CH507923A - 19-alkyl steroids - Google Patents

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

  

  
 



  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)

PATENT CLAIM 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.