GB996079A - 17ª‡,21-substituted methylenedioxy steroids and methods therefor - Google Patents

Abstract

The invention comprises steroids having at the 17, 20 and 21 positions the general formula <FORM:0996079/C2/1> wherein R1 represents an alkyl radical containing 1 to 3 carbon atoms and R represents an aliphatic hydrocarbon radical containing 1 to 9 carbon atoms, a cycloaliphatic hydrocarbon radical containing 4 to 6 carbon atoms, an arylaliphatic hydrocarbon radical containing 7 or 8 carbon atoms, a phenyl, a b -carboxyethyl, a b -carbomethoxyethyl or b -carbethoxyethyl radical, and the preparation thereof by reacting a 17a ,21-dihydroxy-20-keto-steroid having no free hydroxy group at the 16-position with an orthoester of the formula R-C(OR1)3 wherein R and R1 have the above significance in the presence of an acid catalyst and in solution in an organic solvent. The steroids of the above formula may contain at the 3-position a keto or hydroxy group, an alkoxy group of 1 to 3 carbon atoms, an alkoxyloxy group of 1 to 3 carbon atoms or a benzoyloxy group. Other substituents such as hydroxy, keto, halogen, ether and methyl groups, may be present, for example at positions 1,2,4,6,7,9,11 or 16. The steroid nucleus may be saturated or have one or more double bonds, for example in the 1 :2, 3 : 4, 4 : 5, 5 : 6 or 9 : 11 positions-particularly at positions 4 : 5, or 1 : 2 and 4 : 5 in which case the preferred steroids having a 3-keto group, an 11-keto or b -hydroxy group, and coupled with the 11b -hydroxy group an a -halogen atom-particularly fluorine, at the 9-position. Other substituents may occur at the 6- or 16-position, for example a 16a -acetoxy group. The particularly preferred steroids containing the structure detailed above have the general formula <FORM:0996079/C2/2> wherein R and R1 have the above significance, X represents a keto or b -hydroxy group, Y represents hydrogen or fluorine, W represents hydrogen or fluorine or the methyl group, and R2 represents hydrogen, an a or b -methyl group or an a -hydroxy group, and the corresponding 1 : 2-unsaturated derivatives thereof. If the product of the above process contains a 16b -bromine atom, this may be reacted with silver acetate to form a 16b -acetoxy substituent which may then be hydrolysed, for example with potassium carbonate, to form a 16a -hydroxy substituent. Specifications 963,829 and 996,080 are referred to.