Patent GB-1041279-A (GB)
Title: 13-alkyl steroid ketones
Inventor: HUGHES GORDON ALAN
IPC: A43B3/12
Filed: 1961-10-19
Abstract: Novel steroids of the general formula <FORM:1041279/C2/1> wherein R represents an alkyl group of at least 2 carbon atoms, R2 represents a substituted or unsubstituted alkyl, alkenyl or alkynyl group (a suitable substituent is methoxy) and ring A contains an ethylenic bond terminating at the 5-position, are prepared by hydrolysing a steroid of the general formula <FORM:1041279/C2/2> wherein X represents an acid-hydrolysable protected 3-oxo group, e.g. an alkoxy group such as the methoxy, ethoxy, methoxymethoxy and dihydroxypropyloxy, an alkylthio group such as alkylthio and benzylthio, an acyloxy group such as acetoxy, a dialkylamino group, an N-pyrrolidyl group, an alkylenedioxy group such as ethylenedioxy, an alkylenedithio group, or an alkylenethiooxy group, which is accompanied by an ethylenic bond terminating at the 5-position; by selectively reducing a steroid of the general formula <FORM:1041279/C2/3> wherein R represents an alkyl group and R1 has the above significance (a) by hydrogenation in solution in a non-protonic solvent using a palladium or Raney nickel catalyst to saturate the 14(15)-ethylenic bond, (b) by a carbonyl-reducing reagent such as sodium borohydride or lithium aluminium hydride, before or after the catalytic hydrogenation step to convert the carbonyl group to a hydroxymethylene group, (c) by the action of alkali metal in liquid ammonia after the catalytic hydrogenation and simultaneously with or after the carbonyl-reducing step, to saturate the 8(9)-ethylenic bond, and (d) by the action of alkali metal in liquid ammonia in the presence of a proton donor that is an alcohol having less than 6 carbon atoms, simultaneously with or after the saturation of the 8(9)-ethylene bond to form a steroid of the formula <FORM:1041279/C2/4> selectively oxidizing this compound to the corresponding 17-keto compound, and reacting this compound with an organo-metallic reagent containing the group R2; by ketalizing a corresponding steroid of the formula <FORM:1041279/C2/5> or <FORM:1041279/C2/6> wherein R represents an alkyl group, with an alkylene glycol to form a steroid of the formula <FORM:1041279/C2/7> wherein X represents an alkylenedioxy group and ring B has an ethylenic bond terminating at the 5-position, oxidizing this steroid to the corresponding 17-keto compound, treating the 17-keto compound with an organo-metal ethynylating agent to form the 17a -R2-17b -hydroxy-grouping and hydrolysing the ketal group at the 3-position to form a 4(5)-ethylenic steroid of the first formula above wherein R1 has the above significance and R2 represents an alkynyl group; by oxidizing a corresponding steroid diol of the formula <FORM:1041279/C2/8> having an ethylenic bond terminating at the 5-position, by isomerizing the corresponding steroids having an ethylenic bond in the 5(10)-position under basic or acidic conditions to form the corresponding 4(5)-unsaturated compounds; and by selectively reducing the steroids of the first general formula above wherein R2 is an unsaturated group to form corresponding steroids in which R2 is more saturated, for example by catalytic hydrogenation. The above formulae include all states of resolution except the resolved 13a -enantiomer.  Pharmaceutical compositions which may be administered orally or by injection contain as the active ingredient a steroid of the first general formula above.  The compositions may be used as anabolic agents.