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

Q4 Chemistry
Ning Zhang, Anthony A. Sauve
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引用次数: 8

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). 1H 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. © 2017 by John Wiley & Sons, Inc.

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高效两步法合成β-烟酰胺核苷
介绍了两步法合成β-烟酰胺核苷(NR)的方法。NR已被广泛用作NAD+前体(维生素B3),并能显著增加哺乳动物细胞中中枢代谢物NAD+的浓度。β-NR可通过两步法高效制备。该合成是通过在三甲基硅基三氟甲烷磺酸盐(TMSOTf)存在下,将市售的1,2,3,5-四- o -乙酰基-β- d -核呋喃糖与烟酸乙酯偶联而开始的。1H NMR表明产物形成具有完全立体选择性,仅生成β-异构体,产率高(与起始糖相比为90%)。干净的立体化学结果表明,偶联是通过阳离子顺式-1,2-丙氧基糖中间体进行的,该中间体控制亲核试剂的加成,主要产生β-立体化学。随后酯在甲醇氨中的脱保护产生所需的产品,与糖相比,总收率为85%。©2017 by John Wiley &儿子,Inc。
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来源期刊
Current Protocols in Nucleic Acid Chemistry
Current Protocols in Nucleic Acid Chemistry Chemistry-Organic Chemistry
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期刊介绍: Published in association with International Society for Nucleosides, Nucleotides & Nucleic Acids (IS3NA) , Current Protocols in Nucleic Acid Chemistry is equally valuable for biotech, pharmaceutical, and academic labs. It is the resource for designing and running successful research projects in the rapidly growing and changing field of nucleic acid, nucleotide, and nucleoside research.
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