GB861471A - Improvements in or relating to steroids and the manufacture thereof - Google Patents

Abstract

The invention comprises steroids of the formul\m 9 <FORM:0861471/IV (b)/1> <FORM:0861471/IV (b)/2> and <FORM:0861471/IV (b)/3> (wherein R is hydrogen or the acyl radical of a hydrocarbon mono- or di-carboxylic acid containing 1 to 12 carbon atoms, R1 is alkyl or aryl, R11 is hydroxy or keto and X1 is chlorine, bromine, iodine or fluorine); and their preparation by dehydration e.g. with sulphuric acid or with a hypohalous acid followed by treatment with sulphur dioxide, of a compound of the formula <FORM:0861471/IV (b)/4> (wherein Ac is the above-defined acyl radical), treatment of the resulting 6-alkyl- or 6-aryl-17a : 21 - dihydroxy - 1 : 4 : 9(11) - pregnatriene-3 : 20 - dione 21 - ester with an acid HOX (wherein X is chlorine, bromine or iodine) to obtain the corresponding 9a -halo-11-hydroxy compound, treatment of this with a base e.g. anhydrous potassium acetate, to obtain the corresponding 9b : 11b -oxido compound, reaction of this with HF to obtain the corresponding 9a - fluoro - 11 - hydroxy - compound or the free 21-hydroxy compound and oxidation of this to give the corresponding 11-keto-compound. Compounds of the invention wherein R is a hydrogen atom may be obtained by hydrolysis of any of the above intermediates and may, if desired, be subsequently re-esterified, and compounds of the general formula (I) wherein R11 is keto and X1 is chlorine, bromine or iodine may be obtained by oxidation of the corresponding 11-hydroxy compounds. The oxidations are preferably effected with chromic acid in acetic acid. Other methods of dehydration and epoxidation are also referred to. Examples are given. Steroids of the general formula IV are prepared by reacting 11b : 17a : 21-trihydroxy-5-pregnene - 3 : 20 - dione 3 : 20 - bis - (ethylene ketal) with perbenzoic acid to give 5a : 6a -oxido-11a : 17a : 21 - trihydroxyallopregnane - 3 : 20-dione 3 : 20-bis(ethylene ketal), reacting this with the appropriate alkyl or aryl Grignard reagent R1MgHal to give 5a : 11b : 17a : 21 - tetrahydroxy - 6b - R1 - allopregnane - 3 : 20 - dione 3 : 20 - bis(ethylene ketal), and from this the free 3 : 20-dione, dehydrating this to give 6a - or 6b -R1-hydrocortisone (acetate described), dehydrogenating this with a culture of Septomyxa affinis or other micro-organisms in the absence or presence of steroidal promoters or with selenium dioxide to form 1-dehydro-6a - or 6b -R1-hydrocortisone and, if required, converting this to a 21-ester thereof.ALSO:Pharmaceutical compositions comprise 1-dehydro - 6 - methyl - 9a - fluoro - cortisone and -hydrocortisone and the 21-esters thereof and suitable carriers, and may be in the form of tablets, ointments, lotions, jellies, creams, suppositories, bougies and aqueous suspensions.