17ª‰-hydroxy-17ª‡-alkynyl steroids of the 19-norandrostane class and method for their preparation

The invention comprises pure crystalline 17 a - (prop - 1 - ynyl) - 17b - hydroxy - 19 - norandrost - 4 - en - 3 - one of m.p. 165 to 167 DEG C. and [a ]22D-37 DEG (c,0,19 in chloroform); pure crystalline 17 a -(hex-1-ynyl)-17b -hydroxy-19-norandrost-4-en-3-one of m.p. 134 to 136 DEG C. and [a ]20D-40 DEG (c,0,62 in chloroform); 17 a -(but-1-ynyl)-17b -hydroxy-19-norandrost-4-en-3-one; 17 a -(pent-1-ynyl)-17b -hydroxy-19-norandrost - 4 - ene - 3 - one; and the preparation of 19-norandrostenes of the general formula: where R is an alkyl group of at most 4 carbon atoms) by reacting a 17-oxo-steroid having a protected oxo group at the 3-position with the appropriate alkynyl magnesium halide and subsequently regenerating the desired steroid from the complex so formed. Conveniently a solution of the 17-oxo-steroid in a solvent such as tetrahydrofuran is added to an excess of an alkynyl magnesium bromide or iodide in a similar solvent and the mixture refluxed or allowed to stand at room temperature for several hours. Thereafter, the complex may be decomposed by addition of, for example, aqueous oxalic acid or ammonium chloride and the product isolated with ether. The oxo group at C3 may be protected, for example, by ketal or enol ether formation, and subsequently regenerated. In examples (1) to (4) 3-ethoxy-19-norandrosta-3:5-dien-17-one is reacted with 1-propyne, 1-butyne, 1-pentyne and 1-hexyne respectively in presence of magnesium and ethyl bromide (or 3-methoxy-19-norandrost-2:5(10) -dien-17-one can replace the 3:5-dien in (1)) to give the compounds of the invention. Specification 789,066 is referred to.ALSO:Pharmaceutical preparations comprise compounds of the formula: (wherein R is an alkyl group containing at most 4 carbon atoms) in admixture with a solid or liquid carrier. They may take the form of tablets, cachetes, capsules, tablets for sublingual absorption, elixirs or suppositories. Examples disclose tablets containing 17a -(prop-1-ynyl)-17b -hydroxy-19-nor androst-4-ene-3-one and, separately, the corresponding but-1-ynyl and pent-1-ynyl compounds. Specification 789,066 also is referred to.