CH507923A - 19-alkyl steroids - Google Patents

19-alkyl steroids

Info

Publication number
CH507923A
CH507923A CH1782470A CH1782470A CH507923A CH 507923 A CH507923 A CH 507923A CH 1782470 A CH1782470 A CH 1782470A CH 1782470 A CH1782470 A CH 1782470A CH 507923 A CH507923 A CH 507923A
Authority
CH
Switzerland
Prior art keywords
alkyl
sep
delta4
steroids
delta3
Prior art date
Application number
CH1782470A
Other languages
German (de)
Inventor
Andor Dr Fuerst
Gerhard Dr Herzog Ernst
Marcel Dr Mueller
Peter Dr Mueller
Original Assignee
Hoffmann La Roche
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 Hoffmann La Roche filed Critical Hoffmann La Roche
Priority to CH1782470A priority Critical patent/CH507923A/en
Publication of CH507923A publication Critical patent/CH507923A/en

Links

Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07JSTEROIDS
    • C07J1/00Normal steroids containing carbon, hydrogen, halogen or oxygen, not substituted in position 17 beta by a carbon atom, e.g. estrane, androstane
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07JSTEROIDS
    • C07J75/00Processes 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)

Abstract

19-Alkyl steroids of general formula (I) where R' = H or C1-6-alkyl; R" = HO, AcylO or C1-6-alkoxy; R3 = H, C1-6-alkyl or R4 which = C2-6-alkenyl or alkynyl. R(when R' = alkyl and R3 = H or 1-6 C alkyl) = 3-keto-DELTA4,6 or -DELTA1,4,6; 3-acyloxy-DELTA3,5 or -DELTA2,4,6; 3-alkoxy-DELTA3,5 or -DELTA3,5,7; 3-OH (or OAlk or OAcyl)-DELTA4 or -DELTA4,6; And, when R' = H and R3 = R4, R = 3-keto-DELTA4 or -DELTA1,4; Preferred are R3 = R4; R = 3-OH(or Oalk or OAcyl)-DELTA4 or -DELTA4,6. Hormonally active compds. They affect the body gonadotrophin and hinder the action of progesterone. Used for fertility control.

Description

  

  
 



  Verfahren zur Herstellung von 19-Alkylsteroiden
Die Erfindung betrifft ein Verfahren zur Herstellung von   1 9-Alkylsteroiden    der Formeln
EMI1.1     


<tb>  <SEP> R <SEP> 1
<tb>  <SEP> t <SEP> R)
<tb>  <SEP> 
<tb> Xcyl-O <SEP> 4 <SEP> bzw.
<tb>



   <SEP> Ia
<tb>  <SEP> ru <SEP> kl
<tb>  <SEP> In
<tb>  <SEP> Ib
<tb>  <SEP> Aey1-O <SEP> 
<tb>  worin R1 Wasserstoff oder   Cl -Alkyl,    R2 Hydroxy, Acyloxy oder   C1 6-Alkoxy    und R3 Wasserstoff,   C1 6-Alkyl    oder   C2 6-Alkinyl    darstellen.



   Eine bevorzugte Gruppe von erfindungsgemäss erhältlichen Verbindungen ist diejenige, in der R3 einen Alkinylrest darstellt.



   Das erfindungsgemässe Verfahren ist dadurch gekennzeichnet, dass man eine Verbindung der Formel
EMI1.2     
 worin R1,   R2    und R3 die oben angegebenen Bedeutungen haben, oder ein   A6-Dehydroderivat    davon enolverestert.



   Die vorstehend verwendeten Bezeichnungen   C16-AI-    kyl und   C2 6-Alkinyl    beziehen sich auf solche Kohlen wasserstoffreste, die 1-6 bzw. 2-6 C-Atome enthalten und die geradkettig oder verzweigt sein können. Bei spiele für   Cl s-Alkyl    sind Methyl, Äthyl, Propyl, Isopro pyl, Butyl, Isobutyl, tert.Butyl, Pentyl und Hexyl. Bei spiele für   C2r-Alkinylreste    sind   Äthinyl,    Propinyl und
Propargyl.



   Eine durch das Symbol R2 dargestellte Acyloxygrup pe sowie eine 3-Acyloxygruppe enthalten vorzugsweise den Acylrest einer gesättigten oder ungesättigten, alipha tischen oder aromatischen Carbonsäure mit 1-10 Kohlen stoffatomen. Beispiele solcher Säuren sind Essigsäure,
Propionsäure, Capronsäure, Pivalinsäure, Buttersäure, Isobuttersäure und Benzoesäure. Beispiele für eine   C-1 6-    Alkoxygruppe sind Methoxy, Äthoxy und tert.Butoxy.



   Die erfindungsgemässe Enolveresterung einer Verbindung der Formel II oder eines A6-Dehydroderivates davon wird nach an sich bekannten Methoden durchgeführt, d.h. durch Behandlung mit einem Acylierungsmittel, wie zum Beispiel Isopropenylacetat, in Gegenwart eines Katalysators, wie p-Toluolsulfosäure, wobei 3   -Acyloxy-A3 5-    bzw.   3-Acyloxy-2,4,6-steroide    der Formel I erhalten werden.  



