The nitration of canrenone with acetic anhydride/nitric acid

Article abstract of DOI:10.1016/S0039-128X(97)00073-1

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 H with most other reagents that were found to add at Δ⁶, 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 inhibitor), activity of II against Na⁺/K⁺-ATPase, the target enzyme of the cardioactive digitalis glycosides, which appears to indicate increased cardioactivity.