GB823940A - Steroid compounds - Google Patents

Abstract

The invention comprises D 1: 4-3,11-diketosteroids of the pregnane series having the general formula <FORM:0823940/IV (b)/1> in which R is a hydrogen atom or an acyl radical, and processes for the preparation of D 1:4-3,11-diketo steroids by treating the corresponding 2,4 - dihalo -, 2 - halo - D 4-, 2,2,4 - trihalo - or 4 - halo - D 1 - 3,11 - diketo - steroids with a dehydrohalogenating agent, particularly a tertiary amine, e.g. collidine, or a nitrogenous carbonyl reagent, e.g. 2,4 - dinitrophenylhydrazine or semicarbazide, followed by hydrolysis, e.g. with pyruvic acid, or in the case of 2,2,4-trihalo steroids, by means of an alkali metal iodide. Preferred D 1: 4-compounds obtainable by the process include D 1: 4 - 3,11,20 - triketo - 17 a -hydroxy - 21 - acyloxy pregnadienes, especially the 21-acetate, propionate and benzoate. In examples: (1) D 1 - 4 - bromo - 3,11,20 - triketo - 17a - hydroxy - 21 - acetoxy - pregnene is refluxed with collidine, the mixture acidified and D 1: 4 - 3,11,20 - triketo - 17a - hydroxy-21-acetoxypregnadiene extracted with chloroform and purified by chromatography on alumina; subsequent hydrolysis in benzene with methanolic KOH gives the free 17,21-diol; (2) 3,11,20 - triketo - 17a - hydroxy - 21 - acetoxyallopregnane (prepared by hydrogenation of cortisone acetate over palladium oxide) is treated with bromine in chloroform yielding 2,4-dibromo - 3,11,20 - triketo - 17a - hydroxy - 21-acetoxyallopregnane, which with 2,4-dinitrophenylhydrazine under nitrogen yields the corresponding 3 - hydrazone of D 1: 4 - 3,11,20-triketo - 17a - hydroxy - 21 - acetoxy - pregnadiene; subsequent warming with pyruvic acid in acetic acid yields the free trione; (3) 3,11,20-triketo - 17a - hydroxy - 21 - acetoxy - allopregnane is brominated in the presence of HBr, yielding 2,2,4-tribromo-allodihydrocortisone acetate, which is refluxed with sodium iodide in acetone and the product refluxed with g - collidine to give D 1: 4 - 3,11,20 - triketo-17a - hydroxy - 21 - acetoxy - pregnadiene; (4) 3,11,20 - triketo - 17a - hydroxy - 21 - acetoxyallopregnane is brominated in chloroform and then dehydrohalogenated using semicarbazide and then pyruvic acid to yield a mixture of D 1 - 3,11,20 - triketo - 17a - hydroxy - 21 - actoxypregnene and the corresponding D 1: 4-pregnadiene, separable by recrystallization; (5) 3,11,20 - triketo - 17a - hydroxy - 21 - acetoxyallopregnane 3 - semi - carbazone is brominated in acetic acid containing a trace of HBr, and the mixture hydrolysed as in (1) to give D 1: 4 - 3,11,20 - triketo - 17a ,21 - dihydroxypregnadiene. D 1 - 4 - Bromo - 3,11,20 - triketo - 17a - hydroxy - 21 - acetoxy pregnane is prepared by brominating 3,11,20 - triketo - 17a - hydroxy-21-acetoxypregnane, separating the 2-bromo derivative from the 4-bromo derivative, refluxing it with collidine and brominating the resulting D 1 - 3,11,20 - triketo - 17a - hydroxy - 21 - acetoxypregnane.