Patent GB-1027268-A (GB)
Title: New methyl-androstenes and process for their manufacture
IPC: A61K31/569
Filed: 1964-05-04
Abstract: The invention comprises steroids of the formula <FORM:1027268/C2/1> (wherein R1 is H or Me, R2 is a free, esterified or etherified hydroxyl group, and R3 is H or a saturated or unsaturated unsubstituted or halogenated aliphatic hydrocarbon group of at most 6 carbon atoms, or R2 and R3 together may be a free, ketalized or enolized oxo group) and their preparation by dehydrogenation of corresponding ring A saturated steroids by bromination and dehydrobromination, or by oxidation of corresponding 3-hydroxy steroids by means of a compound of hexavalent chromium or tetravalent manganese, or by the Oppenauer method.  If desired a hydroxyl group may subsequently be esterified or etherified, or an esterified or etherified hydroxyl group or ketalized or enolized oxo group liberated, and/or a 17-oxo group converted, if desired with temporary protection of the 3-oxo group, into a hydroxyl group or a hydroxyl group and a hydrocarbon group of the type specified above, and if desired the so-formed hydroxyl group may be esterified or etherified. A protected 3-oxo group may, for example, be formed by converting D 1 - 3,17 - dioxo - 7a  - methyl - 5a -androstene into D 1 - 3 - oxo - 7a  - methyl - 17b -hydroxy - 17a  - cyano - 5a  - androstene, converting this to the 3-anol ethyl ether, and treating with a basic agent to give the corresponding 17-ketone, which may then be converted into the 17a  - hydrocarbon - 17b  - ol and the 3-keto group regenerated.  Examples are given, in one of which dehydrobromination of 2-bromo-3-oxo - 7a ,17a  - dimethyl - 17b  - hydroxy - 19-nor-5a -androstane gives, as well as the required D 1 - compound, some D 4 - 3 - oxo - 7a ,17a -dimethyl - 17b  - hydroxy - 19 - nor - androstene.  Ring A saturated steroids used as starting materials are prepared by reduction of the corresponding D 4-3-oxo-steroids, themselves prepared, for example, from 7-unsubstituted-D 5-3-hydroxy-steroids by Oppenauer oxidation, dehydrogenation to D 4 6 - 3 - oxo - steroids and subsequent treatment with methyl magnesium bromide in the presence of a copper salt.  D 1-3-hydroxy - 7a  - methyl - 17 - oxo - 5a  - androstene is prepared by ketalization of D 5-3-hydroxy-17-oxo-androstene to give the 17-ethylene ketal, conversion of this by the aforementioned methods to D 1 - 3 - oxo - 7a  - methyl - 17 - ethylenedioxy - 5a  - androstene, reduction to D 1 - 3-hydroxy - 7a  - methyl - 17 - ethylenedioxy - 5a -androstene and hydrolysis of this.  The product can then be converted to the corresponding 17a  - allyl - and 17a  - ethynyl - 17b  - hydroxy-compounds.  The 7a -methyl-steroids of the invention, which are variously stated to have anabolic and antigonadstrophic action, and to act as gestagens and ovulation inhibitors, may be made up into pharmaceutical or veterinary compositions with suitable carriers. These may take the form of solutions, suspensions, emulsions, depot preparations, tablets, dragees, ointments or creams, and may contain preserving, stabilizing, wetting or emulsifying agents, salts for regulating the osmotic pressure or buffers.