19132-12-8Relevant articles and documents
Dihydronicotinamide riboside is a potent NAD concentration enhancer in vitro and in vivo
Yang, Yue,Mohammed, Farheen Sultana,Zhang, Ning,Sauve, Anthony A.
, p. 9295 - 9307 (2019)
Interest in pharmacological agents capable of increasing cellular NAD concentrations has stimulated investigations of nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN). NR and NMN require large dosages for effect. Herein, we describe synthesis of dihydronicotinamide riboside (NRH) and the discovery that NRH is a potent NAD concentration-enhancing agent, which acts within as little as 1 h after administration to mammalian cells to increase NAD concentrations by 2.5–10-fold over control values. Comparisons with NR and NMN show that in every instance, NRH provides greater NAD increases at equivalent concentrations. NRH also provides substantial NAD increases in tissues when administered by intraperitoneal injection to C57BL/6J mice. NRH substantially increases NAD/NADH ratio in cultured cells and in liver and no induction of apoptotic markers or significant increases in lactate levels in cells. Cells treated with NRH are resistant to cell death caused by NAD-depleting genotoxins such as hydrogen peroxide and methylmethane sulfonate. Studies to identify its biochemical mechanism of action showed that it does not inhibit NAD consumption, suggesting that it acts as a biochemical precursor to NAD. Cell lysates possess an ATP-dependent kinase activity that efficiently converts NRH to the compound NMNH, but independent of Nrk1 or Nrk2. These studies identify a putative new metabolic pathway to NAD and a potent pharmacologic agent for NAD concentration enhancement in cells and tissues.
Dihydronicotinamide riboside: synthesis from nicotinamide riboside chloride, purification and stability studies
Abbaspourrad, Alireza,Enayati, Mojtaba,Khazdooz, Leila,Madarshahian, Sara,Ufheil, Gerhard,Wooster, Timothy J.,Zarei, Amin
, p. 21036 - 21047 (2021/07/01)
In the present work, we describe an efficient method for scalable synthesis and purification of 1,4-dihydronicotinamide riboside (NRH) from commercially available nicotinamide riboside chloride (NRCl) and in the presence of sodium dithionate as a reducing agent. NRH is industrially relevant as the most effective, synthetic NAD+precursor. We demonstrated that solid phase synthesis cannot be used for the reduction of NRCl to NRH in high yield, whereas a reduction reaction in water at room temperature under anaerobic conditions is shown to be very effective, reaching a 55% isolation yield. For the first time, by using common column chromatography, we were able to highly purify this sensitive bio-compound with good yield. A series of identifications and analyses including HPLC, NMR, LC-MS, FTIR, and UV-vis spectroscopy were performed on the purified sample, confirming the structure of NRH as well as its purity to be 96%. Thermal analysis of NRH showed higher thermal stability compared to NRCl, and with two major weight losses, one at 218 °C and another at 805 °C. We also investigated the long term stability effects of temperature, pH, light, and oxygen (as air) on the NRH in aqueous solutions. Our results show that NRH can be oxidized in the presence of oxygen, and it hydrolyzed quickly in acidic conditions. It was also found that the degradation rate is lower under a N2atmosphere, at lower temperatures, and under basic pH conditions.
Preparation method of nicotinamide ribose, reduction state and salt of nicotinamide ribose
-
, (2020/11/10)
The invention belongs to the technical field of organic synthesis. The invention discloses a preparation method of nicotinamide ribose. The method comprises the following steps: reacting an intermediate A with nicotinamide in the presence of TMSOTf to obt
