Patent GB-912015-A (GB)
Title: Steroid compounds
IPC: C07J5/00
Filed: 1959-07-01
Abstract: The invention comprises steroids of the general formulae <FORM:0912015/IV (b)/1> <FORM:0912015/IV (b)/2> wherein X represents hydrogen or fluorine, R represents a keto or p  hydroxy group, R1 represents hydrogen or an alkanoyl group containing 1 to 6 carbon atoms and the 16-methyl group may be in the a - or b -position; the preparation of the compounds of the first general formula wherein X represents hydrogen by treating the required D 5-11-oxygenated-17 - 20,20 - 21 bismethylenedioxy-16-methyl-3-ethylenedioxy-pregnene with a peracid to produce the corresponding 11-oxygenated-17-20, 20 - 21 - bismethylenedioxy - 5a ,6a  - epoxy-16-methyl-3-ethylenedioxy-pregnane, reacting this compound with hydrofluoric acid to form the corresponding 11-oxygenated-17,20,20,21-bis-methylenedioxy - 5a  - hydroxy - 6b  - fluoro-16-methyl-3-ethylenedioxy-pregnane, treating this compound with acid to form the corresponding D 4-11-oxygenated-17,20,20-21-bismethylenedioxy - 6b  - fluoro - 16 - methyl-pregnen-3-one, serially contacting said latter steroid with aqueous acetic or formic acid and a mineral acid under anhydrous conditions which removes the bismethylenedioxy group and inverts the 6b -fluoro substituent to form the desired 21-free hydroxy compound (this step may be carried out in two stages, i.e. inversion of the 6b -fluoro substituent with mineral acid and then removal of the bismethylenedioxy group with acetic or formic acid) and, when required, acylating this compound to form the corresponding 21-acylate; the preparation of the compounds of the second general formula wherein X represents fluorine by treating a C21 C1-6 alkanoyl ester of D 4,9(11)-6a -fluoro-16-methyl - pregnadiene - 17a ,21 - diol-3,20-dione (which may be optionally prepared by treating the corresponding D 4-6a -fluoro-16-methyl-11b , 17a  - dihydroxy - 3,20 - diketo-21-alkanoyloxypregnene with methane sulphonyl chloride in the presence of a base) with N-bromosuccinimide to produce the corresponding ester of D 4 - 6a  - fluoro-9a -bromo-16-methyl-pregnene-11b ,17a ,21-triol-3, 20-dione, successively treating the latter compound with sodium acetate (to form a 9b ,11b -oxido compound) and then hydrogen fluoride to form a C21 C1-6 alkanoyl ester of D 4-6a ,9a -difluoro-16-methyl-pregnene-11b ,17a ,21-triol-3, 20-dione, when required, oxidising this 11b -hydroxy compound to form the corresponding 11-keto compound and, when required, saponifying the 11b -hydroxy or 11-keto C21 C1-6 alkanoyl ester to form the corresponding free 21-hydroxy compound; a process for the preparation of compounds of the second general formula by dehydrogenating compounds of the first general formula with selenium dioxide; and a process for the compounds of the second general formula wherein X represents fluorine and R1 represents the alkanoyl group by treating D 1,4-11b ,17a -dihydroxy - 21 - acyloxy-6a -fluoro-16-methyl-3,20-diketo-pregnadiene (which may be prepared by the dehydrogenation process previously referred to) with methane sulphonyl chloride in the presence of a base to form D 1,4,9(11) - 17a  - hydroxy - 21-acyloxy-6a -fluoro-16-methyl - 3,20 - diketo-pregnatriene, reacting this compound with N-bromosuccinimide to form D 1,4 - 6a  - fluoro - 9a  - bromo - 11b ,17a  - dihydroxy - 21 - acyloxy-3,20-diketo-16-methylpregnadiene and reacting this compound with sodium acetate and hydrogen fluoride.  D 5-17-20,20-21-bismethylenedioxy-11-keto (or hydroxy) - 16(a  or b ) - methyl-3-ethylenedioxypregnenes are prepared by treating the required 11,16 - disubstituted-17a ,21-dihydroxy-3,20-diketo-4-pregnene with formaldehyde to form the corresponding 11,16-disubstituted-17a  - 20, 20 - 21 - bismethylenedioxy-3-keto-4-pregnene, and treating this compound with ethylene glycol in the presence of p-toluenesulphonic acid.  Specifications 877,085 and 906,443 are referred to.