Patent GB-560812-A (GB)
Title: Manufacture of new compounds of the cyclopentanopolyhydrophenanthrene series
IPC: C07J75/00
Filed: 1942-03-23
Abstract: Compounds of the cyclopentanopolyhydrophenanthrene series unsaturated in ring-C are prepared by treating a compound of the aetiocholane or pregnane series which is unsaturated in the nucleus and which contains as a substituent in ring-C in the 11-position a free or esterified hydroxyl group, with a compound known to be capable of splitting off water or acid.  Parent materials mentioned include compounds which in addition to the substituent in ring-C contain also in the 3-, 7-, 17-, 20-, or 21-position a free or substituted carbonyl hydroxyl or carboxyl group.  Compounds mentioned include D 4.5-11-oxy-pregnene-3 : 20-diones, D 4.5-11 : 21-dioxy-pregnene-3 : 20 - diones, D 4.5-11 : 17 : 21-trioxy-pregnene-2 : 20-diones, D 4.5-11 : 17-dioxy-pregnene-3 : 20-diones, D 4.5-11-oxy-androstene-3 : 17-diones, D 5.6-11-oxy-acetiocholenic acids.  Agents mentioned for splitting off a hydroxyl group in the 11-position include a mineral acid preferably in a solvent such as acetic acid, alcohol, or dioxane, phosphorus oxychloride, a bisulphate, formic acid or oxalic acid, an acid anhydride such as acetic anhydride or phosphorus pentoxide, a catalyst such as an iodide or a carboxylic acid salt. An esterified hydroxyl group can be split off by the above agents and also in addition by means of alkalis, alkaline earths, carbonates, carboxylic acid salts, or organic bases such as pyridine or dimethylaniline.  A raised temperature, and/or reduced pressure may also be used.  The compounds produced by the invention may be esterified or etherified if desired, and also hydroxyl groups may be oxidized to keto groups, or alternatively keto groups present may be reduced to hydroxyl groups.  In examples: (1) D 4.5-11 : 21-dioxypregnene-3 : 20-dione-21-acetate is refluxed with an acetic acid solution of glacial acetic acid, and then treated with acetic anhydride and pyridine.  On separating the reaction products by chromatographic analysis there are obtained two compounds both of empirical formula C23H30O4.  Probable constitutions are indicated for these compounds which act in the manner of hormones of the suprarenal cortex.  Two further products can also be obtained which are of unknown constitution.  Alternative starting materials mentioned for the process of this example include D 5.6-3-oxy-21-acyloxy compounds and also D 4.5-11-epi-21-dioxy-pregnene-3 : 20-dione-diacetate.  (2) D 4.5-11-oxypregnene-3 : 20 dione is boiled under reflux with a glacial acetic acid solution of sulphuric acid to give two products of empirical formula C21H28O2 which are separated by chromatographic analysis.  The same product is obtained when the corresponding enol acetate is used instead of D 4.5-11-oxy-pregnene-3 : 20 dione.  The same result is also obtained by splitting off water from D 5.6-3 : 11-dioxy-pregnene-20-one, and subsequent oxidation with chromic acid. Similarly there may be obtained from D 5.6-3-oxy-, or acyloxy-, or D 4.5-3-keto-11-oxy-etioallo-cholenic acid the corresponding D 4.5; 8.9-, and D 4.5; 9.11- diene acids.  (3) D 4.5-11-oxyandrostene-3 : 17-dione is refluxed with a glacial acetic acid solution of concentrated hydrochloric acid to give two products of the empirical formula C19H22O2 which are probably D 4.5; 9.11-, and D 4.5; \ 8.9-androstadiene-3 : 17-dione.