GB1169739A - A-Nor-Steroids - Google Patents

Abstract

1,169,739. A-nor-steroids. MERCK & CO. Inc. 20 Oct., 1966 [21 Oct., 1965; 11 July, 1966], No. 46943/66. Headings C2C and C2U. Novel compounds of the formula (wherein R 1 is H or CH 3 ; R 3 is a C 2-4 aliphatic hydrocarbon radical; Q is methylene substituted by OH and by a group Z, Z being an alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, phenyl or benzyl radical; and one of X and Y is methylene and the other is methylene substituted by OH and by one of the Z values) which may contain nuclear halogen and/or alkyl substituents are prepared from the corresponding 10 - R 1 - 13 - R3 - 17 - hydroxy - A - nor - 5α - gonan - 2 - ones (I). These on reaction with an organo metallic ketone additive agent such as a Grignard reagent, a lithium alkyl or an organometallic alkyne or halo-alkyne give the corresponding 2-substituted-2,17-dihydroxy- A-nor-5α-gonanes; oxidation of the 17-hydroxy group gives the 17-ketones which may then be similarly reacted to give the 2,17-disubstituted - 2,17 - dihydroxy - A - nor - 5α- gonanes (it is preferred that the 2-hydroxy group be protected, e.g. as a tetrahydropyranyl ether, before the second reaction with an organometallic compound). If the substituents in the 2- and 17-positions are to be the same a 10-R 1 - 13 - R 3 - A - nor - 5α - gonane - 2,17 - dione may be reacted with 2 moles of the appropriate organo-metallic compound. Compounds having the substituents on the 16-carbon atom instead of the 17-carbon atom are prepared from 2- hydroxy - A - nor - 5α - gonan - 16 - ones by similar processes. Other conventional oxidation, reduction and substitution procedures provide other compounds of the invention. Products wherein Z is alkynyl or haloalkynyl may be reduced with hydrogen in the presence of a Lindlar catalyst to the corresponding alkenyl compounds or with hydrogen in the presence of a noble metal catalyst to the corresponding alkyl or haloalkyl compounds. 10 - R 1 .13 - R 3 - 2 - hydroxy - A - nor - 5α- gonan-16-ones are prepared from compounds (I) by 2-ketalization, 17-oxidation, reaction of the 17-keto compounds with isoamyl nitrite and a base to give the 16-oximino derivatives, treatment with an acidic reducing agent to provide the corresponding 17-hydroxy-A-nor- 5α-gonane-2,16-diones, esterification of the 17-OH group with a sulphonyl chloride and reduction with a mild reducing agent. Compounds (I) are prepared by the process In the third stage, which is an oxidation with e.g. CrO 3 , a mixture of the 2,3-seco- and 3,4- seco-dioic acids is produced, but only the former is shown. Ac is an acyl group. The A-nor-steroids of the invention, which are stated to be useful in the control of the estrus cycle in mammals, may be made up into pharmaceutical compositions with suitable carriers.