3-carbamoyl-1-((2R,3S,4R,5R)-3-fluoro-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2yl)pyridin-1-ium | 135339-76-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 3-carbamoyl-1-((2R,3S,4R,5R)-3-fluoro-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2yl)pyridin-1-ium
• 英文别名: β-1-(2'-deoxy-2'-fluoroarabinofuranosyl)nicotinamide；2'-deoxy-2'-fluoro-β-D-arabinofuranosylnicotinamide；nicotinamide 2'-fluoro-β-D-arabinofuranoside；1-(2'-deoxy-2'-fluoro-arabinofuranosyl)-nicotinamide；3-Carbamoyl-1-((2R,3S,4R,5R)-3-fluoro-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)pyridin-1-ium；1-[(2R,3S,4R,5R)-3-fluoro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]pyridin-1-ium-3-carboxamide
• CAS: 135339-76-3
• 化学式: C₁₁H₁₄FN₂O₄
• 分子量: 257.242
• InChiKey: LFSMVVIWPMLCQU-PKIKSRDPSA-O

计算性质

• 辛醇/水分配系数(LogP)：
  -0.7
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  96.7
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-carbamoyl-1-((2R,3S,4R,5R)-3-fluoro-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2yl)pyridin-1-ium 在 potassium chloride 作用下， 生成 2-fluoro-2-deoxy-D-arabinose
  参考文献：
  名称：

  Substituent effects on the pH-independent hydrolysis of 2'-substituted nicotinamide arabinosides

  摘要：

  The rates of the pH-independent hydrolysis of a series of 2'-substituted nicotinamide arabinosides have been measured and are used to analyze the direct inductive substituent effect on the stability of oxocarbocationic intermediates.

  DOI：

  10.1021/jo00017a004
• 作为产物：
  描述：

  2-deoxy-2-fluoro-3,5-di-O-benzoyl-D-arabinofuranosyl bromide 在 甲醇 、 potassium carbonate 作用下， 以 乙腈 为溶剂， 生成 3-carbamoyl-1-((2R,3S,4R,5R)-3-fluoro-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2yl)pyridin-1-ium
  参考文献：
  名称：

  使用细胞渗透性、基于机制的荧光小分子探针揭示 CD38 细胞定位

  摘要：

  烟酰胺腺嘌呤二核苷酸 (NAD) 越来越被认为是影响众多生物途径的重要信号分子。因此，代谢 NAD 的酶具有重要的生物学功能。哺乳动物中的一种 NAD 代谢酶是 CD38，这是一种 II 型跨膜蛋白，可将 NAD 主要转化为二磷酸腺苷核糖 (ADPR) 和少量环二磷酸腺苷核糖 (cADPR)。CD38 的定位最初被认为仅在质膜上，但后来的报告显示重要的或仅是细胞内 CD38。凭借高效的 NAD 水解活性，细胞内 CD38 可能导致细胞 NAD 的消耗，从而产生有害影响。因此，CD38 的细胞内定位需要仔细验证。这里，我们报告了一种可渗透细胞的荧光小分子 (SR101–F-araNMN) 的合成和应用，该分子可以共价标记具有酶活性的 CD38，同时对活细胞的干扰最小。使用这种荧光探针，我们发现 CD38 主要位于 Raji 和视黄酸 (RA) 处理的 HL-60 细胞的质膜上。此外，该探针显示

  DOI：

  10.1021/ja411046j

文献信息

• Studies on the Synthesis of Nicotinamide Nucleoside and Nucleotide Analogues and Their Inhibitions towards CD38 NADase
  作者：Liangren Zhang、Anna Ka Yee Kwong、Zhenjun Yang、Zhe Chen、Hon Cheung Lee、Lihe Zhang

  DOI：10.3987/com-11-12361

  日期：——

  Nicotinamide adenine dinucleotide (NAD) analogues inhibit the NADase activity of CD38. In the current study, efficient protocols for the synthesis of substituted-nicotinamide nucleosides and nucleotides were developed. The one-pot phosphorylation esterification strategy provides a convenient way of obtaining nicotinamide nucleoside phosphodiesters from the corresponding nucleosides. Structure activity relationship information revealed that replacement of 3'-hydroxy group with F or N-3 led to the considerably decrease of activity as compared with ara-F NMN. Phosphodiesterification of nicotinamide nucleosides lowers their inhibitory activities in some extent.
• [EN] HALOGENATED 2-DEOXY-LACTONES, 2'-DEOXY--NUCLEOSIDES, AND DERIVATIVES THEREOF<br/>[FR] 2-DÉSOXY-LACTONES HALOGÉNÉES, 2'-DÉSOXY-NUCLÉOSIDES, ET LEURS DÉRIVÉS
  申请人：UNIV CORNELL

