diethyl [1,1-difluoro-2-(4-methylenetetrahydro-3-furanyl)ethyl]phosphonate | 251345-40-1

• 分子结构分类: 有机化合物 - 有机酸及其衍生物
• 英文名称: diethyl [1,1-difluoro-2-(4-methylenetetrahydro-3-furanyl)ethyl]phosphonate
• 英文别名: 3-(2-Diethoxyphosphoryl-2,2-difluoroethyl)-4-methylideneoxolane
• CAS: 251345-40-1
• 化学式: C₁₁H₁₉F₂O₄P
• 分子量: 284.24
• InChiKey: WXPGVFMZIRDBEU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  18
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  44.8
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  diethyl [1,1-difluoro-2-(4-methylenetetrahydro-3-furanyl)ethyl]phosphonate 在 dimethyl sulfide borane 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 为溶剂， 生成 diethyl 2-{(3S^*,4S^*)-4-[(6-chloro-9H-purin-9-yl)methyl]tetrahydro-3-furanyl}-1,1-difluoroethylphosphonate
  参考文献：
  名称：

  Synthesis and biological evaluation of 1,1-difluoro-2-(tetrahydro-3-furanyl)ethylphosphonic acids possessing a N9-purinylmethyl functional group at the ring. A new class of inhibitors for purine nucleoside phosphorylases

  摘要：

  1,1-Difluaro-2-(tetrahydro-3-furanyl)ethylphosphonic acids cis-3 and trans-3 possessing a N9-purinylmethyl functionality at the ring were synthesized and tested as "multi-substrate analogue" inhibitors for purine nucleoside phosphorylases. Radical cyclization of allyic alpha,alpha-difluorophosphonate (E)-7 was applied to construct the alpha,alpha-difluorophosphonate-functionalized tetrahydrofuranyl moiety. The IC50 values of cis-3 and trans-3 for human erythrocyte PNP-catalyzed phosphorylation of inosine were determined to be 88 and 320 nM, respectively. The stereochemistry of the inhibitors was found to affect significantly the inhibitory potency. (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(99)00495-3
• 作为产物：
  描述：

  (E)-3-[(2-bromoallyl)oxy]-1-iodo-1-propene 在 三乙基硼 、 三正丁基氢锡 、 copper(I) bromide 作用下， 以 四氢呋喃 、 N,N-二甲基乙酰胺 为溶剂， 反应 0.17h， 生成 diethyl [1,1-difluoro-2-(4-methylenetetrahydro-3-furanyl)ethyl]phosphonate
  参考文献：
  名称：

  Synthesis and biological evaluation of 1,1-difluoro-2-(tetrahydro-3-furanyl)ethylphosphonic acids possessing a N9-purinylmethyl functional group at the ring. A new class of inhibitors for purine nucleoside phosphorylases

  摘要：

  1,1-Difluaro-2-(tetrahydro-3-furanyl)ethylphosphonic acids cis-3 and trans-3 possessing a N9-purinylmethyl functionality at the ring were synthesized and tested as "multi-substrate analogue" inhibitors for purine nucleoside phosphorylases. Radical cyclization of allyic alpha,alpha-difluorophosphonate (E)-7 was applied to construct the alpha,alpha-difluorophosphonate-functionalized tetrahydrofuranyl moiety. The IC50 values of cis-3 and trans-3 for human erythrocyte PNP-catalyzed phosphorylation of inosine were determined to be 88 and 320 nM, respectively. The stereochemistry of the inhibitors was found to affect significantly the inhibitory potency. (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(99)00495-3

文献信息

• Synthesis and evaluation of multisubstrate analogue inhibitors of purine nucleoside phosphorylases
  作者：Tsutomu Yokomatsu、Yoshinobu Hayakawa、Taro Kihara、Satoru Koyanagi、Shinji Soeda、Hiroshi Shimeno、Shiroshi Shibuya

  DOI：10.1016/s0968-0896(00)00192-9

  日期：2000.11

  1,1-Difluoro-2-(tetrahydro-3-furanly)ethylphosphonic acids (+/-)-cis-4a and (+/-)-trans-4a possessing a (purine-9-yl)methyl functionality at the ring as well as their homologues (+)-cis-4b and (+)-trans-4b were synthesized and tested as 'multi-substrate analogue' inhibitors for purine nucleoside phosphorylases. Radical cyclization of allylic alpha,alpha -difluorophosphonates 8a,b was applied to construct the alpha,alpha -difluorophosphonate-functionalized oxacycles 9a,b. The IC50 values of the nucleo tide analogues (+/-)-cis-4a and (+/-)-cis-4b were 88 and 38 nM, respectively, for human erythrocyte PNP-catalyzed phosphorylation of inosine in the presence of 100 mM orthophosphate. The stereochemistry of the inhibitors was found to affect significantly the inhibitory potency. The transisomers (+/-)-trans-4a and (+/-)-trans4b were ca. 4-fold less potent than the corresponding cis-isomers. At an intracellular concentration of orthophosphate (1 mM), (+/-)-cis-4b, the most potent compound of this series, was shown to have IC50 and K-i values of 8.7 and 3.5 nM, respectively. (C) 2000 Elsevier Science Ltd. All rights reserved.