The nitration of canrenone with acetic anhydride/nitric acid

Abstract 3-Oxo-17α-pregna-4,6-diene-21,17-carbolactone (canrenone, II) is produced from the potassium salt of 17-hydroxy-3-oxo-17α-pregna-4,6-diene-21-carboxylic acid (I) by acid catalyzed lactonization. II reacts with acetic anhydride/nitric acid to give one main product (III) and some minor products. The structure of III was determined by chemical and spectral analysis to be the 4-nitro derivative of canrenone. This result is in contrast to the known reactions of II with most other reagents that were found to add at Δ 6 , and also in contrast to the reactions of acetic anhydride/nitric acid with alkenes. Electrophilic substitution at the ambident C4 is discussed as the reaction path. The 4-nitro group enhances the inhibitory activity of II against Na + K + - ATPase , the target enzyme of the cardioactive digitalis glycosides, which appears to indicate increased cardioactivity.