion der 11-Ketogruppe erfolgt vor zugsweise mit Kalium-, Natrium- oder Lithiumbor- hydrid oder Lithiumaluminiumhydrid, wobei man vorteilhafterweise in Tetrahydrofuran arbeitet.
Die Verbindung der Formel I zeigen starke blut gefässerweiternde Wirkung auf die Coronargefässe, bestimmt nach dem Verfahren von Langendorff am isolierten Kaninchenherzen.
Die Wirksamkeit der erfindungsgemäss hergestell ten Verbindung dauert länger an und ist stärker als die von Trinitroglycerin.
Das folgende Beispiel erläutert das erfindungs gemässe Verfahren. <I>Beispiel</I> 3aα11ss-Dihydroxy-20,20-bis-(nitratomethylen)- 5ss-pregnan der Formel I (R=H) Man versetzt 12,5 cm3 Tetrahydrofuran bei 18 bis 20 C mit 139 mg Lithiumaluminiumhydrid und versetzt dann bei der gleichen Temperatur in etwa 10 Minuten mit einer Lösung von 500 mg 3aαHy- droxy-11-keto- 20,20-bis-(nitratomethylen)-5ss-pre- gnan in. 25 cm3 Tetrahydrofuran.
Man lässt die Re aktionsmischung dann während etwa 4 Stunden unter Rühren und unter Stickstoff bei Zimmertemperatur stehen.
Anschliessend: gibt man 10 cm3 Essigsäureäthyl- ester hinzu, rührt während etwa 10 Minuten und versetzt mit 5 cm3 18 %iger Natriumchloridlösung, dekantiert die Lösung, trocknet über Natriumsulfat, filtriert und engt zur Trockne ein.
Das Rohprodukt wird durch Chromatographieren an aktiviertem Magnesiumsilikat, Eluieren mit Methylenchlorid, das 2% Tetrachlorkohlenstoff ent- hält, und anschliessendes Umkristallisieren aus Iso- propyläther gereinigt. Man erhält 207 mg 3aα11,ss- Dihydroxy-20,20-bis -- (nitratomethylen)-5ss-pregnan der Formel I (R=H vom F = 135 C und [aα20 = + 20,4 (c = 1 % in Dioxan).
Die Verbindung ist löslich in Alkohol, Äther, Aceton, Benzol, Chloroform und Isopropyläther und unlöslich in Wasser und verdünnten wässrigen Säuren und Alkalien.
Ananlyse: C23H38O8N2, Molekulargewicht = 470,55,
EMI0002.0005
berechnet: <SEP> C <SEP> 58,70 <SEP> H <SEP> 8,14 <SEP> %,
<tb> gefunden: <SEP> 58,9 <SEP> 8,0 <SEP> %. Die Verbindung wurde bisher nicht beschrieben.
Process for the preparation of 20,20-bis- (nitratomethylene) -5ss-pregnanes The invention relates to a process for the preparation of steroids of the general formula
EMI0001.0003
in which R is a hydrogen atom or an acid radical, such as. B. the groups -acyl, NO2 or -SO3M, where M is an alkali metal, means.
The inventive method consists in that one compound of the formula
EMI0001.0007
where R denotes a hydrogen atom or an acid residue, is subjected to the action of a mixed hydride in order to convert the keto function present in the 11-position into an alcohol group. The 11-keto group is preferably reduced with potassium, sodium or lithium borohydride or lithium aluminum hydride, which is advantageously carried out in tetrahydrofuran.
The compounds of formula I show a strong vasodilator effect on the coronary vessels, determined by the Langendorff method on isolated rabbit hearts.
The effectiveness of the compound produced according to the invention lasts longer and is stronger than that of trinitroglycerin.
The following example explains the method according to the invention. <I> Example </I> 3aα11ss-dihydroxy-20,20-bis- (nitratomethylene) -5ss-pregnane of the formula I (R = H) 139 mg are added to 12.5 cm3 of tetrahydrofuran at 18-20 ° C Lithium aluminum hydride and then added a solution of 500 mg 3aα-hydroxy-11-keto-20,20-bis- (nitratomethylene) -5ss-pregnan in 25 cm3 tetrahydrofuran at the same temperature in about 10 minutes.
The reaction mixture is then left to stand for about 4 hours with stirring and under nitrogen at room temperature.
Then: add 10 cm3 of ethyl acetate, stir for about 10 minutes and add 5 cm3 of 18% sodium chloride solution, decant the solution, dry over sodium sulphate, filter and concentrate to dryness.
The crude product is purified by chromatography on activated magnesium silicate, eluting with methylene chloride containing 2% carbon tetrachloride, and subsequent recrystallization from isopropyl ether. 207 mg of 3aα11, s-dihydroxy-20,20-bis - (nitratomethylene) -5ss-pregnan of the formula I (R = H from F = 135 C and [a α 20 = + 20.4 (c = 1% in dioxane).
The compound is soluble in alcohol, ether, acetone, benzene, chloroform and isopropyl ether and insoluble in water and dilute aqueous acids and alkalis.
Analysis: C23H38O8N2, molecular weight = 470.55,
EMI0002.0005
calculated: <SEP> C <SEP> 58.70 <SEP> H <SEP> 8.14 <SEP>%,
<tb> found: <SEP> 58.9 <SEP> 8.0 <SEP>%. The connection has not yet been described.
Claims (1)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR819007A FR1363108A (en) | 1960-02-19 | 1960-02-19 | Bis-hydroxymethylene pregnane derivative and method of preparation |
| FR830528A FR83204E (en) | 1960-06-20 | 1960-06-20 | Bis-hydroxymethylene pregnane derivatives and method of preparation |
| FR830781A FR83551E (en) | 1960-06-22 | 1960-06-22 | Bis-hydroxymethylene pregnane derivatives and method of preparation |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH414620A true CH414620A (en) | 1966-06-15 |
Family
ID=27245407
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH4846661A CH414620A (en) | 1960-02-19 | 1961-02-17 | Process for the preparation of 20,20-bis (nitratomethylene) -5B-pregnanes |
| CH194761A CH431513A (en) | 1960-02-19 | 1961-02-17 | Process for the preparation of 20,20-bis (nitratomethylene) -5B-pregnanes |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH194761A CH431513A (en) | 1960-02-19 | 1961-02-17 | Process for the preparation of 20,20-bis (nitratomethylene) -5B-pregnanes |
Country Status (3)
| Country | Link |
|---|---|
| CH (2) | CH414620A (en) |
| ES (1) | ES264431A1 (en) |
| SE (1) | SE304263B (en) |
-
1961
- 1961-01-28 ES ES264431A patent/ES264431A1/en not_active Expired
- 1961-02-17 CH CH4846661A patent/CH414620A/en unknown
- 1961-02-17 CH CH194761A patent/CH431513A/en unknown
-
1965
- 1965-01-20 SE SE758/65A patent/SE304263B/xx unknown
Also Published As
| Publication number | Publication date |
|---|---|
| CH431513A (en) | 1967-03-15 |
| ES264431A1 (en) | 1961-06-16 |
| SE304263B (en) | 1968-09-23 |
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