1.Stereoselective synthesis of nicotinamide β-riboside and nucleoside analogs
Palmarisa Franchetti*, Michela Pasqualini, Riccardo Petrelli. Bioorganic & Medicinal Chemistry Letters 14 (2004) 4655-4658
Nicotinamide riboside (β-NAR) is an intermediate in one biosynthetic pathway by which nicotinamide is converted into NAD. In fact, nicotinamide or nicotinamide riboside derived from degradation of NAD can be reused by nicotinamide phosphoribosyl transferase or ribosylnicotinamide kinase, respectively, to form the ribotide NMN that is adenylated to NAD by nicotinamide mononucleotide adenylyltransferase (NMNAT). Human NMNAT is an indispensable enzyme in both denovo and salvage/recycling pathways for NAD biosynthesis, catalyzing the conversion of NMN or its deamidated form NaMN into NAD or NaAD, respectively. On the other hand, it is known that many bacterial NMNATs strongly prefer the deamidated NaMN as a substrate. NAD is a co-factor in numerous enzyme-catalyzed redox reactions in all living organisms and plays a fundamental role in cellular metabolic processes. It is crucial thus that proper level of NAD are regulated and maintained for cellular survival. There is evidence that hNMNAT is weakly expressed in tumor cells, determining thus interest in the enzyme as a target for anticancer drugs. In this respect, some nicotinamide riboside analogs have been described as antitumor agents involving their metabolic conversion to NAD analogs by NMNAT activity.