GB674299A - Manufacture of compounds of the androstane series - Google Patents

Abstract

Compounds of the androstane series are manufactured by treating a 3-hydroxy-20-ketopregane with an aromatic per-acid in the absence of an esterifying agent, and either in the absence of an acid catalyst at a temperature below about 30 DEG C. or in the presence of an acid catalyst, and, if desired, subjecting the product to fractional separation or to further oxidation, or both. The starting materials may contain nuclear double bonds (e.g. in the 5 : 6 or 11 : 12 position), these preferably being temporarily protected (e.g. by the addition of halogen or hydrogen halide which are subsequently split off again). Further substituents (e.g. a free or substituted hydroxy or keto group in the 11-position) may also be present. The nature of the products obtained depends on the reaction conditions. In the presence of an acid catalyst (e.g. sulphuric, perchloric or p-toluenesulphonic acid) the per-acid merely oxidizes the -COCH3 group in the 17-position to -OCOCH3, the 3-hydroxy group being, if desired, subsequently oxidized to a keto group (e.g. by means of a metal alcoholate or phenolate and a carbonyl compound, or chromium trioxide or permanganates). In the absence of an acid catalyst, oxidation of the 3-hydroxy group is the main reaction, but some oxidation of the 17-acetyl group occurs as an alternative or concurrent reaction, giving a mixture of three products which may be separated into ketonic and non-ketonic fractions and the former further fractionated by hydrolysis, chromatography and crystallization. In examples: (1) pregnenolone is brominated in carbon tetrachloride, oxidized with monoperphthalic acid in the presence of p-toluenesulphonic acid, and debrominated with zinc dust and glacial acetic acid, producing D 5-androstene - 3b : 17b - diol 17 - monoacetate; (2) the oxidation in (1) is effected with perbenzoic acid in the absence of a catalyst, and progesterone, and testosterone are isolated from the hydrolysis product of the ketonic portion and D 5 - androstene - 3b : 17b - diol 17 - monoacetate from the non-ketonic portion of the reaction product; (3) D 5 : 6-14-allo-17-isopregnene - 3b - ol - 20 - one is brominated and oxidized as in (2), further oxidized with chromium trioxide in glacial acetic acid, and debrominated, giving D 4 : 5-3-keto-17a -acetoxy-14-alloandrostene (which is converted by the action of methanolic caustic potash to 14-allo-17-epitestosterone) and 14-allo-17-isoprogesterone.