Patent GB-946576-A (GB)
Title: Improvements in or relating to steroids
IPC: C07J5/00
Filed: 1960-12-19
Abstract: The invention comprises a compound having the formula: <FORM:0946576/C2/1> wherein A represents hydroxyl, -OPO3H2, -OSO2R11 wherein R11 is an alkyl or aryl radical, or O Acyl the term acyl representing the acyl radical of an organic carboxylic acid.  R1 represents a b -hydroxy or keto group, X represents <FORM:0946576/C2/2> or <FORM:0946576/C2/3> , R being attached at the 2-position and representing hydrogen or methyl, Z represents hydrogen methyl or fluorine and Hal represents chlorine, fluorine, bromine or iodine provided that 1/. when A represents OPO3H2 or OSO2R11 Hal represents fluorine and 2/. when X represents -CH=CH-, Z represents methyl or fluorine and processes for the preparation thereof by dehydrating a compound having the formula: <FORM:0946576/C2/4> wherein Ac, X, and Z are as above defined, hypohalogenating to form the corresponding 9a -chloro,bromo or iodo derivative and then if desired epoxidising to produce a compound having the general formula: <FORM:0946576/C2/5> wherein Ac, X and Z are as above defined, and then reacting this latter compound with aqueous hydrogen fluoride or aqueous hydrogen chloride to form the corresponding 9a -fluoro- or 9a -chloro derivative and then if desired oxidising or hydrolysing to produce the corresponding 11-keto 21-ester or free 21-hydroxy compound; subsequently the 21-hydroxy compound may be treated with an alkyl or aryl sulphonyl halide to obtain a 21-OSO2R11 compound which may be treated with an alkali metal iodide to obtain a 21-iodo compound or silver dihydrogen phosphate to obtain a 21-OPO3H2 compound; treating the 21-OSO2 R11 or the 21-iodo compound with a metal fluoride produces the 21-fluoro compounds.  In the process above the dehydration step may be effected with N-bromacetamide and anhydrous sulphur dioxide, the hypohalogenation step with perchloric acid and N-bromoacetamide or N-iodo-succinimide, the epoxidation step with anhydrous potassium acetate and the oxidation step with chromic acid.  In an alternative process the 21-phosphate is obtained by treating the 21-sulphonate with phosphoric acid in the presence of a tertiary amine and then acidifying the 21-hydrogen phosphate so produced to obtain the free 21-phosphate compound.  Specifications 850,833, 872,112, 873,219, 946,578 and 946,579 are referred to.ALSO:Pharmaceutic compositions having anti-inflammatory activity and containing a compound of the formula:  <FORM:0946576/A5-A6/1> wherein A represents -OH, -OPO3H2, -OSO2R11 wherein R11 is an alkyl or aryl radical (1-10 carbon atoms) or -OAc, the term Ac representing the acyl radical of an organic carboxylic acid particularly a hydrocarbon carboxylic acid having 1-12 carbon atoms, R1 represents b -OH or Keto, X represents <FORM:0946576/A5-A6/2> or <FORM:0946576/A5-A6/3> , R being attached at the 2-position and representing H or CH3, 2 represents H, CH3, or F and Hal represents halogen provided that: (1) when A represents -OPO3H2 or -OSO2R11 Hal represents fluorine; and (2) when X represents -CH = CH-, Z represents CH3 or F, and a coacting antibiotic, are administered orally as pills, tablets, capsules, syrups or elixirs, in liquid forms for injectable products, or topically as ointments, creams or lotions. Specifications 850,833, 872,112, 873,219, 946,578 and 946,579 are referred to.