GB884412A - New 6-methyl-19-nor-steroids and process for the preparation thereof - Google Patents

Abstract

The invention comprises steroids of the formula <FORM:0884412/IV (b)/1> (wherein Z is H(b OH), H(b OAcyl, R(b OH), R(b OAcyl) or = O in which R is a saturated or unsaturated aliphatic hydrocarbon radical of at most 4 carbon atoms) and the preparation thereof by oxidizing a d 5-3 : 17-dihydroxy-19-nor-androstene-3-mono-acylate or -3 : 17-diacylate to the corresponding 5a : 6a -oxido-compound, preferably with a peracid, reacting the product with a methyl metal compound, preferably a methyl magnesium halide, to obtain 3b : 5a : 17b -trihydroxy-6-methyl-19-nor-androstane, treating this with an oxidizing agent, e.g. chromium trioxide to obtain the corresponding 3 : 17-diketone, treating this with a dehydrating agent, e.g. an inorganic acid in alcohol, to obtain the compounds of the above general formula, wherein Z is a keto group, and then, if desired, converting the 17-keto group into another group Z as defined above by known methods. Such methods include (1) reduction, e.g. with a complex metal hydride, to a 17b -hydroxy group, during which process the D 4-3-keto group must be protected, for example by conversion to a 3-enol ether or a 3-enamine and released again after the reduction, for example with the use of an organic or inorganic acid; (2) concomitant alkylation and reduction to a 17b -hydroxy-17a -alkyl grouping, for example by means of a metal derivative of a saturated or unsaturated hydrocarbon such as a Grignard reagent, during which process the 3-keto group must be protected, e.g. by conversion to an enolester or enolether, and subsequently released, for example by treatment with an acid; (3) treatment with an alkyne in the presence of an alkali (including alkaline earth) metal or alkali metal compound, to give the 17b -hydroxy-17a -alkynyl compounds; (4) reduction of the products of (3) to the corresponding alkenyl or alkyl compounds; and (5) esterification of the 17b -hydroxy compounds to the 17b -acyloxy compounds, for example by means of the appropriate acid or an anhydride or halide thereof. Examples are given and an extensive list of suitable esterifying acids is provided. The preparation of D 4-3-keto-6-methyl-17b - hydroxy - 17a - methyl - 19 - nor - androstene by oxidising the 3 : 17 - diacetate of D 5-3b : 17b -dihydroxy - 17a - methyl - 19 - nor - androstene (obtained from the diol and acetic anhydride) to 3b : 17b -diacetoxy-5a : 6a -oxido-17a methyl-19-nor-androstane, reacting this with methyl magnesium bromide to form 3b - 5a : 17b -trihydroxy-6-methyl-17a -methyl-19-nor-androstane, oxidizing this to 3-keto-5a : 17b -dihydroxy-6-methyl-17a -methyl-19-nor-androstane and dehydrating this, also is described, and the preparation of other 17a -hydrocarbon compounds by a similar method also is referred to. D 5-3 : 17-Dihydroxy-17a -alkyl-19-nor-androstenes, are prepared by converting 17a -alkyl-19-nor-testosterones into 3-enol acylates thereof and reducing the 3 : 4-double bond.