Patent GB-826629-A (GB)
Title: Improvements in or relating to steroids and the manufacture thereof
IPC: C07J5/00
Filed: 1957-03-11
Abstract: The invention comprises a compound of the formula <FORM:0826629/IV (b)/1> wherein R1 is an 11b -hydroxy or an 11-keto group, R11 is hydrogen or the acyl radical of a hydrocarbon carboxylic acid containing 1-12 carbon atoms inclusive, and R111 is a phenyl radical or a lower alkyl radical containing one to six carbon atoms inclusive and the preparation thereof by dehydrating a compound of the formula <FORM:0826629/IV (b)/2> with an alkali metal base and then if desired esterifying the resulting 11-oxygenated-6-phenyl or 6 - alkyl - 17a , 21 - dihydroxy - 4 - pregnene3,20-dione with an anhydride or acid halide of an organic carboxylic acid containing 1-12 carbon atoms inclusive to obtain the corresponding 21-acylate.  Sodium hydroxide, potassium hydroxide, barium hydroxide, calcium hydroxide are operative in methanol, ethanol or dioxane.  Excess amount of base results in the 6a -epimer.  Alternatively dehydration may be effected with an acid or thionyl chloride.  In yet another method the complex obtained by reacting 11-oxygenated-5a ,6a -oxido-17a ,21-dihydroxy - allopregnane - 3,20 - dione 3,20 - bis (alkylene ketal) with a Grignard reagent, is decomposed, hydrolysed and dehydrated in one step by the addition of acid, e.g. dilute aqueous sulphuric acid. 21-Acylates are obtained by conventional procedures.  Examples describe the preparation of 6(a  and b )-methylhydrocortisone, 6a  - ethylhydrocortisone, 6a  - methyl11a ,17a ,21 - trihydroxy - 4 - pregnene - 3,20dione, 6a -methyl and 6a -phenylcortisone, 6a methylhydrocortisone from 6b -methylhydrocortisone, 21-acetates, benzoates, trimethylacetates, propionates, butyrate, hexanoates, heptanoates, octanoates, phenylacetates, b cyclopentylpropionates, 2-furoates, nicotinates, toluenesulphonates, p - chlorobenzene - sulphonates, cinnamates, triethylacetates, dineopentylacetates of cortisone and hydrocortisone bearing a 6-methyl, ethyl, propyl, isopropyl, butyl, pentyl, hexyl or phenyl substituent, 6a methylhydrocortisone 21 - hemisuccinate, 6a methylhydrocortisone 21-(b ,b -dimethyl glutarate) the corresponding 6a -methyl cortisone compounds and their sodium salts.  Specification 826,630 is referred to.ALSO:6 - Alkylhydrocortisones, 6 - phenylhydrocortisone and the 21-esters thereof are employed in capsules, tablets, liquid suspensions or solutions, ointments, bougies, lotions, jellies and drops.  Tablets are exemplified incorporating 6-methylhydrocortisone and also antibiotics, e.g. tetracycline, chlortetracycline, oxytetracycline, chloramphenicol, penicillin and novobiocin.  Sulpha drugs, aspirin and vitamins may also be present.  An ointment is exemplified incorporating neomycin sulphate and 6a -methylhydrocortisone.  The neomycin sulphate may be replaced by polymyxin B sulphate, bacitracin, gramicidin and tyrothricin. Instead of 6-methylhydrocortisone, 21-esters thereof, e.g. the 21-acetate, propionate, butyrate, benzoate, phenylacetate, phenyl propionate, dineopentylacetate, t-butylacetate and trimethylacetate may be employed.  For parenteral use the water-soluble esters of polybasic acids and their salts are employed.  Specification 826,630 is referred to.