Patent GB-953711-A (GB)
Title: Improvements in or relating to steroids
IPC: C07C51/567
Filed: 1960-12-08
Abstract: The invention comprises 6a -fluoromethyl compounds of the formula: <FORM:0953711/C2/1> and the corresponding D 1,4 D 4,6 and D 1,4,6 compounds wherein W is the carbonyl radical or the b -hydroxymethylene radical; X1 is hydroxy or O-Acyl, the term Acyl representing the acyl radical of a hydrocarbon carboxylic acid containing from 1-12 carbon atoms, inclusive; Y is hydrogen or a -methyl; Y11 ishydrogen, a -methyl, b -methyl or a -hydroxy and Z111 is hydrogen or halogen, compounds of the formula: <FORM:0953711/C2/2> wherein Y, Y11 and W are as defined above, Z11 is hydrogen, fluorine or chlorine and R is a hydrocarbon radical containing 1-10 carbon atoms and the corresponding D 1,4, D 4,6 and D 1,4,6 compounds, compounds having the formulae: <FORM:0953711/C2/3> <FORM:0953711/C2/4> wherein Y, Y11 and Ac are as defined above and processes for the preparation thereof which comprise (1) reacting a starting compound of the formula: <FORM:0953711/C2/5> wherein Y and Y1 are as above defined with formaldehyde in the presence of a strong acid to produce the corresponding 17 :  20, 20 : 21-bismethylenedioxy-4-pregnene-3, 11-dione; (2) treating the thus produced compound with an alkenyl acylate in the presence of an acid catalyst to give a 17, 20: 20, 21-bismethylenedioxy-3, 5-pregnadiene-11-one 3-acylate; (3) reducing the thus-produced compound to give a 17, 20: 20,21-bismethylenedioxy-5-pregnene-3b , 11b -dihydroxy-3-acylate; (4) hydroxymethylating the thus obtained compound at the 6-position by reacting said compound with carbon monoxide and hydrogen in the presence of an 'oxo' catalyst under superatmospheric pressure to produce 17, 20: 20, 21-bismethylenedioxy-6a -hydroxymethyl-5a -pregnane 3-acylate; (5) reacting the thus-produced compound with an organic sulphonyl halide to form the corresponding organic sulphonate ester which is reacted with an alkali metal fluoride to yield 17, 20: 20, 21-bismethylenedioxy-6a -fluoromethyl-3b , 11b -dihydroxy-5a -pregnane, (6) oxidising the thus produced compound with aluminium alkoxide to give the corresponding 17, 20: 20, 21-bismethylenedioxy-6a -fluoromethyl -11b -hydroxy-5a -pregnane-3-one, (7) dehydrogenating the thus obtained compound in the 1,2 and 4, 5 positions to obtain the corresponding 17, 20: 20: 21-bismethylenedioxy-6a -fluoromethyl-11b -hydroxy-1, 4-pregnadiene-3-one, (8) hydrolysing the thus obtained compound to obtain the corresponding 6a -fluoromethyl-11b , 17a , 21-trihydroxy-1, 4 pregnadiene-3, 20-dione and then if desired acylating to produce the corresponding 21-ester or if desired acylating to produce the corresponding 21-ester or (9) selectively hydrogenating at the 1, 2 position the thus-produced compound to produce the corresponding 6a -fluoromethyl-11b , 17a , 21-trihydroxy-4-pregnene-3, 20-dione and if desired acylating to produce the 21-ester. Alternatively the 17, 20: 20, 21-bismethylenedioxy-6a -fluoromethyl-11b -hydroxy -5a -pregnan-3-one obtained above may be halogenated in acid medium with chlorine or bromine, and dehydrohalogenated with sodium iodide to obtain 17, 20: 20, 21 -bismethylenedioxy-6a -fluoromethyl-11b -hydroxy-4-pregnen-3 -one which may be hydrolysed to obtain 6a -fluoromethyl-11b , 17a -21-trihydroxy-4-pregnen-3, 20-dione and if desired acylated to produce the corresponding 21-ester. A double bond may be introduced in the 1, 2-position by means of selenium dioxide or a suitable fungus e.g. of the genus Septomyxa and in the 6, 7-position by means of chloranil. In addition the D 1, 4 compounds may be converted into D 4 compounds by fermentative hydrogenation. A hydroxyl group may be introduced into compounds in which Y1 represents H by means of Streptomyces roseochromogenus. The 9, 11-unsaturated compounds are obtained from the corresponding 11b -hydroxy compounds by dehydration. A 9-halogen substituent may be introduced into the products by conventional procedures. The 21-sulphonates are obtained from the corresponding 21-hydroxyl compounds by treatment with an organic sulphonyl halide. Subsequent treatment of the 21-sulphonate with potassium fluoride gives a 21-fluoro derivative, and with sodium iodide a 21-iodo derivative is obtained. The 21-iodo compound may be reduced to obtain a 21-unsubstituted compound. Specification 874,213 is referred to.ALSO:Pharmaceutical compositions having antiinflammatory, salt and water regulating, pituitary-inhibiting, progestational and anti-anabolic activities and containing 6a -fluoromethyl compounds of the formula <FORM:0953711/A5-A6/1> or the corresponding D 1,4- D 4,6 or D 1,4,6 compounds wherein W is the carbonyl radical or the b -hydroxymethylene radical; X1 is hydroxy or O Acyl, the term Acyl representing the acyl radical of a hydrocarbon carboxylic acid containing 1-12 carbon atoms, Y is hydrogen or a -methyl, Y11 is hydrogen, a -methyl, b -methyl or a -hydroxy and Z111 is hydrogen or halogen, with or without the known antibiotics such as the penicillins, neomycin, tetracyclin, chloramphenicol, and novobiocin and/or antifungal agents such as grieseofulvin, are administered systemically and/or topically in ointments, creams, lotions, sprays, tablets, suspensiona and solutions.  Specification 874,213 is referred to.