CH194979A - Method for the preparation of 17-methyl-dihydrofollicle hormone. - Google Patents

Description

  

  Method for the preparation of 17-IIIethyl-dihydrofollicle hormone. The present invention relates to a method for the preparation of 17-methyl-dihydrofollicle hormone, which is characterized by the fact that a compound which is derived from the follicle hormone of the formula Cl $ H220.> Is derived in that it is a radical in place of the hydroxyl group be seated, which is replaced by the hydroxyl group on hydrolysis, z.

   B. an ester or ether group or halogen, with an organometallic compound suitable for converting ketones into methyl carbinols.

   For example, according to the Grignard method with methyl magnesium iodide, the organometallic reaction product thus formed splits up with the aid of hydrolysing agents and then the group in place of the hydroxyl group of the follicle hormone is converted into the hydroxyl group by hydrolysis.

   When working up the reaction mixture, 17-methyldihydrofollicle hormone of the formula C11112602 is then obtained in crystalline form.



  The process according to the invention is illustrated below with reference to, for example, given formula pictures in which with R a group which can be converted into the hydroxyl group by hydrolysis, for example an ester or ether group or halogen
EMI0001.0032
  
    C113 <SEP> indicates <SEP> is:

   <SEP> C118 <SEP> CH,
<tb>,: 0 <SEP> i "OH
<tb> (O
<tb> CH3Mg <SEP> J
<tb> R1
<tb> __HO hydrolysis <SEP> derivative <SEP> of the <SEP> follicle hormone <SEP> 17-methyl-dihydrofollicle hormone
<tb> Ci <B> 811 </B> 2.O2 <SEP> Ci9H2r, 0s The organometallic compounds that are suitable for the conversion of ketones into methyl carbinols and are suitable for the conversion of ketones into methyl carbinols are for example in their use described in Houben-Weyl, Methods of Organ. Chemie, Volume 3, 2nd edition (1923), page 61 ff.



  <I> Example: </I> To an ethereal solution of methyl uragnesium iodide, prepared from 4 g of dry magnesium shavings, 12.5 cm of methyl iodide and 160 cm of dry ether in the presence of a trace of iodine, a solution of Gradually add 5 g of follicular hormone benzoate from melting point 216 to 22.0 in 150 cm '<B>' </B> dry benzene:

  sweet. After the addition of the benzoate solution, the reaction liquid is heated to boiling for about 111 hours, then, after cooling, it is decomposed with water and dilute hydrochloric acid (1: 5) with ice cooling and taken up in ether. The ethereal solution is washed one after the other with water, aqueous sodium thiosulphate solution and again with water, dried and evaporated.



  The residue obtained is soaped off by heating with 5% methyl alcoholic potassium hydroxide solution for 3 hours on a steam bath.

   After cooling, the saponification solution is diluted with water, acidified with dilute hydrochloric acid (1: 5), extracted with ether and the ethereal solution extracted successively with dilute soda solution (to remove the benzoic acid) and then thoroughly with 5% aqueous potassium hydroxide solution .

   After acidifying the potassium hydroxide extracts, the methyl @d: hydrofollicle hormone separates in crystalline form and can be isolated by filtration or absorption in ether. Almost quantitative yield.



  The reaction product obtainable according to the process is new; According to the theory, it consists of a mixture of two stereoisomeric methyl carbinols and, in concentrated sulfuric acid, shows a blue-green color and fluorescence in the light of the analysis quartz lamp.

   The physiological effect value of the preparation in the Allen-Doisy test is 3 to 4 million rat units per gram when administered subcutaneously in an aqueous solution and subdivided six times, while the follicular hormone of the formula C1gH2202 is only about one full 1.2 million Ratterreinlreitull I110 grams.

 

Claims (1)

PATENT CLAIM: Process for the preparation of 17-methyl dihydrofollicle hormone of the formula C "H2" 02, characterized in that a compound is derived from the follicle hormone of the formula C181122-02 in that it has a residue in place of the hydroxyl group which is replaced by the hydroyl group on hydrolysis, with an organometallic compound suitable for converting ketones into methyl carbinols, splitting the organometallic reaction product formed with the aid of hydrolysing agents and then converting the group in place of the hydroxyl group of the follicle hormone into the hydrogyl group by hydrolysis. The new crystalline compound, the 17-ITethyldihydrofollicle hormone of the formula C12112102, has an increased effectiveness of about 3 to 4 million rat units per gram in Allen-Doisy compared to the follicle hormone of the formula C18112202 with an effectiveness of about 1.2 million rat units per gram -Test. SUB-CLAIM 1. Method according to patent claim, characterized in that the metal-organic compound used is methyl magnesia halide. 2. Process according to patent claim and sub-claim 1, characterized in that methylmagnesium ioidide is used as the organometallic compound. Process according to claim, characterized in that an ester of the follicular hormone is used.