GB839698A - Steroids and the synthesis thereof - Google Patents

Abstract

The invention comprises steroid compounds of the general formula <FORM:0839698/IV (b)/1> and <FORM:0839698/IV (b)/2> wherein the 1,2-position is saturated or double bonded, X represents a halogen, and R represents hydrogen and R1 represents a b -hydroxy group or R and R1 together represent a keto group, and the preparation of the 9,11-epoxy compounds by reacting the corresponding 21-chloro, bromo or alkane sulphonyloxy compound with potassium fluoride in an organic solvent of high dielectric constant such as dimethyl formamide or dimethylsulphoxide, and the preparation of the 9a -halogeno compound by treating the corresponding 9b ,11b -epoxy compound with a hydrogen halide. The invention also comprises a process for the preparation of the 9a -fluoro compounds of the above general formula by treating the corresponding 9a - fluoro - 21 - chloro, bromo or alkanesulphonyloxy compounds with potassium fluoride in an organic solvent of high dielectric constant. In all the processes referred to above, products of the first general formula above containing an 11b -hydroxy group may be oxidized to the corresponding 11-keto compound or by treatment with a hexavalent chromium compound e.g. chromic acid, in an acid medium e.g. glacial acetic acid. The compounds of the second general formula may also be prepared from the corresponding 21-g -11b -hydroxy compounds, g is Cl, Br or alkanesulphonyloxy, by reacting these compounds with potassium fluoride in an organic solvent of high dielectric constant to yield the corresponding 21-fluoro-11b -hydroxy compounds, treating these compounds with an alkane sulphonyl chloride to form the corresponding 21-fluoro- D 9(11)-derivatives, reacting these derivatives with a bromoamide or -imide, e.g. N-bromo-acetamide, to form the corresponding 9a -bromo-21-fluoro-11b -hydroxy-derivatives, and treating these derivatives with a salt of a strong base and a weak acid, e.g. potassium acetate. The 21-fluoro- D 9(11)-derivatives may also be formed from the corresponding 11b ,21-dihydroxy di(alkanesulphonic acid ester) derivatives by treatment with potassium fluoride in an organic solvent of high dielectric constant. In the examples the following compounds are prepared: 9a ,21 - difluoro - D 4 - pregnene - 11b , 17a - diol - 3,20 - dione, 9a ,21 - difluoro - D 4-pregnene - 17a - ol - 3,11,20 - trione and 21-fluoro - 9b ,11b - epoxy - D 4 - pregnene - 17a -ol - 3,20 - dione, and the corresponding D 1,4-pregnadienes, 9a - chloro (bromo and iodo)-21 - fluoro - D 4 - pregnene - 11b ,17a - diol - 3,20-dione, 9a - chloro (bromo and iodo) - 21-fluoro - D 4 - pregnene - 17a - ol - 3,11,20-trione, 9a - chloro - 21 - fluoro - D 1,4 - pregnadiene - 11b ,17a - diol - 3,20 - dione, and 9a -chloro - 21 - fluoro - D 1,4 - pregnadiene - 3,11, 20-trione.