Patent GB-898293-A (GB)
Title: Improvements in or relating to steroids and the manufacture thereof
IPC: C07J7/00
Filed: 1960-03-14
Abstract: The invention comprises compounds of the formula <FORM:0898293/IV (b)/1> wherein R11 is an aryl or alkyl sulphonyl radical, R111 is a hydrogen or the acyl radical of a hydrocarbon carboxylic acid containing 1-12 carbon atoms, Y is b -hydroxymethylene or carbonyl, X11 is hydrogen, fluorine or chlorine, X111 is bromine or iodine and Ac is the acyl radical of a hydrocarbon carboxylic acid containing 1-12 carbon atoms, and processes for the preparation thereof by ketalising 3, 11-diketo - 16b  - methyl - 4, 17 (20) - [cis]-pregnadien-21-oic acid lower alkyl ester I, epoxidising the 3-ketal II to produce a 5,6-epoxide III, treating III with HF to obtain a 3-ketalised 3,11-diketo-5a -hydroxy-6b -fluoro-16b -methyl - 17 (20) - [cis] - allopregnen - 21 - oic acid lower alkyl ester V, reducing V, e.g. with LiAlH4, to obtain a 3-ketal of 5a ,11b ,21-trihydroxy - 6b  - fluoro - 16b  - methyl - 17 (20) - [cis]-allopregnen-3-one VI, esterifying VI at 21-position and oxidatively hydroxylating to obtain a 3 - ketal of 5a , 11b , 17a , 21 - tetrahydroxy - 6b  - fluoro - 16b  - methylallopregnane - 3, 20 - dione 21-acylate VIII, treating VIII with a mineral acid to obtain 6a -fluoro-11b ,17a ,21-trihydroxy - 16b  - methyl - 4 - pregnene - 3, 20 - dione 21-acylate IX; IX or the corresponding free 21-hydroxy compound may be dehydrogenated to obtain 6a -fluoro-11b ,17a ,21-trihydroxy-16b  - methyl - 1,4- pregnadiene - 3, 20 - dione X, or its 21-acylate XI; XI is dehydrated to produce 6a  - fluoro - 16b  - methyl - 17a , 21 - dihydroxy - 1, 4, 9 (11) - pregnatriene - 3, 20 - dione 21 - acylate XIII; XIII is treated with hypohalous acid to give 6a -fluoro-9a -halo-11b ,17a ,21-trihydroxy - 16b  - methyl - 1, 4 - pregnadiene - 3,20-dione 21-acylate XIV; XIV is treated with a base to obtain a 9(11)-oxido compound XV; XV is treated with HF to obtain 6a -9a -difluoro-11b , 17a , 21 - trihydroxy - 16b  - methyl - 1, 4 - pregnadiene-3,20-dione 21-acylate XVI.  The 21-hydroxy group in any of the aforesaid compounds may be converted into a 21-fluoro substituent by treatment with an alkyl or aryl sulphonyl chloride to obtain the corresponding 21-sulphonate, which is converted into a 21-iodo compound with sodium iodide and then treated with silver-fluoride.  The 11b -hydroxy groups may be oxidised to 11-keto groups with CrO3.  Illustrative products of the invention are 6a  - fluoro - 11b , 17a , 21 - trihydroxy - 16b  - methyl - 4 - pregnene - 3, 20 - dione, 6a  - fluoro - 16b  - methyl - 17a , 21 - dihydroxy - 4 - pregnene - 3,11,20-trione, the 21-acetates thereof, 6a ,9a -difluoro - 11b , 17a , 21 - trihydroxy - 16b  - methyl - 4-pregnene-3,20-dione and the corresponding 1,4-pregnadienes. Specifications 749,201, 771,344, 781,712 and 898,294 are referred to.ALSO:Pharmaceutical compositions comprise a compound having the formula <FORM:0898293/VI/1> wherein Ac is the acyl radical of a hydrocarbon carboxylic acid having 1-12 carbon atoms X111 is hydrogen or halogen, Y is b -hydroxymethylene or carbonyl and the dotted line represents a single or double bond linkage, or the corresponding free hydroxy compounds, and a pharmaceutical diluent.  They are employed in ointments, tablets and sterile suspensions with or without coacting antibiotics, e.g. penicillins, neomycin, tetracycline, chloramphenicol, and novobiocin.  Specifications 749,201, 771,344, 781,712 and 898,294 are referred to.