GB979037A - New 6-alkyl-steroids - Google Patents

Abstract

The invention comprises steroids of the formula <FORM:0979037/C1/1> (wherein R1 is C1-6 alkyl and R2 is H(OH), H(O acyl) or O) and their preparation by oxidizing a steroid of the formula <FORM:0979037/C1/2> (wherein X is an acyl or a hydrocarbon radical) to the corresponding 5a , 6a -epoxide, treating this with an alkyl magnesium halide to obtain a 3b , 5a -dihydroxy-6b -alkyl-19-nor-pregnane having in the 20-position a hydroxyl or keto group and possibly etherified in the 3-position, oxidizing the 3-hydroxy group, if necessary after acid hydrolysis of the 3-ether group, to give a 3, 20-diketo-5a -hydroxy-6b -alkyl-19-nor-pregnane, and dehydrating and isomerizing this to give the required D 4-3, 20-diketo-6a -alkyl-19-nor-pregnene which, if required, may be reduced to the corresponding 20-ol and esterified. The epoxidation may be effected with an organic peracid or hydrogen peroxide, the oxidation with chromium trioxide, and the dehydration and isomerization with an inorganic or organic acid or with phosphorus oxychloride or thionyl chloride and a tertiary amine, possibly followed by treatment with an acid to isomerize 6b -alkyl compounds to 6a -alkyl compounds. The reduction to a 20-ol may be performed with an alkali metal borohydride, or the D 4-3-keto group may be protected by conversion to a D 3,5-3-enamine, the 20-keto group reduced with an alkali metal aluminium hydride and the 3-enamine group split off. 20b -hydroxy compounds formed predominantly in the reduction can be separated from 20a -hydroxy compounds by chromatography. Examples are given. Steroids of the second general formula above are prepared by enol-acylation of a D 4-3-keto-19-nor-pregnene having a 20-keto, -hydroxy, or -acyloxy group and reduction of the D 3-double bond. The steroids of the invention, which are stated to exercise a progestative, anti-oestrogenic and ovulation-inhibiting effect, may be made up into pharmaceutical compositions with suitable carriers.