GB915636A - Novel alkylated pregnadienes - Google Patents

Abstract

The invention comprises steroids of the general formula <FORM:0915636/IV (b)/1> wherein X represents hydrogen, fluorine, chlorine or bromine, Y represents =0 or H,b -OH, Z represents an alkyl radical having less than 6 carbon atoms, R represents hydrogen, an alkanoyl radical having not more than 8 carbon atoms, an aromatic or heterocyclic carboxylic acid acyl radical or a radical derived from a polybasic inorganic acid such as sulphuric and phosphoric acids, and A represents a bromine or chlorine atom, or a hydroxy radical, or the acyloxy radical of an aliphatic carboxylic acid p having less than 6 carbon atoms in the aliphatic radical or of an aliphatic or aromatic sulphonic acid, and the preparation of the 6-chloro and bromo steroids of the above general formula by reacting the corresponding 6-unsubstituted steroids with a chlorinating or brominating agent such as N-bromosuccinimide, N-bromoacetamide, N-chlorosuccinimide, bromine and chlorine, the preparation of the 6-hydroxy steroids of the general formula above by subjecting the corresponding 6-desoxy-steroids to the microbiological oxygenating activity of an organism of the genus Chaetomium, e.g. by an analogous procedure to that described in Specification 901,092, and the preparation of the 6-esters of the above general formula by esterifying the corresponding 6-hydroxy steroids. Prior to introducing a substituent at the 6-position, it is preferred to esterify any reactive hydroxyl groups which may be present e.g. at the 11- or 21-position. Thus, for example, in preparing 6-bromo-16a -methyl-prednisone, it is preferable to use a 21-ester of 16a -methylprednisone as the reactant. In those instances where there is an 11-hydroxy group such as when 16a -methylprednisolone is used as the reactant, the conditions necessary to esterify the 11-hydroxy group esterify both the 17a - and 21-hydroxy groups as well. Following the introduction of the 6-substituent, the ester groups may be hydrolysed chemically by means of dilute acid or microbiologically by means of Flavobacterium dehydrogenans, and in the case of 6-halo substituted compounds removal of the ester groups may also be carried out with a strong acid such as p-toluenesulphonic acid. Specification 796,769 is referred to.