Syntheses of nicotinamide riboside and derivatives: effective agents for increasing nicotinamide adenine dinucleotide concentrations in mammalian cells.
A new two-step methodology achieves stereoselective synthesis of beta-nicotinamide riboside and a series of related amide, ester, and acid nucleosides. Compounds were prepared through a triacetylated-nicotinate ester nucleoside, via coupling of either ethylnicotinate or phenylnicotinate with 1,2,3,5-tetra-O-acetyl-beta-D-ribofuranose. Nicotinamide riboside, nicotinic acid riboside, O-ethylnicotinate riboside, O-methylnicotinate riboside, and several N-alkyl derivatives increased NAD+ concentrations from 1.2-2.7-fold in several mammalian cell lines. These findings establish bioavailability and potent effects of these nucleosides in stimulating the increase of NAD+ concentrations in mammalian cells.
Department of Pharmacology, Weill Medical College of Cornell University, Manhattan, NY 10021, USA.
Tianle
T
Yang
Noel Yan-Ki
NY
Chan
Anthony A
AA
Sauve
D000818:Animals; D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004952:Esters; D006801:Humans; D051379:Mice; D009243:NAD / Q000378:metabolism*; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D009705:Nucleosides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D011726:Pyridinium Compounds; D013329:Structure-Activity Relationship
D004952:Esters; D009705:Nucleosides; D011726:Pyridinium Compounds; C018613:nicotinamide-beta-riboside; D009243:NAD; D009536:Niacinamide