Patent GB-963428-A (GB)
IPC: C07J5/00
Filed: 1962-06-07
Abstract: The invention comprises steroids of the general formula: <FORM:0963428/C1/1> and the D 1-, D 6- and D 1,6-derivatives thereof wherein R1 represents hydrogen or a free or esterified hydroxyl group, R2 represents hydrogen or an acyl group derived from an aliphatic carboxylic acid containing up to 8 carbon atoms, R3 represents H, H or a -H, b -OH or =O, R4 represents hydrogen, chlorine or fluorine or a methyl group, X represents chlorine or fluorine, and Y represents hydrogen or fluorine, and the preparation thereof by reacting 16-halomethyl-steroids of the general formula: <FORM:0963428/C1/2> and the D 1-, D 6- and D 1,6-derivatives thereof, wherein R1, R3, R4, X and Y have the above significance, with hydrogen bromide in the presence of an inert solvent for example ether or dioxan, or a mixture thereof, benzene, toluene, tetrahydrofuran, acetone, chloroform, carbon tetrachloride or glacial acetic acid and, when required, acylating the 17x-hydroxy group in the product. The splitting of the 16a , 17a -oxido group with hydrogen bromide in an inert solvent may be carried out at any stage in a synthesis of steroids of the first general formula above. Thus the reaction with hydrogen bromide may be the final step or an intermediate step followed by one or more further reactions such as a microbiological 11-hydroxylation using fungi of the genus Curvularia, Stachylidium or Streptomyces to introduce an 11b -hydroxy group, or a fungi of the genus Absidia, Cunninghamella, Fusarium, Mucor, Penicillium or Rhizopus to introduce an 11a -hydroxy group; oxidation of an 11-hydroxy group to an 11-keto group; dehydrogenation at the 1,2-position either with chemical reducing agents such as 2,3-dichloro-5, 6-dicyano-benzoquinone or selenium dioxide or with microbiological reducing agents such as the microorganisms Bacillus sphaericus var. fusiformis, Corynebacterium simplex or Fusarium solani; dehydrogenation at the 6,7-position with chloranil; conversion of a 21-unsubstituted compound to a 21-acyloxy and a 21-hydroxy group by reaction with an alkaline solution of iodine, then an alkali metal acylate and, when required, saponification of the resulting 21-acylate; introduction of a 9a -fluorine atom by dehydration of an 11-hydroxy compound to form a D 9(11)-dehydro compound, conversion to 9b , 11b -oxido compound and reaction with hydrogen fluoride to form a 9a -fluoro-11b -hydroxy compound; and esterification of a 21- or 17a -hydroxy group.  Therapeutic compositions having antiphlogistic activity and which may be in the form of pills, tablets, dragees, suppositories, emulsions, suspensions or injectable solutions contain steroid compounds of the first general formula above.  16-Halomethyl-steroids of the second general formula above are prepared by reacting the corresponding 16-methylene-17a -hydroxy-steroids with N-chloro- or N-bromo-succinimide to form 16-chloro- or 16-bromo-methyl-16a -, 17a -oxido-steroids and, when required, treating the 16-bromo-methyl-16a -, 17a -oxido-steroids with silver or potassium fluoride to form 16-fluoro-methyl-16a -, 17a -oxido-steroids.  Specification 963,427 is referred to.