Improvements in or relating to 1-substituted-5,10-methylene-19-nor-3-keto-and 3-substituted-5,10-seco-5,19-cyclo-í¸-steroids

摘要

Novel steroids of the formula (wherein X is CN, C1- 8 alkyl, C2- 8 alkenyl or C2- 8 alkynyl; R is C1- 8 alkyl, C2- 8 alkenyl or C2- 8 alkynyl; R1 is H or acyl; R2 is H, C1- 8 alkyl, C2- 8 alkenyl or C2- 8 alkynyl; R3 is H, OH or O-acyl; R4 is H or a - or b -CH3; and Y is H, keto or b -OH) are prepared from the corresponding 5,10-methylene-19-nor-D 1-steroids, in which 17-side chains are protected by ketal formation, and Grignard reagents, the mixture formed being separated by chromatography. On treatment of the 1a -substituted products with a mineral acid in a lower aliphatic alcohol there are produced the corresponding 1a -substituted-D 4-3-keto-steroids. If a 17-keto-starting material is used in the Grignard process a 17a -substituted-17b -ol is obtained. If an alkali metal cyanide replaces the Grignard reagent in the first-described process the 1a -cyano-5, 10-methylene-19-nor-3-keto compounds are produced exclusively, which, by acid treatment as described, give the 1a -cyano-D 4-3-keto-steroids. In this last instance the 20-keto group does not require protection. Protected side chains are hydrolysed by conventional methods. A hydroxyl group may be introduced at C-11 by incubation with adrenal glands or Curvularia lunata. The 11-ols, in which the 21-hydroxy group is protected by acylation, on oxidation give the 11-ones. Hydroxy groups in the products are esterified by conventional methods. 20 - Ethylenedioxy - 5,10 - methylene - 19 - nor-D 1-pregnen -3-one is prepared by oxidizing 20 - ethylenedioxy - D 5 - pregnene - 3b ,19 - diol (prepared by ketalization of the 20-one) to 20 - ethylenedioxy - D 4 - pregnen - 19 - ol - 3 - one and reacting this with 2-chloro-1,1,2-trifluorotriethylamine, another product being 20-ethylenedioxy - 5,10 - seco - 5,19 - cyclo - 10b -fluoro-D 4-pregnen-3-one The corresponding 17a -ol acetates and 16a - and 16b -methyl compounds and the 17a -ol acetates of the last-named are prepared similarly. 16a - Methyl - 17,20;20,21 - bismethylenedioxy-5, 10 - methylene - 19 - nor - D 1 - pregnen - 3 - one is prepared by ketalization of the 17a ,21-diol-20-one.