DESC010192MA - - Google Patents

Description

FEDERAL REPUBLIC OF GERMANY

Registration date: August 8, 1952. Advertised on October 20, 1955

GERMAN PATENT OFFICE

In the German patent 881 945 is among other things described the production of therapeutically valuable alcohols of the cyclopentanopolyhydrophenanthrene series,

which in the 3-position the grouping "> and in

the 17-position the grouping

R ²

₃ ^

HO ⁷
own, where

R ^{1 is} a saturated or unsaturated aliphatic hydrocarbon radical, R ^{2 is} hydrogen or a saturated or unsaturated hydrocarbon side chain with ι to 3 carbon atoms, the hydrogens of which can be completely or partially replaced by hydroxyl, O-acyl, carbonyl or oxide oxygen, R ³ an OH group or a group which can be converted into an OH group or, if R ^{2 is} not hydrogen, can be hydrogen, or R ² + R ³ together can mean a carbonyl oxygen.

The compounds mentioned were prepared according to the process of the main patent by reacting 3-keto compounds which contain the aforementioned grouping R ^{2 in the 17-position}

₃ )>, where R ^{3 is} also one in a HO group

Can be convertible group with organometallic compounds.

It has now been found that the same compounds, in which, however, restrictively compared to the main patent R ^1, a saturated or unsaturated

509 576/43

Sch 10192 IVc / 12 ο

ten Kohlcmvasscrstofirest, R ^{2 is} a saturated or unsaturated hydrocarbon side chain with ι to 3 carbon atoms and R ³ should mean an OH group, also starting from Cyclopentanopolyhydrophenanthreiien, which in the 3-position

grouping

where OH is also replaced by an in

Oll-transferable group can be replaced, and the have a keto group in the 17-position by reaction with organometallic compounds, such as alkyl! magnesium halide!, lithium alkyls or Alkalicetyliden, can produce in a known manner.

Such compounds have, preferably when R- and R ^{1 are} different and in particular when R- is an unsaturated hydrocarbon side chain, such as ethynyl, a strong inhibitory effect on the testicular growth of young male rats.

The method according to the invention offers opposite The process of the main patent has certain technical advantages: While in the implementation of 3-keto compounds always two positional isomers are formed with the organometallic compounds, the are often not easy to separate, the analogous conversion of the 17-keto compounds proceeds sterically almost uniform, so that difficult separations are no longer necessary.

W. I). As part of a work on dipole moments of steroids (Journ. Amer. Chem.-Soc, Vol. 07, iij-15, pp. 1901 to 1906) already certain physical properties of two crystal fractions of one. "3, i7-Dimethylandrostandiols-3, i7«>. ' communicated, but no information was given about the process by which his test material was produced had been, for the production of which there is no other verifiable information in the specialist literature can be found. The method according to the invention therefore also means compared to the known state technology, which allowed only vague assumptions about the accessibility of the process products unambiguous progress.

The next quick examples explain the invention Proceedings.

Example 1

3b-M <'thyl-17'i-ethinyllandrostane-3, 17-diol

10 g of potassium are added to approximately _^3/4 1 of liquid ammonia at about -70 to -60 "Hadtemperatur; then potassium acetylene is introduced until complete reaction then allowed a solution of 10 g of 3b-methylandrostane-3-ol. i7-on

in 150 ecm dry ether and 150 ecm dry Dioxane flow in and flush with about 150 ecm dry Ether after. Then the reaction vessel is removed from the cold bath and remains overnight stand at barely any temperature. The next morning the reaction mixture is mixed with 200 ecm of dioxane, decomposed under ice-cooling with water and then with dilute sulfuric acid. The precipitated raw conversion product is sucked off and washed neutral.

After repeated recrystallization from ethyl acetate, the pure 3b-methyl-i7a-ethinylandrostane-3,17-diol melts at 210 to 211 ⁰ ; [a] _D = -30 ° (dioxane).

Example 2

-s, 17-diol

In an analogous manner, 10 g of 3 a-methylandrostan-3-01-17-one are reacted and worked up. After the decomposition with dilute sulfuric acid, ether is extracted, the ether solution washed neutral, shaken with soda solution and washed neutral again. The dried ether solution is evaporated and the remaining residue is dissolved in warm methanol. After prolonged standing in the cold, the 3a-methyl-i7a-äthinylandrostan-3, 17-diol crystallizes out. After recrystallizing twice from hexane-ether, the substance is pure and melts at 163 to 164 ⁰ ; Md = -29.2 ° (dioxane).

Example 3
3 a, i7ct-dimethylandrostane-3,17-diol

A solution of 5 g of 3α-methylandrostan-3-01-17-one in 100 ecm of ether was added dropwise to an ethereal methylmagnesium iodide solution (of 3 g of magnesium, 10 ecm of methyl iodide and 100 ecm of ether). Then yet I ¹ Z was heated for ₂ hours to boiling and decomposes the cooled to room temperature reaction mixture with water and dilute sulfuric acid. The undissolved portion of the reaction product was brought into solution by adding ether and the solution was washed successively with water, thiosulfate solution and again with water. After repeated recrystallization from acetone, the residue remaining on evaporation of the ether is used to obtain 3 a, i7 "-dimethylandrostane-3,17-diol with a melting point of 206 ° to 208 °.

Example 4
3b, i7a-dimethylandrostane-3, 17-diol

5 S 3b-Meth.ylandr.ostan-3-ol-1.7-one are reacted in an analogous manner with methyl magnesium iodide and worked up. After recrystallization from methanol and ethyl acetate, the crude reaction product gives 3 b, 17-dimethylandrostane-3,17-diol with a melting point of 215 to 217 ^° . no

Claims (1)

PATENT CLAIM: Process for the preparation of alcohols of the cyclopentanopolyhydrophenanthren series, which are described in Rl the 3-position the grouping ^ and in the 17 position contains the grouping ₃ )>, in where R ^{1 is} a saturated or unsaturated hydrocarbon radical, R ^{2 is} a saturated or unsaturated hydrocarbon side chain with 1 to 3 carbon atoms and R ^{3 is} an OH group, according to patent 881 945, characterized 576/43 Sch 10192 IVc / 12 ο draws that connections of the same series, Rl the grouping in the 3-position)>, in the OH R ^{1 has} the meaning given above and the O H group can also be replaced by a group which can be converted into an O H group and which have a keto group in the 17-position, used as starting compounds. Referred publications: German Patent Nos. 643 978, 681 869; Swiss patent specification No. 189 749.