GB898295A - Improvements in or relating to steroids and the manufacture thereof - Google Patents

Abstract

The invention comprises compounds represented by the formulae <FORM:0898295/IV (b)/1> wherein X is hydrogen, fluorine or chlorine and Y is b -hydroxymethylene or carbonyl, process for the preparation of 6a , 16b -dimethyl-11-ketoprogesterone by (1) diketalising 11a -hydroxy-16b -methylprogesterone with a lower alkylene glycol; (2) epoxidising the 5(6)-double bond of the thus produced diketal with a peracid to produce a 5a , 6a -epoxide; (3) reacting the thus produced compound with a methyl Grignard reagent to produce a 5a -hydroxy-6b -methyl compound; (4) hydrolysing the ketal groups with acid to give 5a , 11a - dihydroxy - 6b , 16b - dimethylallo - pregnane-3,20-dione; (5) oxidising the 11-hydroxy group to an 11-keto group with an oxidising agent; and (6) dehydrating the 5a -hydroxy group, to produce 6a , 16b -dimethyl-11-ketoprogesterone; and a process for the preparation of a compound having the formula <FORM:0898295/IV (b)/2> wherein the dotted line in the 1,2-position represents an optional single bond, X is hydrogen, chlorine or fluorine and Y is carbonyl or b -hydroxymethylene by subjecting a compound having the formula <FORM:0898295/IV (b)/3> wherein the dotted line, X and Y are as defined above to reduction by known methods for the removal of iodine, e.g. with sodium thiosulphate. 3, 11 - Diketo - 6a , 16b - dimethyl - 4, 17 (20) - pregnadien-21-oic acid alkyl ester is obtained by diglyoxalating, trihalogenating, rearranging and dehydrating either 6a , 16b - dimethyl - 11 - ketoprogesterone or 5a -hydroxy-6b ,16b -dimethylallopregnane-3,11,20-trione. By protecting the 3-keto group, e.g. by forming a 3-enamine, the 21-carboxylic acid ester group may be reduced with lithium aluminium hydride to obtain 6a ,16b -dimethyl - 11b , 21 - dihydroxy - 4, 17 (20) - pregnadien-3-one into which a D 1-double bond may be introduced either microbiologically or with selenium dioxide. Specifications 749,195, 761,490, 761,527, 761,528, 779,001 and 779,002 also are referred to.ALSO:Pharmaceutical compositions having anti-inflammatory and progestational activity comprise compounds having the formulae <FORM:0898295/VI/1> wherein X is hydrogen, fluorine or chlorine, and Y is b -hydroxymethylene or carbonyl, antibiotics e.g. penicillin, neomycin, chloramphenicol and novobiocin, and a pharmaceutical carrier. They are administered orally, intramuscularly or topically in tablets, sterile suspensions and ointments. Specifications 749,195, 761,490, 761,527, 761,528, 779,001 and 779,002 also are referred to.