CH240789A - Process for the preparation of a new compound of the cyclopentanopolyhydrophenanthrene series. - Google Patents

Process for the preparation of a new compound of the cyclopentanopolyhydrophenanthrene series.

Info

Publication number
CH240789A
CH240789A CH240789DA CH240789A CH 240789 A CH240789 A CH 240789A CH 240789D A CH240789D A CH 240789DA CH 240789 A CH240789 A CH 240789A
Authority
CH
Switzerland
Prior art keywords
preparation
dione
new compound
ring
compound
Prior art date
Application number
Other languages
German (de)
Inventor
Reichstein Tadeus Dr Professor
Original Assignee
Reichstein Tadeus Dr Professor
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
Application filed by Reichstein Tadeus Dr Professor filed Critical Reichstein Tadeus Dr Professor
Publication of CH240789A publication Critical patent/CH240789A/en

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

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Steroid Compounds (AREA)

Description

  

  Verfahren zur Herstellung einer neuen Verbindung der     Cyelopentanopolyhydro-          phenanthr        en-Reihe.       Es     wurde        gefunden,    dass man zu einer im  Ring C     ungesättigten    Verbindung der     Cyclo-          pentanopolyhydrophenanthren-Reihe    gelangen  kann, Wenn man ein d     4,5-Pregnen-8,20-dion,     das im Ring C in     12-Stellung    einen zusam  men mit einem benachbarten Wasserstoff  atom     abspaltbaren        Substituenten    aufweist,

    mit diesen     Substituenten    unter Bildung     einer     Doppelbindung abspaltenden Mitteln behan  delt.  



  Der     12ständige    zusammen mit     einem        be-          naehbarten    Wasserstoffatom     abspaltbare        Sub-          stituent    des Ausgangsstoffes kann eine freie       Hydroxylgruppe    oder eine beispielsweise  durch     Karbonsäuren,    wie Essig-,     Propion-          oder        Benzoesäure,    durch     Sulfonsäuren,    Halo  genwasserstoffsäuren oder     Xanthogensäuren     veresterte     Hydrogylgruppe    sein.  



  Die Abspaltung dieses     Substituenten     unter Bildung     einer    Doppelverbindung kann  mit den für diese Reaktion an sich bekannten  Mitteln erfolgen. Beispielsweise lässt sich eine  freie     Hydroxylgruppe    unter der Einwirkung    von Mineralsäuren, vorzugsweise in     Iaösungs-          mitteln,    wie Eisessig, Alkohol,     Dioxan    und  dergleichen, von     Phosphoroxychlorid,        Bisul-          faten,    von Ameisensäure,     Ogalsäure,    von       Säureanhydriden,

      wie     Acetanhydrid    oder       Phosphorpentoxyd,    oder durch die Einwir  kung von Katalysatoren, wie Jod- oder     Kar-          bonsäuresaIzen    abspalten. Eine veresterte       Hydrogylgruppe    wird ausser durch die ge  nannten Mittel vorzugsweise auch mit     Alka-          lien,    Erdalkalien,     Karbonaten,        karbonsauren     Salzen, organischen Basen, wie     Pyridin,        Di-          methylanilin    usw., abgespalten.

   An Stelle  oder     in        Kombination    mit den     genannten     Mitteln lässt sich auch erhöhte     Temperatur          undloder        verminderter    Druck anwenden.  Gegebenenfalls arbeitet man auch in Gegen  wart indifferenter Gase.

   Statt aus Halogen  wasserstoffsäureester direkt Halogenwasser  stoff abzuspalten, kann man das Halogen  auch in bekannter Weise durch     einen        quater-          nären        Ammoniumrest    ersetzen und diesen ab  spalten. ,-      Das neue Verfahrensprodukt, das     d4>5;11,12-          Pregnadien-3,20-dion,    schmilzt bei 175-l77 .

    Es soll therapeutische Verwendung finden  oder als     Zwischenprodukt    zur Herstellung       therapeutisch    wertvoller Produkte     dienen.            Beispiel:     1 Teil     d4.5-12-Acetoxy-pregnen-3,20-dion          (12-Acetoxy-progesteron,        F.183 )    oder     d4.5-          12-Benzoxy-pregnen-3,20-dion        (12-Benzoxy-          progesteron,    F.164 ) wird unter Stickstoff  oder im Vakuum bei 12 mm 1-2     Stunden        auf          300-340     erwärmt.

   Nachdem das     Schäumen     nachgelassen hat,     wird    im Hochvakuum über  destilliert und das     Destillat    in Äther auf  genommen. Die Ätherlösung wird sodann  neutral gewaschen, getrocknet     und    einge  dampft. Der Rückstand gibt nach - dem       Chromatographieren    über eine Säule von  15 Teilen     Aluminiumoxyd    eine     Verbindung     vom F. 175-l77 , der die Konstitution eines       d4,5;        11,12-Pregnadien-3,20-dions    mit der For  mel  
EMI0002.0026     
    zukommt.

