GB1045474A - 8ª‰-methyl-11ª‰-hydroxysteroids and their preparation - Google Patents

Abstract

The invention comprises (1) a process for preparing an 8b -methyl-11b -hydroxy-steroid by lactonizing an 8b -cyano-11b -hydroxy steroid by acid treatment, acylating the carboimidic acid lactone, subjecting the N-acylated lactone to reductive fission, hydrolysing the resulting 8b -iminomethyl-11b -hydroxy-steroid and reducing the resulting 8b -formyl-11b -hydroxysteroid; and (2) 8b -methyl-5a -22-ergostene-3b ,11b -diol and 3,3: 17,17-bisethylenedioxy-8b methyl-5-androsten-11b -ol. The starting material for process (1) may be of the androstane, pregnane, cholane, cholestane, sitostane, ergostane or spirostane series and may contain free or functionally converted hydroxyl and oxo groups and double bonds. The lactonization may be effected with an organic or inorganic acid or a Lewis acid; the acylation with an acid halide or anhydride derived from an alkanoic or aromatic carboxylic acid or alkyl or aryl carbonic acid; the reductive fission by the Birch reduction, which if effected in the presence of a proton source gives the 8-iminomethyl steroid directly or which if effected on an N-alkoxycarbonyl compound in the absence of a proton source gives an N-alkoxycarbonyl dihydro carboimidic acid lactone which is then hydrolysed with an alkali to the required 8-iminomethyl compound; the hydrolysis of the last-named compound by an acid, salt or metal oxide; and the reduction by the WolffKisler method or Huang-Minlon modification thereof. Examples are given. 8b -Cyano-11b -hydroxy-stroids are prepared by treating 9a -halogeno-11-oxo-steroids with a basic agent to give D 8(9)-11-oxo-steroids, treating these with hydrocyanic acid and a trialkyl aluminium to give 8b -cyano-11-oxo-steroids, and reducing these. 3,3:17,17-bisethylenedioxy-11 -keto-5,8-androstadiene, used in this process, is prepared by ketalization of the 3,11,17-trione. 9a - Bromo - 3,11,17 - triketo - 4 - androstene is prepared by oxidation of the 11b -ol.