7beta-ALKYL-STEROIDS

摘要

1298974 7#-Alkyl steroids UPJOHN CO 13 Aug 1970 [3 Sept 1969] 39095/70 Heading C2U Novel steroids of the formulµ (wherein "alkyl" is C 1-10 alkyl, X is OR in which R is H or C 1-12 hydrocarbon carboxylic acyl, Y1 is C 2-6 alkyl, C 2-6 alkenyl, 3,3,3-trifluoro-1- propenyl, ethynyl, trifluoromethylethynyl or C 3-6 alkylethynyl, Y11 is H, C 1-6 alkyl, C 2-6 alkenyl, 3,3,3-trifluoro-1-propenyl, ethynyl, trifluoromethylethynyl or C 3-6 alkylethynyl, Y is H, C 1-6 alkyl, C 2-6 alkenyl, ethynyl or C 3-6 alkylethynyl, or X and Y, X and Y1 or X and Y11 are oxo, and R1 is H, C 1-6 alkyl, cycloalkyl, tetrahydropyranyl, 5 - hydroxymethyltetrahydropyranyl, 5 - carboxytetrahydropyranyl, tetrahydrofuranyl or C 1-12 hydrocarbon carboxylic aryl) are prepared as follows: (I) are prepared from the corresponding 17#-ols by oxidation to produce the 17-ones followed, when required, by 3-keto protection and conversion of the 17-keto group to a 17α-Y1-17#-OH grouping (where Y1 has all the above values except trifluoropropenyl and trifluoromethylethynyl) with subsequent hydrolysis and, when required, by 17-acylation. The ring-A aromatic compounds are prepared by aromatization of 7#- alkylandrosta - 1,4 - diene - 3,17 - dione to produce 7#-alkyl-estrones which may then be converted to . other required products by standard transformations in the 3- and/or 17- positions. 3-Alkoxy products may then be Birch reduced and the reduction products hydrolysed under mild conditions to give the required #5(10)-3-ones. Before hydrolysis standard transformations in position-17 may be effected, On hydrolysis with a strong acid in an aqueous medium the #5(10)-3-ones are converted to the #4-3-ones (I). Products (I) may also be prepared as follows The 7-alkylation process, effected under known Grignard conditions, gives a mixture of products, (VII) and (VIII). The former can be converted to the latter, and to analogous 17α- substituted compounds, by first acetylating to give the corresponding 19-acetates, preparing the 3-pyrrolidinyl enamines of these, effecting the desired 17-transformations and then hydrolysing the protecting groups. Conversion to (I) is then effected by oxidation to the corresponding 19-oic acids, decarboxylation of these, and hydrolysis of the resulting #5(10)-3-ones. The #5(10)-3-17. diones may be converted to 3-ketals, and these converted to 17α-trifluoromethyl. ethynyl-l7#-ols, which may be reduced to 3,3,3- trifluoro-1-propenyl or 3,3,3-trifluoropropyl products. The novel #4- and #5(10)-steroids are stated to be anti-estrogens with modest androgenic activity, and also to be contraceptive, cholesterol-lowering and antifungal agents. They may be made up into pharmaceutical compositions with suitable carriers.