    An Stelle     eines        12-Acyloxy-progesterons     lässt sich zum Beispiel auch die     unsubstituierte     oder die mit einer     Halogenwasserstoffsäure     veresterte     12-Oxy-Verbindung    verwenden.  Im letzteren Falle setzt man das     Halogenid     vorteilhaft mit     Pyridin    um und spaltet das         entstehende        Pyridiniumsalz    thermisch.

   Zur       Abspaltung    der veresterten und insbesondere  der freien     Hydroxylgruppe    können auch saure       Mittel    verwendet werden, zum Beispiel eine  Mischung von Eisessig und     konzentrierter     Salzsäure. Ferner ist es zweckmässig,     Xantho-          gensäureester    ebenfalls einer thermischen       Spaltung    zu unterwerfen.



  Process for the preparation of a new compound of the Cyelopentanopolyhydphenanthr en series. It has been found that a compound of the cyclopentanopolyhydrophenanthrene series which is unsaturated in ring C can be obtained if one ad 4,5-pregnene-8,20-dione that is in the 12-position in ring C together with a neighboring hydrogen atom has removable substituents,

    treated with these substituents to form a double bond cleaving agents.



  The substituent of the starting material that can be split off together with an adjacent hydrogen atom can be a free hydroxyl group or a hydroyl group esterified, for example, by carboxylic acids such as acetic, propionic or benzoic acid, by sulfonic acids, hydrohalic acids or xanthogenic acids.



  This substituent can be split off with the formation of a double compound using the means known per se for this reaction. For example, a free hydroxyl group can be removed 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, ogalic acid, of acid anhydrides,

      such as acetic anhydride or phosphorus pentoxide, or by the action of catalysts such as iodine or carbonic acid salts. In addition to the agents mentioned, an esterified hydroyl group is preferably also split off with alkalies, alkaline earths, carbonates, carbonic acid salts, organic bases such as pyridine, dimethylaniline, etc.

   Instead of or in combination with the agents mentioned, increased temperature and / or reduced pressure can also be used. If necessary, one also works in the presence of indifferent gases.

   Instead of splitting off hydrogen halide directly from hydrogen halide, the halogen can also be replaced in a known manner by a quaternary ammonium radical and this can be split off. - The new process product, d4> 5; 11,12-pregnadiene-3,20-dione, melts at 175-177.

    It should find therapeutic use or serve as an intermediate for the manufacture of therapeutically valuable products. Example: 1 part d4.5-12-acetoxy-pregnen-3,20-dione (12-acetoxy-progesterone, F.183) or d4.5-12-benzoxy-pregnen-3,20-dione (12-benzoxy - progesterone, F.164) is heated to 300-340 for 1-2 hours under nitrogen or in a vacuum at 12 mm.

   After the foaming has subsided, it is distilled in a high vacuum and the distillate is taken up in ether. The ether solution is then washed neutral, dried and evaporated. After chromatography on a column of 15 parts of aluminum oxide, the residue gives a compound of F. 175-177 which has the constitution of a d4.5; 11,12-Pregnadien-3,20-dions with the formula
EMI0002.0026
    comes to.

    Instead of a 12-acyloxy-progesterone, it is also possible, for example, to use the unsubstituted or the 12-oxy compound esterified with a hydrohalic acid. In the latter case, the halide is advantageously reacted with pyridine and the resulting pyridinium salt is thermally cleaved.

   Acidic agents can also be used to split off the esterified and, in particular, the free hydroxyl group, for example a mixture of glacial acetic acid and concentrated hydrochloric acid. Furthermore, it is expedient to subject xanthogen acid esters to thermal cleavage as well.

Claims (1)

