Patent GB-871487-A (GB)
Title: Improvements in or relating to steroid compounds
IPC: C07J75/00
Filed: 1960-02-11
Abstract: The invention comprises steroid compounds of the general formula: <FORM:0871487/IV (b)/1> wherein A represents an alkynyl radical containing less than 7 carbon atoms, R represents hydrogen or the methyl radical, and the lower alkyl radical contains less than 7 carbon atoms.  The compounds may be prepared by oxidising the corresponding 3,17b -diacyloxy-17a alkynyl-3,5-estradienes with manganese dioxide.  In the examples the following are prepared by the above method: 17a -ethynyl (and 1-propynyl, 1-butynyl and 1-hexynyl)-17b acetoxy-4,6-estradien-3-one, 6-methyl-17a ethynyl (and 1-propynyl)-17b -acetoxy-4,6estradien-3-one, and 17a -(1-propynyl)-17b hexanoyloxy-4,6-estradien-3-one and the corresponding 6-methyl compound. 17a -Ethynyl-17b -acetoxy-4,6-estradien-3-one is also prepared by treating 17a -ethynyl-17b -acetoxy-5estren-3-ol with aluminium isopropoxide. 3,17b -Diacyloxy-17a -alkynyl-3,5-estradienes, wherein the acyloxy and alkynyl radicals have the above significance, are prepared by treating the required 17a -alkynyl-19-nor-testosterones with an enolic acylate such as isopropenyl acetate, or with an alkanoic anhydride in the presence of a catalytic amount of a strong acid, e.g. sulphuric acid, an alkanesulphonic such as methanesulphonic, or an arylsulphonic such as benzene- or p-toluenesulphonic, or by treating the required 17a -alkynyl-17b -acyloxy4-estren-3-ones with the required alkanoic acid anhydride in the presence of the above strong acid.  Thus the following compounds may be prepared: 3,17b -diacetoxy,17a ethynyl (and 1-propynyl, 1- butynyl and 1hexynyl)-3,5-estradiene, 3,17b -diacetoxy-6methyl-17a -(1-propynyl)-3,5-estradiene, and 3, 17b -dihexanoyloxy-17a - (1-propynyl)-3,5-estradiene.  17a -Ethynyl-17b -acetoxy-5-estren-3-ol is prepared by reducing 3,17b -diacetoxy-17a ethynyl-3,5-estradiene with sodium borohydride.  17-(1-Butynyl)-19-nor-testosterone is prepared by reacting 3-methoxy-2,5(10)-estradien-17-one with butynyl lithium, and treating the resulting 3-methoxy-17a - (1-butynyl)-2,5(10)- estradien17a -ol with hydrochloric acid. 17-(1-Hexynyl)-19-nor-testosterone is prepared by treating 3-methoxy-2,5(10)-estradien17-one with 1-hexyne in the presence of sodamide, and treating the resulting 17a -(1hexynyl)-3- methoxy-2,5(10)-estradien-17-ol with hydrochloric acid.  6a -Methyl-17a -(1-propynyl)-19-nor-testosterone is prepared by forming 3-ethylenedioxy-19nor-5-androsten-17b -ol from 3b -methoxy-19nor-2,5(10)-androsten-17b -ol or 17b -hydroxy19-nor-4-androsten-3-one and ethylene glycol, acetylating the 3-ethylenedioxy compound, treating the resulting 3-ethylenedioxy-17b acetoxy-19-nor-5(6)-androstene with peroxybenzoic acid to form 3-ethylenedioxy-5a ,6a epoxy-17b -acetoxy-19-nor-androstane, treating this compound with methyl magnesium bromide to form 3-ethylenedioxy-6b -methyl-19-norandrostane-5a ,17b -diol, oxidising this compound with aluminium isopropoxide to form 3-ethylenedioxy-5a - hydroxy-6b - methyl-19nor-androstan-17-one, treating this compound with acetylene gas to form 3-ethylenedioxy6b -methyl- 17a - ethynyl- 19- nor-androstane5a , 17b -diol, treating this compound with ethyl magnesium bromide and then with methyl iodide to form 3-ethylenedioxy-6b -methyl-17a (1-propynyl) -19- nor-androstane- 5a ,17b -diol, and finally treating this compound with hydrochloric acid.  6a -Methyl-17a -ethynyl-19-nor-testosterone is prepared by treating 3-ethylenedioxy-17a ethynyl- 6b -methyl-19-nor-androstone- 5a , 17b diol with glacial acetic acid, and refluxing the resulting 5a ,17b -dihydroxy-17a -ethynyl-6b methyl-19-nor-androstan-3-one with aqueous sodium hydroxide.