1-methylsulfonyl-2-deoxy-2,2-difluoro-3,5-di-O-(triisopropylsilyl)-D-ribofuranose | 1173700-36-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-methylsulfonyl-2-deoxy-2,2-difluoro-3,5-di-O-(triisopropylsilyl)-D-ribofuranose
• 英文别名: 1-O-methylsulfonyl-2-deoxy-2,2-difluoro-3,5-di-O-(triisopropylsilyl)-D-ribofuranose；[(4R,5R)-3,3-difluoro-4-tri(propan-2-yl)silyloxy-5-[tri(propan-2-yl)silyloxymethyl]oxolan-2-yl] methanesulfonate
• CAS: 1173700-36-1
• 化学式: C₂₄H₅₀F₂O₆SSi₂
• 分子量: 560.891
• InChiKey: PAEBMWJYVFJHQN-WELAQSEPSA-N

物化性质

• 沸点：
  517.8±50.0 °C(Predicted)
• 密度：
  1.05±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  7.08
• 重原子数：
  35
• 可旋转键数：
  13
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  79.4
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  1-methylsulfonyl-2-deoxy-2,2-difluoro-3,5-di-O-(triisopropylsilyl)-D-ribofuranose 、 烟酰胺 在 三氟甲磺酸三甲基硅酯 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 生成 1-(2'-deoxy-2',2'-difluoro-3',5'-di-O-(triisopropylsilyl)-ribofuranosyl)-nicotinamide
  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
• 作为产物：
  描述：

  D-(+)-核糖酸-gamma-内酯 在 咪唑 、 二异丁基氢化铝 、 甲基磺酰氯 、 N-氟代双苯磺酰胺 、 三乙胺 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 生成 1-methylsulfonyl-2-deoxy-2,2-difluoro-3,5-di-O-(triisopropylsilyl)-D-ribofuranose
  参考文献：
  名称：

  Efficient Syntheses of Clofarabine and Gemcitabine From 2-Deoxyribonolactone

  摘要：

  The development of a new methodology to achieve electrophilic fluorination of triisopropylsilyl-protected 2-deoxyribonolactone has been employed to synthesize clofarabine and gemcitabine with improved synthetic efficiency versus prior synthetic methods. These studies highlight the versatility of this new methodology to obtain medically relevant 2'-fluoronucleosides.

  DOI：

  10.1080/15257771003597758

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
• Efficient Syntheses of Clofarabine and Gemcitabine From 2-Deoxyribonolactone
  作者：Yana Cen、Anthony A. Sauve

  DOI：10.1080/15257771003597758

  日期：2010.2.26

  The development of a new methodology to achieve electrophilic fluorination of triisopropylsilyl-protected 2-deoxyribonolactone has been employed to synthesize clofarabine and gemcitabine with improved synthetic efficiency versus prior synthetic methods. These studies highlight the versatility of this new methodology to obtain medically relevant 2'-fluoronucleosides.