Verfahren zur Herstellung 6-substituierter 4, 6-Pregnadienderivate

摘要

The invention comprises steroids of the formula (wherein Ac is acyl of 1 to 6 carbon atoms; R is H2, H(BCH3) H(a CH3) or = CH2; R1 and R2 are H or together form a methylene group; R3 is b OH, b O acyl, a O alkyl or b O alkyl, the acyl and alkyl groups having 1 to 6 carbon atoms; and X is chlorine, fluorine or methyl; provided that X is not methyl when R, R1 and R2 are hydrogen and R3 is b OH or b O acyl); the preparation of the steroids wherein R3 is b -OH by reduction of the corresponding ketones with a complex metal hydride, or by hydrolysis of functionally modified 3b -ols; and the preparation of the 3-esters or 3-ethers by acylation or alkylation of the 3b -ols. Etherification may, inter alia, be effected via readily hydrolysable esters, such as tosylates or mesylates, which are then reacted with an alcohol, during which either 3a - or 3b -ethers are produced. Examples are given. 3-Ketones used as starting materials can be prepared by 6-dehydrogenation of 3-keto-4-enes. 16-Methyl derivatives are prepared by hydrogenation of the 16-methylene compounds. 1a ,2a - methylene compounds are prepared by addition of diazomethane to 1-dehydro derivatives followed by fusion of the pyrazoline derivative obtained. 6-Chloro compounds are prepared by reacting 3-enol ethers with N-chloro-succinimide followed by 6-dehydrogenation. 17-Acylates are prepared by standard procedures and, if necessary, can be converted to 17a -ols.ALSO:Pharmaceutical compositions, which are ovulation-inhibitors, comprise steroids of the formula (wherein Ac is acyl of 1 to 6 carbon atoms; R is H2, H(b CH3), H(a CH3) or =CH2;R1 and R2 are H or together form a methylene group; R3 is b OH, b Oacyl, a Oalkyl or b Oalkyl, the alkyl and aryl groups having 1 to 6 carbon atoms; and X is chlorine, fluorine, or methyl; provided that X is not methyl when R, R1 and R2 are hydrogen and R3 is b OH or b Oacyl), and, if desired, oestrogenic steroids such as ethynyloestradiol or its 3-methyl ether or oestradiol esters, e.g. the 3-acetate, in association with suitable carriers. The steroids also have progesterone activity. Solutions, suspensions, emulsions tablets and pills, which may contain preserving, stabilizing or wetting agents, are referred to.