GB1041277A - 13-alkyl steroids related to oestradiol - Google Patents

Abstract

Novel steroids of the general formula <FORM:1041277/C2/1> wherein the lines connecting R1, R2, OH and H to the steroid nucleus have no configurational significance, RO represents a hydroxy, alkoxy or acyloxy group, R1 represents an alkyl group having at least 2 carbon atoms, R2 represents an unsubstituted or substituted alkyl, alkenyl or alkynyl group (a suitable substituent is methoxy) trans to R1, ring C is saturated or contains an ethylenic bond terminating at the 9-position, C:D ring junction is in the trans configuration, any hydrogen at the 8-position is anti to the hydrogen at the 14-position and any hydrogen at the 9-position is trans to that at the 8-position, are prepared by reacting the corresponding 17-keto-steroids with an organo-metallic reagent providing the group R2 and, if necessary, esterifying (or etherifying) a 3-hydroxy group contained in the product; by reducing steroids of the above general formula having an unsaturated C ring and R2 representing unsubstituted alkyl with alkali metal in liquid ammonia to form the corresponding compounds in which the C ring is saturated; or by reducing steroids of the above general formula having 9(11)-unsaturation and R2 has the above significance by catalytic hydrogenation in which case any unsaturated R2 group becomes saturated; or by selectively reducing steroids of the above general formula wherein R2 represents an unsubstituted alkenyl or alkynyl group to form the corresponding steroids wherein R2 represents an unsubstituted alkyl or alkenyl group by selective catalytic hydrogenation; or by isomerizing steroids of the above general formula having 8(9)-unsaturation to the corresponding steroids having 9(11)-unsaturation with acid. The above processes may be modified in that a 13b - alkyl - 17a - ethynyl - 18 - nor - oestradiol reactant is prepared by oxidizing a corresponding 13b -alkyl-18-nor-oestradiol to the corresponding 17-keto compound, etherifying this compound to give the corresponding 3-substituted or unsubstituted alkyl ether-17-keto compound, and ethynylating the ether with an ethynylmagnesium halide. By "alkoxy" is meant the alcoholate radical derived from an alcohol such as an alkyl alcohol where the alkyl group may be substituted by a methoxy or hydroxy group. Examples of alkoxy and acyloxy groups which may be present at the 3-position in the first general formula above are methoxy, ethoxy, methoxymethoxy, hydroxyethoxy, glyceryloxy, benzyloxy, acetoxy and benzoyloxy groups. Suitable organo-metallic reagents are Grignard reagents, lithium alkyls and lithium, sodium and potassium acetylides and carbides. The above formula includes all states of resolution except the resolved 13a -enantiomer.