GB874214A - Improvements in or relating to steroids and the manufacture thereof - Google Patents

Abstract

The invention comprises a compound having the formula: <FORM:0874214/IV (b)/1> wherein R is methyl or hydrogen, R2 is hydrogen or the acyl radical of a hydrocarbon carboxylic acid containing from 1-12 carbon atoms inclusive, R1 is an alkyl radical containing from 1-6 carbon atoms inclusive or an alkinyl radical of the structure -C=CR3 in which R3 is hydrogen or an alkyl radical containing 1-4 carbon atoms inclusive, a compound having the formula: <FORM:0874214/IV (b)/2> wherein Y is hydroxy or keto and a process which comprises reacting 3b ,17b -dihydroxy-17a -alkyl-5-androstenes (or 19-norandrostenes) with a peracid to obtain 3b ,17b -dihydroxy-17a -alkyl-5a ,6a -epoxyandrostanes (or 19-norandrostanes); treating said 5a ,6a -epoxy compounds with hydrogen fluoride to obtain 6b - fluoro - 3b ,5a ,17b - trihydroxy - 17a - alkyl androstanes (or 19-norandrostranes), oxidising these compounds to 6b -fluoro-5a ,17b -dihydroxy-17a -alkyl-androstan-3-ones (or 19-norandrostanes); dehydrating said 6b -fluoro-5a -hydroxy compounds to obtain 6b -fluoro-17b -hydroxy-17a -alkyl-4-androsten-3-ones and 6b -fluoro - 17b -hydroxy-17a -alkyl-4-(19-norandrosten)-3-ones. The 6b -compounds may be epimerised to the 6a -compound by means of an acid or base. 17 - acylates are obtained by the usual methods. In another method 17b - hydroxy-17a -alkyl-4-androsten-3 - one (or 19 - norandrosten) is treated with ethylene glycol to obtain a 3-ethylene ketal which with a peracid gives 17b -hydroxy-17a -alkyl-5a ,6a -epoxyandrostan-3-one 3-ethylene ketal; said 5a ,6a -epoxy compound is treated with hydrogen fluoride to obtain 6b -fluoro-5a ,17b -dihydroxy - 17a - alkylandrostan-3-one and 6b -fluoro-5a ,17b -17a -alkyl-19-norandrostan-3-one. Illustrative products of the invention are 6a and 6b -fluoro-17b -hydroxy-17a -methyl-4-androsten-3-one and the 17-acetates thereof, 6b -fluoro-3b ,5a ,17b -trihydroxy-17a -methyl and 17a -ethylandrostane, 6b -fluoro-5a ,17b -dihydroxy-17a -methyl and 17a -ethyl-androstan-3-one, 6a and 6b -17b -hydroxy-17a -ethinyl-4-androsten-3-one and the 17-acetate thereof. Specification 755,129 is referred to.ALSO:Pharmaceutical compositions comprise compounds having the formula <FORM:0874214/VI/1> wherein R represents methyl or hydrogen, R2 represents hydrogen or an acyl radical of a hydrocarbon carboxylic acid containing from 1-12 carbon atoms, inclusive, and R4 represents a lower aliphatic hydrocarbon radical, and a pharmaceutical diluent. These compounds are administered orally as pills, tablets, capsules, syrups, or elixirs or in liquid forms for injectable products. Oestrogens, e.g. ethinylestradiol, may also be present. Specification 755,129 is referred to.