Patent GB-1026501-A (GB)
Title: Improvements in or relating to steroids and the manufacture thereof
IPC: C07J13/00
Filed: 1962-10-12
Abstract: The invention comprises 16a -chloro steriods of the structural formula <FORM:1026501/C2/1> wherein R is hydroxyl, OAcyl or -OPO3H, the term Acyl representing the acyl radical of a hydrocarbon carboxylic acid containing from 1-12 carbon atoms, inclusive, R1 is an alkyl or aryl organic sulphonyl radical, X is hydrogen or fluorine, X1 is bromine or chlorine, Y is hydrogen, methyl or fluorine and processes for the preparation thereof by oxidatively hydroxylating an 11b -hydroxy-16a -chloro-21-acyloxy-1,4,17 (20-pregnatriene-3-one to produce 11b , 17a ,21-trihydroxy-16a -chloro-1,4-pregnadiene-3,20-dione 21-acylate III, dehydrating III with an N-haloacylamide and sulphur dioxide to form a 17a ,21-dihydroxy-16a -chloro-1,4,9(11)-pregnatriene-3,20 -dione 21-acylate IV, treating IV with an N-haloacylamide to form the corresponding 11b ,17a ,21 - trihydroxy - 9a  - chloro-, bromo- or iodo-16a -chloro-1,4-pregnadiene-3,20-dione 21-acylate V; treating V with a mild base such as sodium acetate to form a 9b ,11b -oxido-17a ,21 -dihydroxy-16a -chloro-1,4-pregnadiene-3,20-dione 21-acylate VI, and treating VI with HF to form a 9a -fluoro-11b ,17a ,21-trihydroxy-16a  - chloro - 1,4 - pregnadiene - 3,20 - dione 21-acylate. The oxidative hydroxylation may be effected with osmium tetroxide and an organic peroxide or an aryliodoso acetate.  The 21-hydroxy compounds so obtained may be converted into the corresponding 21-sulphonyloxy compounds by means of an organic sulphonyl halide, which on further treatment with sodium or potassium iodide yield the corresponding 21-iodo compound.  The 21-iodo compounds on treatment with silver dihydrogen phosphate gives 16a  - chloro - 11b ,17a ,21 - trihydroxy - 1,4- pregnadiene - 3,20 - dione - 21 - dihydrogen phosphate which may be esterified in 17-position, or with silver fluoride 16a -chloro-21-fluoro-11b , 17a -dihydroxy-1,4-pregnadiene-3,20-dione is obtained.ALSO:Pharmaceutical compositions having anti-inflammatory and glucocorticoid activity and containing compounds having the formula <FORM:1026501/A5-A6/1> (wherein R is hydroxyl, O Acyl or OPO3H2, the term acyl representing the acyl radical of an organic carboxylic acid having 1-12 carbon atoms inclusive; X is hydrogen or fluorine and Y is hydrogen methyl or fluorine) are administered orally in pills, tablets, capsules, syrups elixirs, powders and granules, parenterally in sterile liquid form or topically in the forms of ointments, creams and lotions with or without coacting antibiotics e.g. chloramphenicol, penicillin, tetracyclines, erythromycin, novobiocin, polymyxin and bacitracin; analgesics e.g. aspirin, sodium salicylate, N-acetyl-p-aminophenol and salicylamide; amphetamines and tranquillizers; local anesthetics e.g. benzocaine, procaine and tetracaine; antacids, such as calcium carbonate, aluminium hydroxide, basic aluminium carbonate and bismuth subcarbonate; and the vitamins e.g. ascorbic acid and the Vitamin B-complex.  The tablets can be laminated to form an inner-dosage and an outer-dosage component separated by an enteric layer thereby obtaining a delayed release.  Alternatively the two components system can be utilized for preparing tablets containing incompatible ingredients.