| 摘要 |
The invention comprises compounds of the formula <FORM:0894604/IV (b)/1> wherein X111 is a halogen or a hydrogen atom, R2 is a b -hydroxy or a keto group, X11 is a chlorine, fluorine or hydrogen atom, Ac is the acyl radical of a hydrocarbon carboxylic acid containing 1-12 carbon atoms, and R1 is the sulphonyl radical of a hydrocarbon sulphonic acid containing 1-12 carbon atoms, and 21-esters of the 21-OH compounds with hydrocarbon carboxylic acids containing from 1-12 carbon atoms, and processes for the preparation thereof by treating 6a -methyl-11b ,21-dihydroxy-4,17(20)cis-pregnadiene-3-one, with a dialkyl oxalate, perchloryl fluoride and then a base to obtain 2 - fluoro - 6 a - methyl - 11b , 21 - di - hydroxy - 4, 17 (20) - pregnadiene - 3 - one IV, oxidatively hydroxylating IV to obtain 2-fluoro-6a - methyl - 11b , 17a , 21 - trihydroxy - 4 - pregnene-3,20-dione 21-acylate VI, oxidising VI to obtain 2-fluoro-6a -methyl-17a ,21-dihydroxy-4-pregnene-3,11,20-trione VII or alternatively dehydrating VI to obtain 2-fluoro-6a -methyl- 17a , 21a - dihydroxy 4, 9 (11) - pregnadiene - 3, 20 - dione 21-acylate VIII, treating VIII with hypohalous acid to form 2 - fluoro - 6a - methyl - 9a - halo - 11b , 17-, 21 - trihydroxy - 4 - pregnene - 3, 20 - dione 21-acylate IX, treating IX with a base to form 2 - fluoro - 6a - methyl - 9b , 11b - epoxy - 17a , 21 - dihydroxy - 4 - pregnene - 3, 20 - dione 21-acylate X, and treating X with HF to obtain 2, 9a - difluoro - 6a - methyl - 11b , 17a , 21 - tri - hydroxy - 4 - pregnene - 3, 20 - dione 21 - acylate. The 11-hydroxy group may be oxidised to 11-keto with chromic acid. A 21-fluoro substituent may be introduced by treating the 21-OH compound with an organic sulphonyl halide to produce a 21-sulphonate ester which is treated with sodium iodide to produce a 21-iodo compound which is reacted with silver fluoride. Alternatively, the 21-sulphonate ester is reacted directly with an alkali metal fluoride. Detailed examples are given. Specifications 771,344 and 781,712 are referred to.ALSO:Anti - inflammatory compositions comprise compounds of the formul <FORM:0894604/VI/1> wherein X111 is halogen or a hydrogen atom, R2 is b -hydroxy or keto, X11 is a chlorine, fluorine or hydrogen atom and 21-esters of the 21-OH compounds with hydrocarbon carboxylic acids containing from 1-12 carbon atoms with coacting antibiotics, e.g. neomycin sulphate, novobiocin, bacitracin, circulin, polymyxin B sulphate, gramicidin, streptomycin sulphate, dihydrostreptomycin sulphate, oxytetracycline, chlortetracycline, tetracycline and chloramphenicol, or the sulphonamides and a pharmaceutical carrier. They are employed orally, parenterally or topically as tablets, ointments, lotions, jellies, creams, suppositories or aqueous suspensions. Specifications 771,344 and 781,712 are referred to. |
