Patent GB-886769-A (GB)
Title: Steroid compounds
IPC: C07J5/00
Filed: 1958-07-28
Abstract: Silver dihydrogen phosphate is prepared by reacting monobasic sodium phosphate with silver nitrate in water at 60 DEG -70 DEG C. to give trisilver phosphate, and reacting this with phosphoric acid.  An example is given.  Specifications 805,828 and 862,383 are referred to.ALSO:Steroid phosphates of the formulae <FORM:0886769/IV (b)/1> <FORM:0886769/IV (b)/2> wherein R is keto or hydrogen plus b -hydroxy which may be additionally substituted by one or more of the atoms or groups 2a -methyl, 6a - and 6b -methyl, 9a -halo, 16a -methyl and 16a -hydroxy and which may contain other olefinic links in the nucleus, are separated in solution from inorganic phosphates by contacting the solution with an anion exchange resin or with a water-soluble silver salt to give an insoluble product from which the steroid 21-dihydrogen phosphate solution is then separated. This process may be combined with the additional steps of adding to the resulting solution a compound which forms an insoluble salt with the steroid 21-dihydrogen phosphate and recovering the salt thus formed; acidifying this salt, e.g. with a cation exchange resin, to regenerate the steroid 21-dihydrogen phosphate; and combining this or the steroid 21-hydrogen phosphate which has not been subjected to this additional purification step with an alkali metal alkoxide or hydroxide in an anhydrous organic solvent to give a mono- or di-alkali metal salt of the steroid phosphate. The initial removal of inorganic phosphates may be conducted in an aqueous or an alcoholic solution.  Suitable saltforming reagents for the optional purification step include metallic salts such as zinc salts and amines or amine salts, an extensive list of which is provided. Detailed examples are given, and reference is also made to preliminary treatment of initial steroid phosphate solution, which may additionally contain, as impurities, free 21-hydroxy steroids, 21-iodo steroids, 17a  : 21-oxido steroids, silver salts and phosphoric acid, with a cation exchange resin.  The steroid phosphates of the above formulae are prepared from the corresponding 21-ols, by first reacting these with methane sulphonyl chloride to give the corresponding 21-methanesulphonates, reacting these with alkali metal iodides to give the corresponding 21-iodo compounds, and reacting these with silver dihydrogen phosphate.  The preparation of prednisolone 21-dihydrogen phosphate by this method is described in detail. Specifications 805,828 and 862,383 are referred to.ALSO:Pharmaceutical compositions contain, as essential active ingredients, steroid phosphates of the formulae <FORM:0886769/VI/1> <FORM:0886769/VI/2> (which may be additionally substituted by one or more of the atoms or groups 2a -methyl, 6a -and 6b -methyl, 9a -halo, 16a -methyl and 16a -hydroxy and which may contain other olefinic links in the nucleus) or their alkali metal, zinc or amine salts. Aqueous solutions of the steroid phosphates or their alkali metal salts may be used as ophthalmic preparations or for intravenous injection, while the insoluble zinc and amine salts may be made up into ointments for topical application.  The zinc salts may also be used for oral administration.  Specifications 805,828 and 862,383 are referred to.