   Die 19-Alkylsteroide der Formel Ia bzw. lb sind hormonal wirksam. Sie beeinflussen den Gonadotropinhaushalt des Körpers und hemmen die Wirkung von Progesteron. Sie können als Mittel zur Fertilitätskontrolle Verwendung finden, z.B. in Form pharmazeutischer Präparate, welche sie in Mischung mit einem für die enterale oder parenterale Applikation geeigneten pharmazeutischen, organischen oder anorganischen inerten Trägermaterial enthalten. Die pharmazeutischen Präparate können in fester Form oder in flüssiger Form vorliegen.



  Gegebenenfalls enthalten sie Hilfsstoffe, wie Konservierungs-, Stabilisierungs-, Netz- oder Emulgiermittel, Salze zur Veränderung des osmotischen Druckes oder Puffers.



  Sie können auch noch andere therapeutisch wertvolle Stoffe enthalten.



   Beispiel    600 mg 17 -Äthinyl-19-äthyl-17P -hydroxyandrost-4-    -en-3-on werden in 24 ml Acetanhydrid gelöst, mit 300 mg p-Toluolsulfonsäure versetzt und über Nacht bei Zimmertemperatur unter Argon gerührt. Man giesst das Reaktionsgemisch auf eiskalte Natriumbicarbonatlösung, rührt während einer Stunde, extrahiert mit Äther und wäscht die Extrakte 4mal mit gesättigter Bicarbonatlösung und 1mal mit Wasser. Nach Zugabe einiger Tropfen Pyridin trocknet man über Natriumsulfat und dampft das Lösungsmittel ab. Der Rückstand wird an der 50fachen Menge Silicagel mit Hexan/Aceton   5:1    chromatographiert. Man erhält   350 mg 17a-Äthinyl-19-äthyl-3,17-    -diacetoxy-androsta-3,5-dien, welches nach Kristallisation aus Aceton/Hexan bei 181 bis 1840 schmilzt. 

  UV:   E232    = 18650;   (z]2s9    2030 (c = 0,1 in Dioxan). 



  
 



  Process for the preparation of 19-alkyl steroids
The invention relates to a process for the preparation of 19-alkyl steroids of the formulas
EMI1.1


<tb> <SEP> R <SEP> 1
<tb> <SEP> t <SEP> R)
<tb> <SEP>
<tb> Xcyl-O <SEP> 4 <SEP> or
<tb>



   <SEP> Ia
<tb> <SEP> ru <SEP> kl
<tb> <SEP> In
<tb> <SEP> Ib
<tb> <SEP> Aey1-O <SEP>
<tb> where R1 is hydrogen or C1-alkyl, R2 is hydroxy, acyloxy or C1-6-alkoxy and R3 is hydrogen, C1-6-alkyl or C2-6-alkynyl.



   A preferred group of compounds obtainable according to the invention is that in which R3 represents an alkynyl radical.



   The inventive method is characterized in that a compound of the formula
EMI1.2
 in which R1, R2 and R3 have the meanings given above, or an A6-dehydro derivative thereof is enol-esterified.



   The terms C16-alkyl and C2 6-alkynyl used above refer to those hydrocarbon radicals which contain 1-6 or 2-6 carbon atoms and which can be straight-chain or branched. Examples of Cl s-alkyl are methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl and hexyl. Examples of C2r-alkynyl radicals are ethynyl, propynyl and
Propargyl.



   An acyloxy group represented by the symbol R2 and a 3-acyloxy group preferably contain the acyl radical of a saturated or unsaturated, aliphatic or aromatic carboxylic acid with 1-10 carbon atoms. Examples of such acids are acetic acid,
Propionic acid, caproic acid, pivalic acid, butyric acid, isobutyric acid and benzoic acid. Examples of a C-1-6 alkoxy group are methoxy, ethoxy and tert-butoxy.



   The enol esterification according to the invention of a compound of the formula II or an A6-dehydro derivative thereof is carried out according to methods known per se, i. by treatment with an acylating agent, such as, for example, isopropenyl acetate, in the presence of a catalyst, such as p-toluenesulfonic acid, 3-acyloxy-A3 5- or 3-acyloxy-2,4,6-steroids of the formula I being obtained.



   The 19-alkyl steroids of the formula Ia and Ib are hormonally active. They influence the body's gonadotropin balance and inhibit the effects of progesterone. They can be used as a means of fertility control, e.g. in the form of pharmaceutical preparations which they contain in a mixture with a pharmaceutical, organic or inorganic inert carrier material suitable for enteral or parenteral administration. The pharmaceutical preparations can be in solid form or in liquid form.



  They may contain auxiliaries, such as preservatives, stabilizers, wetting agents or emulsifiers, salts for changing the osmotic pressure or buffers.



