GB896817A - Improvements in or relating to steroids and the manufacture thereof - Google Patents

Abstract

The invention comprises compounds having the formula <FORM:0896817/IV (b)/1> wherein R1111 is hydroxy or acyloxy wherein the acyl radical is of a hydrocarbon carboxylic acid containing 1-12 carbon atoms inclusive, R111 is a b -hydroxymethylene or carbonyl group, X1111 is hydrogen, chlorine, bromine or fluorine, R1 is an alkyl or aryl radical and the 1,2-carbon atom linkage represents a single or double bond linkage, compounds having the formula <FORM:0896817/IV (b)/2> wherein R has the same value as R1111, compounds having the formula <FORM:0896817/IV (b)/3> wherein R11 is lower alkyl or aryl and X111 is fluorine chlorine or bromine, and processes for the preparation thereof by dehydrogenating a 6a -alkyl- or aryl-hydrocortisone 21-acylate to produce the corresponding 4,6-pregnadiene II, dehydrating II to obtain a 6-alkyl or aryl-17a ,21-dihydroxy-4,6,9(11)-pregnatriene-3,20-dione 21 ester III, adding hypohalous acid to form the corresponding 9a -halo compound IV, treating IV with a base to obtain a 6-alkyl or aryl-9b ,11b -oxido - 17a ,21 - dihydroxy - 4,6 - pregnadiene - 3,20-dione 21-acylate V, treating V with HF to obtain 6-alkyl or aryl-9a -fluoro-11b ,17a ,21-trihydroxy - 4,6 - pregnadiene - 3, 20 - dione 2I-acylate VI, treating VI with an organic sulphonyl halide to produce a 21-sulphonic acid ester VII and fluorinating VII to obtain a 6-alkyl- or aryl-21 - fluoro - 9a - halo - 11b ,17a - dihydroxy - 4,6 - pregnadiene - 3,20 - dione VIII. The 11-hydroxygroup may be oxidized to an 11-keto group or alternatively the 21-fluoro group may be introduced into an 11-keto compound. A 1,2-double bond may be introduced into either the starting compounds or the products by fermentative dehydrogenation. Examples describe the preparation of 6-dehydro-6-methyl cortisone, 1,6-bis-dehydro-6-methyl cortisone and the corresponding hydrocortisones. Specifications 826,629 and 853,981 are referred to.