Patent GB-902294-A (GB)
Title: Improvements in or relating to steroids and the manufacture thereof
IPC: C07J75/00
Filed: 1959-07-27
Abstract: The invention comprises 6a  - fluoro-16a -methyl steroid compounds having the formula:  <FORM:0902294/IV (b)/1> wherein R111 is hydrogen or the acyl radical of a hydrocarbon carboxylic acid containing 1-12 carbon atoms, R11 is a b -hydroxy or keto group and the 1,2-carbon atom linkage is a single or double linkage, a compound having the formula:  <FORM:0902294/IV (b)/2> wherein R1 is hydrogen or a lower alkyl radical and n is 1 or 2, and R111 is as defined above, a compound having the formula:  <FORM:0902294/IV (b)/3> wherein Ac is the acyl radical of a hydrocarbon carboxylic acid containing from 1-12 atoms and the 1,2 - carbon atom linkage is a single or double bond linkage, a compound having the formula:  <FORM:0902294/IV (b)/4> wherein R1111 is an aryl or alkyl sulphonyl radical, R11 is as defined above, and the 1,2-carbon atom linkage is a single or double bond linkage and processes for the preparation thereof by ketalising 3,11-diketo-16a -methyl-4,17(20)-[cis]-pregnadien - 21 - oic acid lower alkyl ester to form a 3-ketal II, epoxidising II to produce the corresponding 5,6-epoxide III, treating III with hydrogen fluoride to produce a 3-ketalised 3,11-diketo-5a -hydroxy-6b -fluoro-16a -methyl-17(20) -[cis]-allopregnen-21-oic acid lower alkyl ester (V), reducing V to produce a 21-OH group which is esterified to form a 3-ketal of 5a -11b ,21-trihydroxy-6b -fluoro-16a -methyl-17(20) -[cis]-allopregnen-3-one 21-acylate (VII), oxidatively hydroxylating VII to form 3-ketal of 5a ,11b , 21-trihydroxy-6b -fluoro-16a -fluoro-16a -methyl-allopregnane-3, 20-dione 21-acylate VIII, removing the 3-ketal group and dehydrating VIII to produce 6a -fluoro-11b ,17a , 21-trihydroxy-16a -methyl-4-pregnene-3,20-dione 21-acylate IX the ester group of which may be hydrolysed to form IX1, dehydrogenating IX or IX1 to form 6a -fluoro-11b ,17a ,21-trihydroxy-16a -methyl-1,4-pregnadiene-3, 20-dione X or the 21-ester thereof X1, treating IX, IX1, X or X1 with an alkyl or aryl sulphonyl chloride to produce the corresponding 21-sulphonate ester XV, treating XV with sodium iodide to form the 21-iodo compound XVI, treating XVI with silver fluoride to form the 21-fluoro compound XVII. Alternatively the 21-sulphonate may be converted directly into the 21-fluoro compound by treatment with potassium fluoride.  The compounds IX, IX1 and X, X1 may be dehydrated to form the corresponding 9(11)-dehydro compounds or alternatively the 11-OH groups may be oxidised to 11-keto groups.  Illustrative products of the invention are 6a -fluoro-11b ,17a ,21-trihydroxy - 16a  - methyl-4-pregnene-3,20-dione and the 21-acetate thereof, 6a -fluoro-17a ,21-di-hydroxy - 16a  - methyl-4-pregnene-3,11,20-trione and the 21-acetate thereof and the corresponding 1,4-pregnadienes. Specifications 749,201, 761,490, 771,152, 771,344 and 781,712 also are referred to.ALSO:Anti-inflammatory compositions comprise 6a  - fluoro - 11b ,17a ,21 - trihydroxy - 16a  - methyl - 4 - pregnene - 3,20 - dione, 6a  - fluoro - 16a  - methyl - 17a ,21 - dihydroxy - 4 - pregnene-3,11,20 - trione, 6a  - fluoro - 11b ,17a ,21 - tri - hydroxy - 16a  - methyl - 1,4 - pregnadiene - 3,20-dione, 6a  - fluoro - 16a  - methyl - 17a ,21 - di - hydroxy - 1,4 - pregnadiene - 3,11,20 - trione, their 21-esters or 21-desoxy-21-fluoro analogues, and a pharmaceutical diluent.  They are administered as ointments, creams, lotions and sprays together with antibiotics, e.g. penicillins, neomycin, tetracycline, chloramphenicol and novobiocin. Specifications 749,201, 761,490, 771,152, 771,344 and 781,712 also are referred to.