  公开号：WO2011003018A9

  公开（公告）日：2012-11-08
• Diastereocontrolled Electrophilic Fluorinations of 2-Deoxyribonolactone: Syntheses of All Corresponding 2-Deoxy-2-fluorolactones and 2′-Deoxy-2′-fluoro-NAD⁺s
  作者：Yana Cen、Anthony A. Sauve

  DOI：10.1021/jo900637f

  日期：2009.8.21

  Methods to construct 2'-deoxy-2'-fluoro nucleosides have undergone limited improvement in the last 20 years in spite of the substantially increased value of these compounds as pharmaceuticals and as tools for studying biological processes. We herein describe a consolidated approach to synthesize precursors to these commercially and scientifically valuable compounds via diastereocontrolled fluorination of the readily available precursor 2-deoxy-D-ribonolactone. With employment of appropriate sterically bulky silyl protecting groups at the 3 and 5 positions, controlled electrophilic fluorination of the Li-ribonolactone enolate by N-fluorodibenzenesulfonamide yielded the corresponding 2-deoxy-2-fluoroarabinolactone in high isolated yield (72%) The protected 2-deoxy-2,2-difluororibonolactone was obtained similarly in high yield from a second round of electrophilic fluorination (two steps, 51% from protected ribonolactone starting material). Accomplishment of the difficult ribofluorination of the lactone was achieved by the directive effects of a diastereoselectively installed (x-trimethylsilyl group. Electrophilic fluorination of a protected 2-deoxy-2-trimethylsilylarabinolactone via enolate generation provided the protected 2-deoxy-2-fluororibolactone as the exclusive fluorinated product. The reaction also yielded the starting material, the desilylated protected 2-deoxyribonolactone, which was recycled to provide a 38% chemical yield of the fluorinated product (versus initial protected ribonolactone),after consecutive silylation and fluorination cycles. Using our fluorinated sugar precursors, we prepared the 2'-fluoroarabino-, 2'-fluororibo-, and 2',2'-difluoronicotinamide adenine dinucleotides (NAD(+)) of potential biological interest. These syntheses provide the most consolidated and efficient methods for production of sugar precursors of 2'-deoxy-2'-fluoronucleosides and have the advantage of utilizing an air-stable electrophilic fluorinating agent. The fluorinated NAD(+)s are anticipated to be useful for studying a variety of cellular metabolic and signaling processes.
• Revealing CD38 Cellular Localization Using a Cell Permeable, Mechanism-Based Fluorescent Small-Molecule Probe
  作者：Jonathan H. Shrimp、Jing Hu、Min Dong、Brian S. Wang、Robert MacDonald、Hong Jiang、Quan Hao、Andrew Yen、Hening Lin

  DOI：10.1021/ja411046j

  日期：2014.4.16

  the synthesis and application of a cell permeable, fluorescent small molecule (SR101–F-araNMN) that can covalently label enzymatically active CD38 with minimal perturbation of live cells. Using this fluorescent probe, we revealed that CD38 is predominately on the plasma membrane of Raji and retinoic acid (RA)-treated HL-60 cells. Additionally, the probe revealed no CD38 expression in K562 cells, which

  烟酰胺腺嘌呤二核苷酸 (NAD) 越来越被认为是影响众多生物途径的重要信号分子。因此，代谢 NAD 的酶具有重要的生物学功能。哺乳动物中的一种 NAD 代谢酶是 CD38，这是一种 II 型跨膜蛋白，可将 NAD 主要转化为二磷酸腺苷核糖 (ADPR) 和少量环二磷酸腺苷核糖 (cADPR)。CD38 的定位最初被认为仅在质膜上，但后来的报告显示重要的或仅是细胞内 CD38。凭借高效的 NAD 水解活性，细胞内 CD38 可能导致细胞 NAD 的消耗，从而产生有害影响。因此，CD38 的细胞内定位需要仔细验证。这里，我们报告了一种可渗透细胞的荧光小分子 (SR101–F-araNMN) 的合成和应用，该分子可以共价标记具有酶活性的 CD38，同时对活细胞的干扰最小。使用这种荧光探针，我们发现 CD38 主要位于 Raji 和视黄酸 (RA) 处理的 HL-60 细胞的质膜上。此外，该探针显示
• Substituent effects on the pH-independent hydrolysis of 2'-substituted nicotinamide arabinosides
  作者：Anthony L. Handlon、Norman J. Oppenheimer

  DOI：10.1021/jo00017a004

  日期：1991.8

  The rates of the pH-independent hydrolysis of a series of 2'-substituted nicotinamide arabinosides have been measured and are used to analyze the direct inductive substituent effect on the stability of oxocarbocationic intermediates.