GB893146A - Improvements in or relating to steroids and the manufacture thereof - Google Patents

Abstract

The invention comprises compounds having the formulae <FORM:0893146/IV (b)/1> <FORM:0893146/IV (b)/2> <FORM:0893146/IV (b)/3> <FORM:0893146/IV (b)/4> <FORM:0893146/IV (b)/5> wherein R is hydrogen or methyl, R1 is an alkyl radical containing from 1-8 carbon atoms, inclusive, R2 is hydrogen or the acyl radical of an organic carboxylic acid, Y is hydrogen or fluorine, X is b > CHOH or > C = O and Z is bromine iodine, and a process which comprises treating a 17b -hydroxy-17a -alkyl-11-oxygenated-4-androsten-3-one with a diol to form a 17b -hydroxy - 17a - alkyl - 11 - oxygenated - 4 - androsten-3-one 3-ketal, which may be reduced, if desired, to obtain an 11b -hydroxy compound, epoxidising said ketal with a peracid to produce a 5a ,6a -epoxy-compound which, on treatment with hydrofluoric acid, gives 6b -fluoro-5a ,17b -di-hydroxy - 17a - alkyl - 11 - oxygenated - andros - tane-3-one. O treatment with hydrochloric acid this compound gives 6a -fluoro-17b -hydroxy-17a - alkyl - 11 - oxygenated - 4 - androstene - 3 - one. The 17-hydroxy group may be esterified by the usual means. In an alternative method a 9-fluoro atom is introduced into 6a -fluoro-11,17b -dihydroxy - 17a - alkyl - 4 - androsten - 3 - one by a reaction scheme which involves forming a 9(11)-dehydro compound, a 9-bromo or iodo compound, and a 9(11)-epoxy compound which with hydrogen fluoride gives the desired 9a -fluoro compound. These processes are also applicable to the 19-nor compounds. Illustrative products of the invention are 6a -fluoro-17b -hydroxy - 17a - methyl - 4 - androstene - 3, 11 - dione, 6a - fluoro - 11b , 17b - dihydroxy - 17a - methyl - 4 - androstene - 3 - one, 6a , 9a - difluoro - 17b - hydroxy - 17a - methyl - 4 - androstene - 3, 11 - dione, 6a , 9a - difluoro - 11b , 17b - di - hydroxy - 17a - methyl - 4 - androstene - 3 - one, the 17-propionates thereof, and the corresponding 5a -hydroxy-androstanes. Specifications 750,941 and 806,045 are referred to.ALSO:Pharmaceutical compositions comprise a compound of the formula <FORM:0893146/VI/1> wherein R is hydrogen or methyl, R1 is an alkyl radical containing from 1-8 carbon atoms inclusive, R2 is hydrogen or the acyl radical of an organic carboxylic acid, Y is hydrogen or fluorine, and X is b -hydroxymethylene or keto and a pharmaceutical diluent. They are employed orally as pills, tablets, capsules, syrups or elixirs or in liquid forms for injection. Specifications 750,941 and 806,045 are referred to.