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Curr Protoc Nucleic Acid Chem. 2017 Dec 24;71:14.14.1-14.14.9. doi: 10.1002/cpnc.43.

Synthesis of β-Nicotinamide Riboside Using an Efficient Two-Step Methodology.

Author information

1
Department of Pharmacology, Weill Cornell Medical College, New York, New York.

Abstract

A two-step chemical method for the synthesis of β-nicotinamide riboside (NR) is described. NR has achieved wide use as an NAD+ precursor (vitamin B3) and can significantly increase central metabolite NAD+ concentrations in mammalian cells. β-NR can be prepared with an efficient two-step procedure. The synthesis is initiated via coupling of commercially available 1,2,3,5-tetra-O-acetyl-β-D-ribofuranose with ethyl nicotinate in the presence of trimethylsilyl trifluoromethanesulfonate (TMSOTf). 1 H NMR showed that the product was formed with complete stereoselectivity to produce only the β-isomer in high yield (>90% versus starting sugar). The clean stereochemical result suggests that the coupling proceeds via a cationic cis-1,2-acyloxonium-sugar intermediate, which controls addition by nucleophiles to generate predominantly β-stereochemistry. The subsequent deprotection of esters in methanolic ammonia generates the desired product in 85% overall yield versus sugar.

KEYWORDS:

NAD+; nicotinamide riboside; nucleoside synthesis; stereoselective; two-step methodology

PMID:
29275540
PMCID:
PMC5965287
DOI:
10.1002/cpnc.43
[Indexed for MEDLINE]
Free PMC Article

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