Oxidation of Hantzsch 1,4-dihydropyridines of pharmacological significance by electrogenerated superoxide.
OBJECTIVE
To study the reaction of a series of Hantzsch dihydropyridines with pharmacological significance such as, nifedipine, nitrendipine, nisoldipine, nimodipine, isradipine and felodipine, with electrogenerated superoxide in order to identify products and postulate a mechanism.


METHODS
The final pyridine derivatives were separated and identified by gas chromatography/mass spectrometry (GC-MS). The intermediates, anion dihydropyridine and the HO2*/HO2- species, were observed from voltammetric studies and controlled potential electrolysis was used to electrogenerate O2*-.


RESULTS
The current work reveals that electrogenerated superoxide can quantitatively oxidize Hantzsch dihydropyridines to produce the corresponding aromatized pyridine derivatives.


CONCLUSIONS
Our results indicate that the aromatization of Hantzsch dihydropyridines by superoxide is initiated by proton transfer from the N1-position on the 1,4-dihydropyridine ring to give the corresponding anion dihydropyridine, which readily undergoes further homogeneous oxidations to provide the final aromatized products. The oxidation of the anionic species of the dihydropyridine is more easily oxidized than the parent compound.
Ortiz
M E
ME
Bioelectrochemistry Laboratory, Chemical and Pharmaceutical Sciences Faculty, University of Chile, P.O. Box 233, Santiago 1, Chile.
Núñez-Vergara
L J
LJ
Camargo
C
C
Squella
J A
JA
D002121:Calcium Channel Blockers / Q000737:chemistry; D015736:Felodipine; D009543:Nifedipine / Q000737:chemistry; D009553:Nimodipine / Q000737:chemistry; D009568:Nitrendipine / Q000737:chemistry; D013481:Superoxides
D002121:Calcium Channel Blockers; D013481:Superoxides; D009553:Nimodipine; D009568:Nitrendipine; D009543:Nifedipine; D015736:Felodipine