CH414620A - Process for the preparation of 20,20-bis (nitratomethylene) -5B-pregnanes - Google Patents

Process for the preparation of 20,20-bis (nitratomethylene) -5B-pregnanes

Info

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
Application number
CH4846661A
Other languages
German (de)
Inventor
Bertin Daniel
Fritel Hubert
Muller Georges
Mathieu Jean
Original Assignee
Roussel Uclaf
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from FR819007A external-priority patent/FR1363108A/en
Priority claimed from FR830528A external-priority patent/FR83204E/en
Priority claimed from FR830781A external-priority patent/FR83551E/en
Application filed by Roussel Uclaf filed Critical Roussel Uclaf
Publication of CH414620A publication Critical patent/CH414620A/en

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>       3a&alpha;11ss-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     3a&alpha;Hy-          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     3a&alpha;11,ss-          Dihydroxy-20,20-bis    -- (nitratomethylen)-5ss-pregnan  der Formel I (R=H vom F = 135 C und [a&alpha;20 =  + 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)

PATENTANSPRUCH Verfahren zur Herstellung von Verbindungen der allgemeinen Formel I EMI0002.0008 in der R ein Wasserstoffatom oder einen Säurerest bedeutet, dadurch gekennzeichnet, dass man eine Ver bindung der Formel EMI0002.0009 zwecks Überführung der in 11-Stellung vorhandenen Ketofunktion in eine Alkoholgruppe der Einwirkung eines Mischhydrids unterwirft. UNTERANSPRÜCHE 1. Verfahren nach Patentanspruch, dadurch ge kennzeichnet, dass man als Mischhydrid Kalium-, Natrium- oder Lithiumborhydrid oder Lithiumalu- miniumhydrid verwendet. 2. Verfahren nach Patentanspruch und Unter anspruch 1, dadurch gekennzeichnet, dass man die Hydrierung in Tetrahydrofuran durchführt. PATENT CLAIM Process for the preparation of compounds of general formula I. EMI0002.0008 in which R denotes a hydrogen atom or an acid residue, characterized in that one is a compound of the formula EMI0002.0009 subjected to the action of a mixed hydride for the purpose of converting the keto function present in the 11-position into an alcohol group. SUBClaims 1. Method according to patent claim, characterized in that potassium, sodium or lithium borohydride or lithium aluminum hydride is used as the mixed hydride. 2. The method according to claim and sub-claim 1, characterized in that the hydrogenation is carried out in tetrahydrofuran.
CH4846661A 1960-02-19 1961-02-17 Process for the preparation of 20,20-bis (nitratomethylene) -5B-pregnanes CH414620A (en)

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
CH194761A CH431513A (en) 1960-02-19 1961-02-17 Process for the preparation of 20,20-bis (nitratomethylene) -5B-pregnanes
CH4846661A CH414620A (en) 1960-02-19 1961-02-17 Process for the preparation of 20,20-bis (nitratomethylene) -5B-pregnanes

Family Applications Before (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) CH431513A (en)
ES (1) ES264431A1 (en)
SE (1) SE304263B (en)

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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