GB969300A - New steroids of the androstane series and process for their production - Google Patents

Abstract

The invention comprises compounds of the formula: <FORM:0969300/C1/1> (wherein R1 is methyl, ethyl, n-propyl or isopropyl; R2 is methyl or ethyl; and R3 is hydrogen or an alkanoyl radical of at most 6 carbon atoms) and their 1-dehydro derivatives; and their preparation by (1) oxidizing a corresponding D 5 -3- hydroxy steroid or a 3-acylate thereof, optionally after saponification, with a mild chemical oxidizing agent or with a suitable micro-organism; or (2) dehydrohalogenating a corresponding ring A saturated 4- or 5-haloandrostane; or (3) isomerizing a corresponding D 5 -3- keto-androstene or a 3-keto derivative thereof e.g. a ketal; or (4) dehydrogenating a 1, 2-saturated compound of the above formula or dehydrohalogenating a ring A saturated 2,4-dihalo-androstane to form the corresponding D 1, 4-androstadiene; or (5) esterifying a free 17a -hydroxy-androstene of the above formula or saponifying a 17-ester. Process (1) may be effected with an Oppenauer oxidant or with a micro-organism such as Flavobacterium dehydrogenans, or with a 1,2-dehydrogenating micro-organism such as Bacillus sphacriens var. fusiformis, Corynebacterium simplex or Fusarium solani although these last-named are generally only used if a 1,2-double bond is to be introduced at the same time. For the isomerization process an acid or alkaline agent or iodine may be used, and if an acid agent is used the keto group may be functionally modified. 1,2-Dehydrogenation may be effected chemically, for example with a quinone or selenium dioxide, or micro biologically as indicated above. Examples are given. Starting materials of the general formulae: <FORM:0969300/C1/2> <FORM:0969300/C1/3> <FORM:0969300/C1/4> <FORM:0969300/C1/5> are prepared from dehydro, epi-androsterone 3-acylates. Bromination gives the corresponding 7-bromo compounds, these are converted into the 7-hydroxy compounds, these on etherification and reaction with alkyl magnesium halides give compounds of the Formula II, addition of hydrogen halide to the 3-hydroxy -5- dehydro compounds and subsequent oxidation of the 3-hydroxy group gives compounds of the Formula III, oxidation of compounds II under non-isomerizing conditions gives compounds of the Formula IV, and compounds of the Formula V are prepared by catalytic hydrogenation of the compounds II, oxidation of the products to 3-ketones and subsequent halogenation. The 7-alkoxy-androstene derivatives of the invention, which are anabolic agents, may be made up into pharmaceutical compositions with suitable carriers. These may take the form of solutions, suspensions, emulsions, implants, tablets, dragees, ointments or creams, and may contain preservatives, stabilizers, wetting agents, salts for varying the osmotic pressure or buffers.