REDUCED NICOTINAMIDE ADENINE-DINUCLEOTIDE (NADH) MODELS .14. METAL-ION CATALYSIS OF THE REDUCTION OF ALPHA,BETA-UNSATURATED KETONES BY 1,4-DIHYDROPYRIDINES - MODEL OF DELTA-4-3-KETOSTEROID REDUCTASES

The reduction of (E)-2-, (E)-3-and (E)-4-cinnamoylpyridines by 1,4-dihydropyridine derivatives, to the corresponding dihydro ketones, is catalyzed by Zn2+ and Mg2+ ions. Kinetic measurements show that the rate of reduction is fastest in the case of the 2 isomer, in which the metal ion is simultaneously complexed with the nitrogen and the oxygen sites. The latter example is regarded as a model of electrophilic catalysis of the NADH-dependent enzymatic reduction of Δ4-3-keto-steroids. Reduction of the above-mentioned substrates, as well as that of the (corresponding) isomeric β-benzoylvinylpyridines, with 1,4-dihydropyridine-4,4-d2 reveals that in all reduction products the deuterium atom is located at the β position with respect to the carbonyl group. Furthermore, in the reaction of (E)-2-cinnamoylpyridine with N-benzyl-l,4-dihydronicotinam-ide-4,4-d2 the primary kinetic isotope effect shows that C(4)-H bond cleavage is involved in the rate-determining step. These results are interpreted in terms of a mechanism involving either a hydride transfer or a sequential transfer of an electron (e) and a hydrogen atom (H•). © 1979, American Chemical Society. All rights reserved.