Ning Zhang, Anthony A. Sauve
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引用次数: 8
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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. © 2017 by John Wiley & Sons, Inc.
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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