PATENTANSPRUCH: Verfahren zur Herstellung einer im Ring C ungesättigten Verbindung der Cyclopentano- polyhydrophenanthren-Reihe, dadurch ge kennzeichnet, dass man ein 44,5-Pregnen-3,20- dion, das im Ring C in 12-Stellung einen zu sammen mit einem benachbarten Wasserstoff atom abspaltbaren Substituenten. aufweist, mit diesen Substituenten unter Bildung einer Doppelbindung abspaltenden Mitteln behan delt. PATENT CLAIM: A process for the preparation of a compound of the cyclopentano-polyhydrophenanthrene series which is unsaturated in the ring C, characterized in that a 44,5-pregnene-3,20-dione, which is in the 12-position in the ring C together with a neighboring hydrogen atom-removable substituents. has, treated with these substituents to form a double bond cleaving agents. Das neue Verfahrensprodukt, das d4,5# 11,12-Pregnadien-3,20-dion, schmilzt bei 175 bis 177 . Es soll therapeutische Verwendung finden oder als Zwischenprodukt zur Herstel lung therapeutisch wertvoller Produkte die nen. UNTERANSPRüCHE 1. Verfahren nach Patentanspruch, da durch gekennzeichnet, dass man als Ausgangs stoff ein 12-Acyloxy-progesteron verwendet. 2. The new process product, d4,5 # 11,12-pregnadiene-3,20-dione, melts at 175 to 177. It is intended to be used therapeutically or as an intermediate in the manufacture of therapeutically valuable products. SUB-CLAIMS 1. A method according to claim, characterized in that a 12-acyloxy-progesterone is used as the starting material. 2. Verfahren nach Patentanspruch und Unteranspruch 1, dadurch gekennzeichnet, dass man den Ausgangsstoff einer thermischen Zersetzung unterwirft. Process according to claim and dependent claim 1, characterized in that the starting material is subjected to thermal decomposition.
CH240789D 1942-01-28 1941-03-21 Process for the preparation of a new compound of the cyclopentanopolyhydrophenanthrene series. CH240789A (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CH240789T 1942-01-28

Publications (1)

Publication Number Publication Date
CH240789A true CH240789A (en) 1946-01-31

Family

ID=4461964

Family Applications (1)

Application Number Title Priority Date Filing Date
CH240789D CH240789A (en) 1942-01-28 1941-03-21 Process for the preparation of a new compound of the cyclopentanopolyhydrophenanthrene series.

Country Status (1)

Country Link
CH (1) CH240789A (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6475519B1 (en) 1997-01-30 2002-11-05 Novartis Ag Oil-free pharmaceutical compositions containing cyclosporin A

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6475519B1 (en) 1997-01-30 2002-11-05 Novartis Ag Oil-free pharmaceutical compositions containing cyclosporin A
US6723339B2 (en) 1997-01-30 2004-04-20 Novartis Ag Oil-free pharmaceutical compositions containing cyclosporin A

Similar Documents

Publication Publication Date Title
CH240789A (en) Process for the preparation of a new compound of the cyclopentanopolyhydrophenanthrene series.
EP0087576B1 (en) Process for preparing tocopheryl acetate or tocopheryl propionate
CH246178A (en) Process for the preparation of a new compound of the cyclopentano-polyhydrophenanthrene series.
CH245269A (en) Process for the preparation of a new compound of the cyclopentanopolyhydrophenanthrene series.
CH242991A (en) Process for the preparation of a new compound of the cyclopentanopolyhydro-phenanthrene series.
CH245274A (en) Process for the preparation of a new compound of the cyclopentanopolyhydrophenanthrene series.
CH242992A (en) Process for the preparation of a new compound of the cyclopentanopolyhydro-phenanthrene series.
AT163742B (en) Process for the preparation of esters of pyridyl-3-carbinol
CH242993A (en) Process for the preparation of a new compound of the cyclopentanopolyhydro-phenanthrene series.
CH246179A (en) Process for the preparation of a new compound of the cyclopentano-polyhydrophenanthrene series.
CH245275A (en) Process for the preparation of a new compound of the cyclopentanopolyhydrophenanthrene series.
CH246177A (en) Process for the preparation of a new compound of the cyclopentano-polyhydrophenanthrene series.
DE934590C (en) Process for the preparation of alkylsulfonylbenzaldehydes
DE1518246C (en) Process for the production of sucrose esters of substituted stearic acids
DE870408C (en) Process for the preparation of 17-monoesters of androstane-3-cis-17-trans-diol
AT160572B (en) Process for the preparation of unsaturated oxyketones of the cyclopentanopolydrophenanthrene series or their derivatives.
AT368521B (en) METHOD FOR PRODUCING NEW 2.9 ALPHA
DE892451C (en) Process for the preparation of A7-androstene-3, 17-diols and their O-derivatives, preferably their esters
DE842053C (en) Process for the production of derivatives of the cyclopentanopoly-hydropenanthrene or the polyhydrochrysenic series
AT239970B (en) Process for the preparation of Δ <16> -20-ketopregnene derivatives
AT228945B (en) Process for the production of new modification products of the 17α-hydroxyprogesterone ester
AT164549B (en) Process for the production of sterol degradation products
DE928528C (en) Process for the production of nicotinic acid esters
CH245273A (en) Process for the preparation of a new compound of the cyclopentanopolyhydrophenanthrene series.
CH245270A (en) Process for the preparation of a new compound of the cyclopentanopolyhydrophenanthrene series.