GB973146A - 9-halogenated 18:11-lactones of 11ª‰-hydroxy-pregnane-18-acids - Google Patents

Abstract

The invention comprises 18, 11-lactones of 11b -hydroxy-9a - X- 20- R1-21-R2-pregnane-18-acids in which X is a fluorine, chlorine or bromine, R1 is a free or ketalized oxo group, or a hydrogen atom and a free or esterified hydroxyl group, and R2 is a hydrogen atom or a free, esterified or etherified hydroxyl group, and particularly steroids of this class having the formula <FORM:0973146/C1/1> and the corresponding D 5-3-ketals, and the 19-nor analogues of all these steroids. They may be prepared by treating the 18, 20b -lactones of D 4-3-oxo-9, 11b - oxido-20b -hydroxy-pregnene 18-acids with a hydrohalic acid and then translactonizing the resulting 18, 20-lactones of 9a -halogen-11b -hydroxy-pregnene-18-acids. The 9a -bromo compounds can also be prepared by direct additive combination of hypobromous acid with the 18, 20-lactone of D 4,9(11)-3-oxo-20b -hydroxy-pregnadiene-18-acid Oxidation of the so-formed 20-hydroxy compounds gives the 20-ketones, while treatment with, for example, ethylene glycol and p-toluenesulphonic acid gives the corresponding D 5-3-ethylenedioxy compounds, which may also be oxidized to the 20-ketones. The D 5-3-ketals may be further processed by oxalic ester condensation, iodination and cleavage with sodium acetate into the 18, 11-lactones of D 5-3-ethylenedioxy-9a -halo-11b -hydroxy -20 - oxo - 21 - acetoxy - pregnene-18-acids which on treatment with aqueous perchloric acid in tetrahydrofuran yield the 18, 11-lactones of D 4-3, 20-dioxo-11b , 21-dihydroxy-9a -halo-pregnene -18-acids. By ketalization, reduction with lithium aluminium hydride and ketal cleavage these may be converted to 9a -halo-aldosterones. Detailed examples of all these processes are given. Specifications 973,143, 973,144 and 973,145 are referred to.