Development of Water‐Soluble Nicotinamide Coenzyme Biomimetics for Improved Catalytic Efficiency

Abstract Two series of novel nicotinamide coenzyme biomimetics were synthesized as potential replacements for the natural cofactor nicotinamide adenine dinucleotide (phosphate) in its reduced form [NAD(P)H] and the widely used 1‐benzyl‐1,4‐dihydronicotinamide (BNAH). Their potentials and water solubility were assessed and applied to catalyze the reduction of α,β ‐epoxyketones, with some showing enhanced water solubility and hydride transfer capabilities compared to NAD(P) and BNAH. Furthermore, these coenzymes were utilized in the biocatalytic reduction of a fluorescent probe, and the resulting increase in fluorescence intensity indicated superior reducing activity compared to that of natural cofactors.