Mechanisms of the Oxidations of NAD(P)H Model Hantzsch 1,4-Dihydropyridines by 2-Nitro-2-nitrosopropane

doi:10.3969/j.issn.0251-0790.2012.02.013

Abstract

Abstract: Hantzsch 1,4-dihydropyridine derivatives which contain 1,4-dihydropyridine structure of natural reduced nicotinamide adenine dinucleotide[NAD(P)H] coenzyme and possess a high biological activity as a class of useful drugs, can be chosen as models of NAD(P)H to react with NO or its donor to mimic the oxidation of NAD(P)H by NO in vivo. Herein, 4-substituted derivatives of Hantzsch 1,4-dihydropyridine were treated by 2-nitro-2-nitrosopropane to give the corresponding pyridine derivatives. Replacement of HEH by N-d-HEH and 4,4'-2d-HEH to react with 2-nitro-2-nitrosopropane gave the observed kinetic isotope effects of 1.03 and 1.78. The study of the redox potentials(cyclic voltametry) of the two reactants indicated that the oxidation of HEH by 2-nitro-2-nitrosopropane initiated by one-electron transfer was extremely unfavorable in thermodynamics. In addition, the ineffectiveness of p-dinitrobenzene on the reaction can also support it. These results indicate that the oxidation of HEH by 2-nitro-2-nitrosopropane is initiated by nitrosation to give the corresponding N-nitroso compound, which is subsequently subjected to two steps of homolytic cleavage to afford the aromatized Hantzsch pyridine. We believe that the present work will stimulate the investigations of the chemical features of C-nitroso compounds and its role in biological and medicinal chemistry.

Key words: Nitric oxide donor, Hantzsch 1,4-dihydropyridine, Oxidative reaction, Electrochemistry, Isotope effect

CLC Number:

O621.1

TrendMD:

LI Xin, DONG Nan, CHENG Jin-Pei. Mechanisms of the Oxidations of NAD(P)H Model Hantzsch 1,4-Dihydropyridines by 2-Nitro-2-nitrosopropane[J]. Chem. J. Chinese Universities, 2012, 33(02): 288.

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