The nitration of canrenone with acetic anhydride nitric acid

3-Oxo-17 alpha-pregna-4,6-diene-21,17-carbolactone (canrenone, II) is produced from the potassium salt of 17-hydroxy-3-oxo-17 alpha-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 Delta(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 pain. 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. (C) 1997 by Elsevier Science Inc.