DE731191C - Process for the preparation of derivatives of the nucleus-saturated and unsaturated-Pregnan series - Google Patents

Description

Process for the preparation of derivatives of the nucleus saturated and unsaturated Pregnan series It has been found that derivatives of the saturated and unsaturated Pregnan series can be achieved if one uses the semicyclic in a manner known per se Double bond of 17, 2o-unsaturated aldehydes of this series, their aldehyde group is in the 2r position, with free or substituted hydroxyl groups or but is saturated with oxygen and in the latter case the oxides thus obtained are hydrolyzed.

The starting materials can be of any steric configuration, arbitrarily substituted and saturated or unsaturated in the core. Existing core double bonds as well as sensitive substituents such. B. aldehyde or hydroxyl groups optionally protected as an intermediary in a conventional manner, e.g. B. by saturation with halogens or hydrogen halides, by acetalization or by esterification or etherification.

According to experience, one uses to saturate the beic_vclic Double bond of the starting materials, for example Wasserz21 d and its derivatives, such as organic and inorganic peracids or also peroxides, osmium tetroxide, silver salts in the presence of halogen or already formed halogen complexes of silver salts, free or esterified hypohalous acids, hydrohalic acids, sulfuric acids, as well as free halogens or pseudohalogens. You may work in the presence of catalysts. In this way one obtains aldehydes, in the 17, 2o-position an ethylene oxide group or. in the 17- and / or 2o-position free and / or contain substituted hydroxyl groups. On such prevention, the ethylene oxide groups have, one then lets h_vdrol_v: beer-giving agents act.

The end products can be used therapeutically as such, because they have the effect of renal cortex hormones or as intermediates serve to produce therapeutically utilizable compounds. Example i 1.6 parts i `r% # - '° -Pregnadien-3-one-.2i-al" -erden dissolved in 15 parts of absolute methyl alcohol and with 0.8 parts of orthoformic acid ester and o, o: parts of ammonium nitrate at reflux warmed up. The reaction solution is completely freed from the solvent in vacuo. 1Zan takes up the acetal formed in 250 parts of ether, mixed with 1.3 parts Osrniumtetroxyd and lets the solution stand for a long time at room temperature. Of the The precipitate formed is filtered off, washed with ether and then divided into 70 parts a 15% sodium sulfite solution in 20% alcohol for 2 hours on Refluxed. The sodium sulfite formed is then suctioned off and concentrated the filtrate in vacuo, the oily residue is taken up in chloroform and washed with water. The chloroform solution is freed from the solvent and the residue heated with 2N hydrochloric acid in 700% alcohol for some time, which cleaved the acetal will. After cooling, it is neutralized, most of the alcohol in the Removed vacuum at 35 ° and extracted the concentrated solution with ether. The ethereal The extract is washed with water and dried. After removing the solvent the remaining @ 4 # 5-Pregnen-i7, 2o-diol-3-on-2i-al by dissolving from methanol cleaned. Yield 23 ° / °.

The 2 i acetal used as starting material des ", i.5,, -1" 2 () - Pregnadien-3-on-2i-als can also be obtained by acetalizing the J5.6 17.20 -3-acetoxy pregnadien-2 i-as, alkaline saponification of the ester group and oxidation of the 3-hydroxyl group z. B. tnit prepare a ketone in the presence of a metal alcoholate.

EXAMPLE A solution of 1.8 parts, 1 ', 2 ° -3-Acetoiypregnen-21-al in 8 parts of absolute alcohol is refluxed for 30 minutes with 0.8 parts of orthoformic acid ester and 0. oi parts of ammonium chloride. Most of the alcohol is then distilled off in vacuo, water is added and the residue is etched out. The dried ether residue is taken up in 75 parts of chloroform, cooled to 0 °, treated with 0.76 parts of benzoperic acid, dissolved in chloroform, and left to stand for 12 hours at 0 'and then for some time at room temperature. When the reaction has ended, it is washed with 2N atron lye and water. removes the chloroform in vacuo, the residue is taken up with i ° / ° potassium carbonate solution in go ° / ° methanol. heated for 30 minutes for the purpose of saponifying the acetate, then mixed with aqueous hydrochloric acid and heated again. After cooling, a lot of water is added, the extract is etched and the i 7,2o-oxy dope egnan-3-o1-2 i-al is isolated from the ethereal extract, which is purified by recrystallization from aqueous alcohol. By heating in an autoclave with aqueous dioxane, the 17,2o-dioxypregnan-3-01-2i-al can be obtained therefrom in a yield of ii ° / °.

If the starting material contains free hydroxyl groups, they can also be protected intermediately by etherification.

Claims (1)

Claim: Process for the preparation of derivatives of the nucleus-saturated and -unsaturated Pregnane series, characterized in that one in all gotiter way -the semicyclic double formation of 17,20-unsaturated aldehydes of this series, the aldehyde group of which is in the 2i-position, with free or substituted hydroxyl groups or saturated with oxygen, optionally with temporary protection of existing double bonds and sensitive substituents. and in the latter case hydrolyzed the oxides thus obtained.