CH201834A - Process for the preparation of a 7-dehydrosterol. - Google Patents

Description

  

  Process for the preparation of a 7-dehydrosterol. It has been found that 7-oxositosterol can be converted into 7-dehydrositosterol if an acyl derivative of 7-oxositosterol is acted upon by a metal alcoholate acting as a mild reducing agent, e.g.

   B. converts an alcoholate of an earth metal, in particular of aluminum, into 7-oxysitosterol while maintaining the double bond and esterifies this to a diacyl derivative, from which the aeyl radical in 7- Position in the form of acid is split off and the resulting monoacyl derivative is saponified.

   The new double bond formed during the cleavage is in the conjugated position to the double bond that was already present in the 5,6-position of the starting material.

   In ring B of the sitosterol containing the keto group, the reactions described above take place according to the following reaction scheme:
EMI0001.0035
    The previously unknown 7-dehydrositosterol which is obtainable in this way forms crystals with a melting point of 148 to 150 '. It can be precipitated with digitonin, sparingly soluble in methyl alcohol, easily soluble in ether. It has an absorption spectrum that is almost the same as that of ergonene. It should be used as a starting material for the manufacture of anti-inflammatory products.

             Example: To obtain 7-oxositosterol, whoever dissolved 100 g of sitosterol acetate in 5 liters of hot glacial acetic acid, after cooling to 50 to 60, added 90 g of chromic anhydride in glacial acetic acid and held at 50 to 60 for 5 hours. The glacial acetic acid solution is concentrated to about 300 cm 'under reduced pressure, the residue is extracted with ether and the ether extract is freed from acidic components by shaking with sodium carbonate solution. The ether extract is concentrated to a small volume and methanol is added until the start of crystallization.

   The crude product is recrystallized from ether-methanol. The 7-oxositosterol acetate melts at 154, crystallizes in flakes, is easily soluble in: ether and acetone, sparingly soluble in methyl alcohol.



  To convert to 7-oxy-sitosterol, 25 g of 7-oxositosterol acetate are dissolved in 250 cm "of dry isopropyl alcohol, 10 g of aluminum isopropylate are added and the mixture is heated to the boil for 5 hours on the reflux condenser.

    After the reduction is complete and the acetyl group is split off at the same time, the solution is poured into about 3 liters of 0.5% aqueous sodium hydroxide solution and the flaky reduction product is filtered off, the precipitate is dissolved in ether, filtered again, the ethereal solution is evaporated to about 100 cm ' and offset with. 300 a petroleum ether, during which the crude 7-oxy-sitsterin is deposited in the form of small gelatinous balls.



  To prepare 7-oxysitosterol dibenzoate, 20 g of 7-oxysitosterol are dissolved in 150 cm of pyridine, 5 cm of benzoyl chloride are added and the mixture is left to stand for 15 hours at room temperature. The pyridine solution is diluted with ether-water, the ether extract is freed from pyridine using dilute hydrochloric acid, washed acid-free and dried over sodium sulphate. and narrowed to about 50 cm.

   If the ethereal solution is mixed with methanol until it starts to become cloudy, the dibenzoate separates out in fine needles. After recrystallization from ether - methanol or acetone - 31ethanol, the 7-oxy-sitosterol-diben- delt melts at 15511.



  To convert it into the 7-dehydrositosterol benzoate, 7-oxv-sitosterol dibenzoate is heated in portions of 1 g each in a high vacuum to 1.75 for 1/2 hour. Benzoic acid and oily components go over. The heating residue is dissolved in ether. the essential solution is concentrated to a small volume. and mixed with methanol until cloudy.

   The deposited monobenzoate is recrystallized from ether methyl alcohol for further purification. The dehydrositosterol benzoate crystallizes in needles and melts at 144 to 146.



  To obtain the 7-dehydrositosterol, 1 g of 7-dehydrositosterol benzoate is dissolved in 1.0 cm: 'of hot benzene and 30 cm of 5% sodium methylate solution is added at boiling point, then the solvent is distilled up to Start of crystallization, i h. For further purification, one crystallizes from - # - tlier-ethyl alcohol. The 7-Dehy cirositosterol crystallizes in large leaflets.

    melts at 148 to 150, is easily soluble in ether, very sparingly soluble in methyl or ethyl alcohol. It can be precipitated with digitonin; when antimony trichloride is added to a chloroform solution, it turns red immediately, which turns blue after standing for a while. The absorption spectrum is almost that of ergosterol. equal.

 

Claims (1)

PATENT CLAIM: A process for the preparation of a 7-De- 1 <<#drosterol, characterized in that an acyl derivative of 7-oxositosterol is converted into 7-oxy - sitosterol by the action of a metal alcoholate acting as a mild reducing agent, the latter being esterified to a diacyl derivative , from this by heating the acyl radical in the 7-position is split off in the form of acid and the resulting monoacyl derivative is saponified. 7-Dehydrositosterol, which has not yet been described in this way, forms crystals with a melting point of 148 to 150. t1NTERANSPRt1GITE 1. Method according to claim, characterized in that alcoholates of earth metals are used as mild reducing agents. 2. Method according to patent claim and sub-claim 1, characterized in that an aluminum alcoholate is used as the reducing agent. 3. The method according to claim and sub-claims 1 and 2, characterized in that aluminum isopropoxide is used as a reducing agent. 4. The method according to claim, characterized in that one starts from 7-ogositosterol acetate. Process according to patent claim, characterized in that the dibenzoate thereof is produced as the diacyl derivative of 7-ogysitosterol.