GB1047709A - 19-halo androstane compounds and process for their production - Google Patents

Abstract

Novel steroids of the formula <FORM:1047709/C2/1> (wherein R is hydrogen or hydrocarbon carboxylic acyl of less than 12 carbon atoms which is optionally substituted; R1 is hydrogen, C1- 8 alkyl, C2- 8 alkenyl or C2- 8 alkynyl; Z is a double bond or a saturated linkage between C-1 and C-2; and X is fluorine or chlorine) are prepared by Oppenauer oxidation of the corresponding D 5-3b -ols, followed, when the D 1,4-compounds are required, by chemical or microbiological dehydrogenation of the thus obtained D 4-3-keto compounds. When R1 is hydroxy, the starting material must be a 17b -acyloxy compound. Saponification of any 17b -acyloxy products gives the corresponding free 17b -ols, which may be re-esterified. 17a -alkynyl products may be hydrogenated to the corresponding 17a -alkenyl compounds. Examples are given, and the conversion of the products to 6a - methyl -, 6a - chloro - and 6a - fluoro - 19 - halo - D 4 - androstene - 17b - ol - 3 - one derivatives via the 3-cycloethylenedioxy - D 5 - androstene compounds and the 3-cycloethylenedioxy-5a , 6a -oxido-androstane derivatives (reaction of the oxido compounds with methyl magnesium bromide leading to 6b -methyl-5a -hydroxy-3-ethylenedioxy compounds which are then treated with acid) and the conversion of these products to the corresponding D 1,4 and D 4,6-compounds are also described. 19 - Halo - 17b - acyloxy - D 5 - androsten - 3b -ols are prepared by converting 19-halo-D 5 -androsten-3b -17-ones into their 3-tetrahydropyranyl ethers, reducing these to the corresponding 17b -ols, converting these to the 17-acylates and hydrolysing off the tetrahydropyranyl group.