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 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 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.
Megges
R
R
Max-Delbrück-Center for Molecular Medicine, Berlin-Buch, Germany.
Weiland
J
J
Undeutsch
B
B
Büchting
H
H
Schön
R
R
D019342:Acetic Acid / Q000737:chemistry*; D002192:Canrenone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D009566:Nitrates / Q000737:chemistry*; D017942:Nitric Acid / Q000737:chemistry*; D013055:Spectrophotometry, Infrared; D013056:Spectrophotometry, Ultraviolet; D014466:Ultraviolet Rays
C110501:4-nitrocanrenone; D009566:Nitrates; D017942:Nitric Acid; D002192:Canrenone; D019342:Acetic Acid