Patent GB-941634-A (GB)
Title: Improvements in or relating to steroids and the manufacture thereof
IPC: C07J75/00
Filed: 1961-10-16
Abstract: The invention comprises 7-methyl-testosterones having the formulae: <FORM:0941634/C2/1> <FORM:0941634/C2/2> <FORM:0941634/C2/3> <FORM:0941634/C2/4> wherein R1 is hydrogen, a - or b -hydroxy, a -acyloxy, or keto, R is b -hydroxy, a -methyl-b -hydroxy, a -methyl-b -acyloxy or b -acyloxy, X is hydrogen, fluorine, chlorine, bromine or iodine and C is >C=O or <FORM:0941634/C2/5> wherein R111 is hydrogen or a lower aliphatic hydrocarbon radical and Y is hydrogen or acyl wherein the acyl radical is that of a hydrocarbon carboxylic acid containing 1-12 carbon atoms, a 7a -methyl 17a -alkynyl testosterone having the formula <FORM:0941634/C2/6> wherein R is hydrogen, methyl or ethyl, and R1 is hydrogen or acyl and acyl is as defined above, 7a -methyl-17a -ethyltestosterone and 17-acylates thereof, a compound having the formula: <FORM:0941634/C2/7> wherein Y is as defined above and W is methyl or ethyl, pharmaceutical compositions thereof and processes for the preparation thereof.  The 1-dehydro compounds obtained by treating 7-methyltestosterone with a 1-dehydrogenating microorganisum, e.g. Septomyxa, may be dehydrated at 9 and 11 positions to form a D 9(11) -compound, which may be treated with hypohalous acid to form a D 1-7-methyl-9a -halo-11b -hydroxytestosterone, which may be treated with a weak base to form a 9b , 11b -epoxy compound, which may be treated with hydrofluoric acid to form a D 1-7-methyl-9a -fluoro-11b -hydroxytestosterone, which may be oxidised with chromic acid to form the corresponding 11-keto compound.  A 17-ester group when present may by hydrolysed to form a free 17-hydroxy compound. 7a -Methyl-19-nortestosterones obtained by treating a 6-dehydro-19-nor-testosterone with a methyl Grignard reagent in the presence of cuprous chloride, may be hydroxylated at 11-position by treatment with a suitable micro-organism and the 11b -hydroxy compound so obtained oxidised with chromic acid at 11 position to obtain an 11-keto compound or at both positions 11 and 17 to obtain an 11,17-diketo compound. The 7-methyl-3,17-dione compound in the form of its 3-enamine may be treated with a Grignard compound, an alkyl or alkenyl lithium compound, or alkali metal alkyne derivative to obtain the corresponding 17-alkylated-7-methyl-19-nortestosterone, the 17-hydroxy group of which may be acylated.  Again hydroxylation followed by oxidation at 11-position may be effected if desired. The 7a -methyl-19-nortestosterones may be dehydrogenated, e.g. with Septomyxa affinis, to yield the corresponding 7a -methylestrones and 7a -methylestradiols. 7a -Methyl-17a -alkynyl-testosterones are obtained by treating the 3-enamine of 7a -methylandrostene-3,17-dione with an alkali metal derivative of an alkyne and hydrolysing the 7a -methyl-17a -alkynyltestosterone 3-enamine so obtained.  Said pharmaceutical compositions, having anabolic, androgenic, anti-estrogenic, gonado-tropic inhibiting, progestational, growth promoting, antifertility and central nervous depressant activity, are employed orally or parenterally as tablets, powders, capsules or pills, solutions, emulsions, suspensions, syrups, or elixirs. Specifications 724,094, 833,183, 853,981 and 863,661 are referred to.