GB887815A - Steroids - Google Patents

Abstract

The invention comprises 11a - and 11b -acylamino - D 4 - pregnene - 17a , 21 - diol - 3, 20 - diones and the corresponding D 1,4-pregnadienes and 11a -amino-steroids of the pregnane and allopregnane series of the general formula <FORM:0887815/IV (b)/1> wherein X represents hydrogen or an a -hydroxy group, Y represents hydrogen or a hydroxyl or alkanoyloxy group, Z represents a hydroxy, keto or ketal group and R represents hydrogen or an alkanoyl group (the alkanoyloxy and alkanoyl groups are saturated aliphatic groups having not more than 4 carbon atoms) and the corresponding N-acylated compounds, and a process for the preparation of 11a and 11b -amino-steroids of the pregnane and allopregnane series of the above general formula wherein X, Y, Z and R have the above significance, by reducing the corresponding 11-oximino compounds by any method known for the direct reduction of an oxime to the corresponding amine, and, if necessary, removing the 20-ketal group to form a 20-keto group. The above process may be extended in that the 11-amino group may be acylated to form the corresponding 11-acylamino compounds. When the above reduction process is carried out with sodium in alcohol or sodium amalgam in an aqueous medium on 11a -amino-steroids is formed and when the reduction is carried out with lithium aluminium hydride or by catalytic hydrogenation in an acid medium an 11b -amino-steroid is formed. The 11a -amino-pregnane-3a ,17a ,20b -triol may be acylated to form an N-aryl-3,20-diacyloxy compound the ester groups of which may be hydrolysed by treatment with refluxing aqueous methanolic sodium hydroxide for a short period to form an 11a -acylaminopregnane-3a ,17a ,20b -triol. The latter compound or the corresponding 11b -acylamino compound may be converted to 11a -acylaminopregnane-17a -ol-3,20-dione or the corresponding 11b -acylamino-compound by oxidising with chromium trioxide in pyridine with N-bromo-acetamide or with N-bromo-succinimide. Further treatment by selectively reducing the 3-keto group to form an 11a (or b )-acylamino-pregnane-3a ,17a -diol-20-one, e.g. with sodium borohydride or hydrogen in the presence of Raney nickel, brominating to form the corresponding 21-bromo compound, reacting with potassium acetate to form 11a (or b )-acylamino - 21 - acetoxy - pregnane - 3a , 17a - 3,20-dione, brominating at C4 to form the corresponding 4-bromo-compound, dehydrobrominating to form 11a (or b )-acylamino-21-acetoxy-D 4-pregnene-17a -ol-3,20-dione, and hydrolysing with acid or alkali forms 11a -acylamino-D 4-pregnene-17a ,21-diol-3,20-dione, and optionally dehydrogenating with selenium dioxide or dehydrogenating by means of a biochemical method forms 11a (or b )-acylamino-D 1,4-pregnadiene-17a ,21-diol-3,20-dione. Detailed examples are given.