Nouveaux 16alpha -fluoro et 16beta -fluoro-stéroïdes et nouveaux stéroïdes intermédiaires ainsi que leurs procédés de fabrication.

摘要

The invention comprises compounds having the general formula: wherein A represents hydroxyl, - OPO3H2, OSO2R11 wherein R11 is an alkly or aryl radical, or OAcyl the term Acyl representing the acyl radical of an organic carboxylic acid, R1 represents a b -hydroxy or keto group, X represents or , R being attached at the 2-position and representing hydrogen or methyl and Z represents hydrogen, methyl or fluorine provided that when X represents -CH=CH- or -CH2-CH2-, Z represents methyl or fluorine, pharmacologically acceptable water-suloble salts thereof pharmaceutical compositions thereof and a process for the preparation thereof by subjecting a compound having the formula: to oxidative hydroxylation and then, if desired, hydrolysing and/or oxidising to produce the corresponding free 21-hydroxy compound and 11-keto derivative 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-OPO3 H2 compound; treating the 21-OSO2R11 or the 21-iodo compound with a metal fluoride produces the 21-fluoro compounds. Alternatively 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. The oxidative hydroxylation may be effected using osmium tetroxide and an oxidising agent e.g. hydrogen peroxide, an alkyl peroxide or an amine peroxide. The starting compound is obtained by reacting a compound having the formula: wherein Ac,X and Z are as defined above, with selenium dioxide to give a compound of the formula: and converting the latter compound to a compound having the formula: wherein Y is chlorine or bromine, by treatment with thionyl chloride or thionyl bromide, reacting the latter compound with a base in the presence of an inert solvent to produce a compound having the general formula: reacting the latter compound with anhydrous fluoride in the presence of an inert solvent to give a compound having the general formula: and then acylating to produce the corresponding 21-ester. Said compositions having anti-inflammatory properties, are administered in conventional dosage forms such as pills, tablets, capsules, syrups. or elixirs for oral use, or in liquid forms as injectable products, or topically in the forms of ointments, creams or lotions, with or without coacting antibiotics or germicides. Specifications 850,833, 872,112 and 873,219 also are referred to.