Patent GB-513594-A (GB)
Title: Improvements relating to the production of carbonyl compounds derived from sterols and bile acids or their derivatives
IPC: C07J5/00
Filed: 1938-04-08
Abstract: 513,594. Purifying carbonyl compounds of the sterol series. SOC. OF CHEMICAL INDUSTRY IN BASLE. April 8, 1938, No. 10795. Convention date, May 14, 1937. [Class 2 (iii)] The homologous carbonyl compounds formed by degradation of sterols and bile acids are separated and purified by being subjected to a selective adsorption process, and the adsorbed material recovered from the adsorbate. The preferred method of extraction is that which is known as the method of chromatographic adsorption. Another method of selective adsorption which may be used consists in treating the mixture of carbonyl compounds with an adsorption agent by shaking or stirring to remove easily adsorbed compounds from the solution. The residues may then be further treated by other methods. Alternatively, the mixture of carbonyl compounds may be subjected to a preliminary purification and separation by fractional crystallization before being subjected to the selective adsorption separation. This process may be repeated and also combined with intermediate purification processes, fractional crystallization and sublimation. In the preferred chromatographic method, a solution of the mixture of carbonyl compounds is caused to flow through a column of adsorption agent such as aluminium oxide, the oxides, hydroxides or carbonates of this alkaline earth metals, kaolin, carbon, sugar, or mixtures of any of these. The chromatogram is developed by passing further quantities of the same or a different solvent until the several carbonyl compounds are distributed on different layers, which are best recognized, by their fluorescence in ultraviolet light, when they are elutriated separately. The process of the invention may be applied not only to compounds which contain only carbonyl groups, but also to compounds which contain in addition to carbonyl groups also hydroxyl groups both free and in the form of their derivatives such as ethers, esters, or halides. In examples (1) a benzene solution of the neutral portion obtained by the oxidation of epi-cholestanol acetate by means of chromic acid and subsequent saponification is allowed to flow through a Brockmann adsorption column filled with aluminium oxide. The chromatogram is developed with a 1:1 benzenehexane solution until the first traces of ketone can be recognized in the filtrate. The first portions of the filtrate yield pure epi-cholestanol and the subsequent portions are caused to flow through another column. In the column a zone is formed which is brightly luminous when exposed to ultra-violet light. This zone when separated and elutriated gives pure androsterone. Other portions of the column on working up give epi-allo-pregnandone and epinorcholestanone. Instead of carbonyl compounds containing free hydroxyl groups, carbonyl compounds with esterified hydroxyl groups may be used. (2) The neutral portion obtained by oxidation of cholesterol dibromide acetate is treated with semi-carbazide acetate and the bulk of the dehydroandrosterone acetate semi-carbazone is separated by crystallization. The residue is saponified, and the mixture of ketones so obtained is treated as in example (1) through a column of aluminium oxide, to give layers which on elutriation yield pregnendone, norcholestenone, and trans-dehydroandrosterone. (3) A benzene solution of the neutral portion obtained in the oxidation of cholestenone with chromic acid is treated and worked up as in examples (1) and (2) to give pure androstene-dione and pregnene-dione. In a similar manner the neutral portion of the oxidation products of sitostenone, stigmastenone, chincholenone cholesterol, sitosterol, stigmasterol cinchol or their halogen or halogen hydride addition products may be similarly treated. Saturated compounds such as cholestanone, sitostanone, stigmastanone, and cincholone may also be used as parent materials.