4-OXA-ANDROSTANES AND A PROCESS FOR THE MANUFACTURE THEREOF

摘要

1,247,021. 4-Oxa-steroids. F. HOFFMANNLA ROCHE & CO. A.G. 1 Nov., 1968 [3 Nov., 1967], No. 51937/68. Heading C2C. The invention comprises compounds of formula wherein R1 is H, C 1-7 alkyl or C 1-7 alkanoyl, R2 is H or C 1-7 alkyl, A is Cl 2 , Br 2 or (X, H), where X is Cl, Br or F and may be in theα- or #-configuration, and the broken line in the 1,2-position denotes an optional bond. The #1-compounds are prepared by dehydrogenation of the 1,2- saturated compounds, and the latter are prepared (a) by acid cyclization of compounds of formula which, when prepared by reducing the corresponding 5-ones or A6-5-ones, need not be isolated; or (b) from compounds of formula either directly by treatment with a halogen, or by conversion with peracids to 5α,6α-epoxy compounds and treatment of the latter with a hydrogen halide. Compounds of Formula I are interconvertible: (i) by conversion of a 17- hydroxy or 17-alkoxy compound into a 17- alkanoyloxy compound; (ii) by conversion of a 6#-halo compound into a 6α-halo compound using bromide ions; and (iii) by conversion of 5#-compounds into 5α-compounds by hydrolysis of the former to 5-hydroxy-3,5-seco-A- norandrostan-3-oic acids which are oxidized to the corresponding 5-oxo compounds, and reduction and lactonization of the latter. 17# - Hydroxy - 17α- methyl - 3,5 - seco - A- nor - androst - 5 - en - 3 - oic acid is prepared by the successive actions of Zn and KOH on 6α- bromo - 17# - hydroxy - 17α- methyl - 4- oxa-5#-androstan-3-one. Compounds of Formula II and their aforesaid 5-oxo antecedents comprise the subject-matter of Specification 1,247,021. Antiandrogenic compositions for oral, parenteral and topical administration comprise a compound of formula wherein A is Cl 2 , Br 2 or (α-X, #-H) and R1, R2, X and the broken line are as defined above, and a carrier.