2'-deoxy-2',2'-difluoro-NAD+ | 1260238-56-9

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - （5'->5'）-二核苷酸
• 英文名称: 2'-deoxy-2',2'-difluoro-NAD+
• 英文别名: [[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [(2R,3R,5R)-5-(3-carbamoylpyridin-1-ium-1-yl)-4,4-difluoro-3-hydroxyoxolan-2-yl]methyl phosphate
• CAS: 1260238-56-9
• 化学式: C₂₁H₂₅F₂N₇O₁₃P₂
• 分子量: 683.413
• InChiKey: ABNWFPTVZVLTTP-KMZBFTBDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -4.7
• 重原子数：
  45
• 可旋转键数：
  11
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  301
• 氢给体数：
  6
• 氢受体数：
  19

反应信息

• 作为产物：
  描述：

  在 pyrophosphatase 、 yeast nicotinamide mononucleotide adenylyltransferase 1 磷酸三甲酯 、 6-甲基烟酰胺 、 magnesium chloride 、 三氯氧磷 作用下， 反应 3.0h， 生成 2'-deoxy-2',2'-difluoro-NAD+
  参考文献：
  名称：

  [EN] HALOGENATED 2-DEOXY-LACTONES, 2'-DEOXY--NUCLEOSIDES, AND DERIVATIVES THEREOF
  [FR] 2-DÉSOXY-LACTONES HALOGÉNÉES, 2'-DÉSOXY-NUCLÉOSIDES, ET LEURS DÉRIVÉS

  摘要：

  公开号：

  WO2011003018A9

文献信息

• 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.
• [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