GB936806A - Steroid compounds - Google Patents

Abstract

The invention comprises 17a -bromo-9(11)-pregnene compounds of the general formulae <FORM:0936806/IV(a)/1> <FORM:0936806/IV(a)/2> wherein R represents a hydrogen atom or an acyl group, R1 represents a hydrogen or bromine atom, R11 represents a C1-5 alkyl group, and R0 represents a keto or b -hydroxy group; the preparation thereof by contacting the corresponding steroids of the general formulae <FORM:0936806/IV(a)/3> <FORM:0936806/IV(a)/4> wherein R, R11 and R0 have the above significance, with bromine; this process may be extended by dehydrobrominating the resulting bromo substituted steroids to form steroids of the general formulae <FORM:0936806/IV(a)/5> <FORM:0936806/IV(a)/6> wherein R, R11 and R0 have the above significance. The above processes may be modified in that the steroids of the first two formulae above wherein R1 represents hydrogen and R, R11 and R0 have the above significance are prepared by brominating the corresponding 17(20)-unsaturated 20-enol derivatives of the steroids of the second two formulae above, for example, the 20-enol acylates thereof or the 20-zinc, cadmium or magnesium enolates thereof. In the case of the 17a -monobromo-compounds the dehydrobrominating step may be carried out with a tertiary amine such as pyridine, dimethylformamide or lithium chloride in an N,N-dilower-alkylamide. In the case of the 17a ,21-dibromo-compounds, the dehydrobrominating step may be carried out with an alkali metal iodide. 3a -Acetoxy- 11b -hydroxy- 16a -methyl-pregnane is prepared by treating 3a -acetoxy-11,20-diketo-D 16-pregnene with a reagent obtained by reacting cadmium chloride with methyl magnesium bromide in the presence of cuprous chloride and treating the reaction product with hydrochloric acid to form 3a -acetoxy- 11,20-diketo- 16a -methylpregnane, forming the corresponding 20-semicarbazone, reducing the semicarbazone with sodium borohydride to form 3a ,11b -dihydroxy-16a -methyl-20-ketone-pregnane, and acylating this compound. 3a -Acetoxy-16a -methyl- 20-keto-9(11)-pregnene is prepared by brominating 3a ,11b -dihydroxy-20-keto-pregnane or the corresponding 3-acetate in the presence of a strong acid catalyst to form 17a ,21-dibromo-3a -hydroxy-20-keto-9(11)-pregnene or the corresponding 3-acetate, treating this compound with sodium iodide to form 17a -bromo-3a -hydroxy-20-keto-9(11)-pregnene or the corresponding 3-acetate, dehydrobrominating this compound with pyridine to form 3a -hydroxy-20-keto-9(11), 16-pregnadiene or the corresponding 3-acetate, treating the 3a -acetoxy-20-keto-9(11), 16-pregnadiene with a reagent obtained by reacting cadmium chloride and methyl magnesium iodide in the presence of cuprous chloride and decomposing the reaction product. 3a ,20-Diacetoxy-11-keto- 16a -methyl-17(20)-pregnene is prepared by reacting 3a -acetoxy-11,20-diketo-16-pregnene with dimethyl cadmium to form the 20-cadmium enol derivative of 3a -acetoxy-11-keto-16a -methyl-17(20)-pregnene and refluxing this compound with acetic anhydride. 3a ,20- Diacetoxy- 16a -methyl- 9(11),17(20)-pregnadiene is prepared by reacting 3a -acetoxy- 16a -methyl -20-keto-9(11)- pregnene with acetic anhydride in the presence of 2,4-dinitrobenzenesulphonic acid. 20-Cadmium enol derivative of 3a -acetoxy-16a -methyl-9(11),17(20)-pregnadiene is prepared by reacting 3a -acetoxy-20-keto-9(11),16-pregnadiene with the product obtained by reacting cadmium chloride and methyl magnesium iodide in the presence of cuprous chloride.