Syntheses and chemical properties of β-nicotinamide riboside and its analogues and derivatives

Abstract

The β-anomeric form of nicotinamide riboside (NR+) is a precursor for nicotinamide adenine dinucleotide (NAD+), a redox cofactor playing a critical role in cell metabolism. Recently, it has been demonstrated that its chloride salt (NR+Cl−) has beneficial effects, and now NR+Cl− is available as a dietary supplement. Syntheses and studies of analogues and derivatives of NR+ are of high importance to unravel the role of NR+ in biochemical processes in living cells and to elaborate the next generation of NR+ derivatives and conjugates with the view of developing novel drug and food supplement candidates. This review provides an overview of the synthetic approaches, the chemical properties, and the structural and functional modifications which have been undertaken on the nicotinoyl riboside scaffold.

Electrochemical Characterization of Nicotinamide Riboside

“…[2,3] In particular, NAD + determines the activity of enzymes, such as sirtuin enzymes, which are crucial to cellular metabolism, cell survival, and DNA repair. [2,3,6] This has become apparent as the decline of the cofactor has been attributed to various disease states, such as cardiovascular disease, diabetes, and kidney failure. [2,3,6] This has become apparent as the decline of the cofactor has been attributed to various disease states, such as cardiovascular disease, diabetes, and kidney failure.…”

“…The general consensus has been that vitamin B 3 supplementation improves one's healthspan, rather than one's lifespan. [2,6,8] As companies battle over rights to sell NR exclusively, scientists are exploring the inherent value of the supplement over the analogs previously listed. [15] The inevitable decline of NAD + is being combated through the use of oral supplements of the vitamin B 3 complex such as nicotinamide, nicotinic acid (niacin), nicotinamide mononucleo-tide (NMN), and NR, Figure 1, as well as sirtuin activating compounds like resveratrol.…”

“…[1] NAD + /NADH cofactor is critical for the success of the catalytic behavior of dehydrogenase enzymes, while also functioning as a biomarker within various systems and a regulatory agent for post-translational protein modifications. [2,3] In particular, NAD + determines the activity of enzymes, such as sirtuin enzymes, which are crucial to cellular metabolism, cell survival, and DNA repair. [4,5] The pyridine nucleotide is essential for the production and consumption of energy, and decreases in abundance as we age.…”

“…[4,5] The pyridine nucleotide is essential for the production and consumption of energy, and decreases in abundance as we age. [2,3,6] This has become apparent as the decline of the cofactor has been attributed to various disease states, such as cardiovascular disease, diabetes, and kidney failure. [7] To highlight physiological relevance further, sirtuin enzymes use the cofactor to deacetylate the lysine groups of histones and proteins of various subcellular components.…”

“…[15] The inevitable decline of NAD + is being combated through the use of oral supplements of the vitamin B 3 complex such as nicotinamide, nicotinic acid (niacin), nicotinamide mononucleo-tide (NMN), and NR, Figure 1, as well as sirtuin activating compounds like resveratrol. [2,6,8] As companies battle over rights to sell NR exclusively, scientists are exploring the inherent value of the supplement over the analogs previously listed. [16] Niacin was generally used as an NAD + booster until severe flushing and itching caused by the supplement deterred users.…”