Synthesis of proteogenic amino acid-based NAD analogs

Abstract

Nicotinamide adenine dinucleotide (NAD) analogs have been prepared for diverse applications especially as alternative redox cofactors for NAD-dependent enzymes. Herein, 14 NAD analogs based on proteogenic amino acids were synthesized in 20–98% isolated yields through the Zincke reaction in the presence of triethylamine. Their physicochemical properties including spectroscopy and redox potential were characterized. Preliminary activity screening results showed that a few reduced analogs were effective as cofactors for a mutant cytochrome P450 enzyme to facilitate fatty acid hydroxylation.