Reduction by a model of NAD(P)H. 25. A chiral model which induces high asymmetry

Abstract

Optically active '--methylbenzyl-l-propyl-2,4-dimethyl-1,4-dihydronicotinamide, a chiral model of NAD(P)H, has been synthesized and its absolute configuration has been determined. It has been found that the model compound exerts high enantiospecificity in the reduction of certain carbonyl compounds in the presence of magnesium perchlorate. The results seem to show that the enantiospecificity is controlled by both the electronic and steric effects of substituents in the carbonyl compounds. The polar substituent of the substrate undergoing reduction faces the carbamoyl group of the model compound in the transition state for the reaction.

Mechanistic Investigations on a Diynone Type Photoinitiator

“…The combined organic layers were washed with saturated NaHCO 3 (3 Â 20 mL), brine (20 mL), dried over Na 2 SO 4 , and the solvent was removed in vacuum. Distillation (65 8C per 25 mm Hg per liter, [31] bp: 59-60 8C per 18 mm Hg) gave 14.7 g (89%) of ester 2 as colorless liquid.…”

Thermodynamic characteristics of NADH/NAD+ analogues in acetonitrile: 2-methyl, 4-methyl and 2,4-dimethyl 1-benzyl-dihydronicotinamides and the corresponding pyridinium species

“…Efficient asymmetric reductions of prochiral ketones by NADH analogues, reacting in the absence of enzyme, have been reported using an approach that mimics the selective shielding of one of the diastereotopic C-4 hydrogens of NADH in the enzyme cavity by introducing a methyl substituent at C-4 of a 1,4-dihydronicotinamide (1)(2)(3)(4). However, in general, such a modification was accompanied by other changes in the structure.…”

“…However, in general, such a modification was accompanied by other changes in the structure. In most cases a second methyl substituent was present at the C-2 position of 1,4-dihydronicotinamide and one or both hydrogens of the amide were substituted by various alkyl groups in order to hinder its free rotation (1,2,4).…”

Enantioselective Radical Reactions

“…More than two decades ago, Ohno and co-workers synthesized optically active nicotinamide 55, which was considered a chiral model of NAD(P)H [43]. The model compound afforded high enantiospecificity in the reduction of certain carbonyl compounds and provided ∼ 70% ee.…”