Patent GB-455378-A (GB)
Title: Process for the production of androsterones
IPC: C07J75/00
Filed: 1935-03-16
Abstract: Saturated or unsaturated diketones of the cyclopentanopolyhydrophenanthrene series are converted by hydrogenation into the corresponding saturated hydroxy ketones of the formula C19H32O2.  The hydrogenation is effected under such conditions of temperature and pressure that only one keto group is reduced, while at the same time the nuclear double bond (if present) is saturated.  Suitable conditions of reduction are described in Houben-Weyl, "Methoden der Organischen Chemic 1925," vol. 2, page 245 et seq.  The reactions of the present invention do not, however, always proceed quantitatively in one direction, and a separation of the reaction products is consequently necessary.  The preferred reducing agent is catalytically activated hydrogen in the presence of weak catalysts at low temperature.  The amount of hydrogen used and the hydrogen ion concentration of the solution require careful regulation.  In accordance with the Auwers Skita rule the cis form of the hydroxy ketone is produced by reduction in acid solution, and the trans form by reduction in neutral or alkaline solution.  The starting materials for the present invention may be prepared by the oxidation of the corresponding hydroxy ketones.  The process thus affords a method for the epimerization of hydroxy ketones of the cyclopentanopolyhydrophenanthrene series, and the convertion of synthetic hydroxy ketones of low physiological activity into isomeric compounds of high physiological activity which could hitherto only be obtained in small quantities from natural sources, such as the urine of male individuals.  In examples: (1) trans androsterone obtained synthetically by the oxidation of sterols is oxidized with chromic acid in acetic acid solution at room temperature to produce androstandione.  This is then reduced in glacial acetic acid solution with hydrobromic acid in the presence of platinum black and in a hydrogen atmosphere at 70--75 DEG  C.  The trans-androsterone produced simultaneously in small amount is removed by precipitation with digitonin.  The cis-androsterone is recrystallized from alcohol. The reduction may also take place in alcoholic solution, and in this case the temperature used is 50--60 DEG  C.; (2) dehydro-androsterone is treated with bromine in glacial acetic acid solution, and then oxidized with chromic acid overnight at room temperature.  The product is debrominated by treatment with zinc dust and the p resulting androstendione recrystallized from alcohol.  The reduction to cis-androsterone is effected in two stages.  First a solution of the androstendione in glacial acetic acid is treated with hydrogen in the presence of platinum black at room temperature to saturate the nuclear double bond, and then a further amount of acetic acid containing a small amount of sulphuric acid is added and the hydrogenation continued until a further molecule of hydrogen has been taken up.  The product is worked up as in example (1); (3) androstandione is reduced in alcoholic solution in the presence of platinum oxide by shaking with hydrogen at room temperature until one molecule of hydrogen has been taken up.  The catalyst is filtered and the product worked up as in example (1).  Specifications 435,563, 447,185, and 448,225 are referred to.