  They can also contain other therapeutically valuable substances.



   Example 600 mg of 17-ethynyl-19-ethyl-17P-hydroxyandrost-4-en-3-one are dissolved in 24 ml of acetic anhydride, 300 mg of p-toluenesulfonic acid are added and the mixture is stirred under argon at room temperature overnight. The reaction mixture is poured onto ice-cold sodium bicarbonate solution, stirred for one hour, extracted with ether and the extracts are washed 4 times with saturated bicarbonate solution and once with water. After adding a few drops of pyridine, it is dried over sodium sulfate and the solvent is evaporated off. The residue is chromatographed on 50 times the amount of silica gel with hexane / acetone 5: 1. 350 mg of 17a-ethynyl-19-ethyl-3,17-diacetoxy-androsta-3,5-diene, which melts at 181 to 1840 after crystallization from acetone / hexane, are obtained.

  UV: E232 = 18650; (z] 2s9 2030 (c = 0.1 in dioxane).

 

Claims (1)

PATENTANSPRUCH PATENT CLAIM Verfahren zur Herstellung von 19-Alkylsteroiden der Formeln EMI2.1 EMI2.2 <tb> <SEP> TL <SEP> P2 <tb> <SEP> .C <SEP> J <tb> Acht <SEP> 4 <SEP> ¯ <tb> worin Rt Wasserstoff oder Cl ,;-Alkyl, R2 Hydroxy, Acyl- oxy oder Cl 6-Alkoxy und R3 Wasserstoff, C1 6-Alkyl oder C2 6-Alkinyl darstellen, dadurch gekennzeichnet, dass man eine Verbindung der allgemeinen Formel EMI2.3 oder ein A6-Dehydroderivat davon enolverestert. Process for the preparation of 19-alkyl steroids of the formulas EMI2.1 EMI2.2 <tb> <SEP> TL <SEP> P2 <tb> <SEP> .C <SEP> J <tb> Eight <SEP> 4 <SEP> ¯ <tb> in which Rt is hydrogen or Cl, - alkyl, R2 is hydroxy, acyloxy or Cl 6 -alkoxy and R3 is hydrogen, C1 6 -alkyl or C2 6-alkynyl, characterized in that a compound of the general formula EMI2.3 or an A6 dehydro derivative thereof is enolesterified.
CH1782470A 1968-05-15 1969-04-25 19-alkyl steroids CH507923A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CH1782470A CH507923A (en) 1968-05-15 1969-04-25 19-alkyl steroids

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CH720068A CH502327A (en) 1968-05-15 1968-05-15 Process for the preparation of 19-alkyl steroids
CH1782470A CH507923A (en) 1968-05-15 1969-04-25 19-alkyl steroids

Publications (1)

Publication Number Publication Date
CH507923A true CH507923A (en) 1971-05-31

Family

ID=4321433

Family Applications (5)

Application Number Title Priority Date Filing Date
CH720068A CH502327A (en) 1968-05-15 1968-05-15 Process for the preparation of 19-alkyl steroids
CH1782270A CH507926A (en) 1968-05-15 1968-05-15 19-alkyl steroids
CH1782470A CH507923A (en) 1968-05-15 1969-04-25 19-alkyl steroids
CH1782370A CH507925A (en) 1968-05-15 1969-04-25 19-alkyl steroids
CH1782570A CH524585A (en) 1968-05-15 1969-04-25 19-alkyl steroids

Family Applications Before (2)

Application Number Title Priority Date Filing Date
CH720068A CH502327A (en) 1968-05-15 1968-05-15 Process for the preparation of 19-alkyl steroids
CH1782270A CH507926A (en) 1968-05-15 1968-05-15 19-alkyl steroids

Family Applications After (2)

Application Number Title Priority Date Filing Date
CH1782370A CH507925A (en) 1968-05-15 1969-04-25 19-alkyl steroids
CH1782570A CH524585A (en) 1968-05-15 1969-04-25 19-alkyl steroids

Country Status (9)

Country Link
AT (1) AT290027B (en)
BE (1) BE733017A (en)
CH (5) CH502327A (en)
DE (1) DE1924785A1 (en)
ES (1) ES367281A1 (en)
FR (1) FR2008589A1 (en)
GB (1) GB1269234A (en)
IL (1) IL32151A0 (en)
NL (1) NL6907136A (en)

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
BE632012A (en) *

Also Published As

Publication number Publication date
CH524585A (en) 1972-06-30
GB1269234A (en) 1972-04-06
CH507926A (en) 1971-05-31
FR2008589A1 (en) 1970-01-23
IL32151A0 (en) 1969-07-30
ES367281A1 (en) 1973-03-16
DE1924785A1 (en) 1969-11-20
NL6907136A (en) 1969-11-18
BE733017A (en) 1969-11-14
CH507925A (en) 1971-05-31
CH502327A (en) 1971-01-31
AT290027B (en) 1971-05-10

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