diethyl 1,1-difluoro-2-(3-methylidenetetrahydro-2H-pyran-4-yl)ethylphosphonate | 318271-54-4

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机膦酸及其衍生物
• 英文名称: diethyl 1,1-difluoro-2-(3-methylidenetetrahydro-2H-pyran-4-yl)ethylphosphonate
• 英文别名: 4-[2-[Diethoxy(oxido)phosphaniumyl]-2,2-difluoroethyl]-3-methylideneoxane；4-[2-[diethoxy(oxido)phosphaniumyl]-2,2-difluoroethyl]-3-methylideneoxane
• CAS: 318271-54-4
• 化学式: C₁₂H₂₁F₂O₄P
• 分子量: 298.267
• InChiKey: NWQFEMPORQYGDM-UHFFFAOYSA-N

物化性质

• 沸点：
  340.5±42.0 °C(Predicted)
• 密度：
  1.15±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  19
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  50.8
• 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-(3-methylidenetetrahydro-2H-pyran-4-yl)ethylphosphonate 在 三甲基溴硅烷 、 硼烷 、 双氧水 、 sodium acetate 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 12.0h， 生成 1,1-difluoro-2-{(3S^*,4S^*)-3-[(6-oxo-1,6-dihydro-9H-purin-9-yl)methyl]tetrahydro-2H-pyran-4-yl}ethylphosphonic acid
  参考文献：
  名称：

  Synthesis and evaluation of multisubstrate analogue inhibitors of purine nucleoside phosphorylases

  摘要：

  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.

  DOI：

  10.1016/s0968-0896(00)00192-9
• 作为产物：
  描述：

  bromozinc(1+),1-[difluoromethyl(ethoxy)phosphoryl]oxyethane 在 偶氮二异丁腈 、 三正丁基氢锡 、 copper(I) bromide 作用下， 以 N,N-二甲基乙酰胺 、 甲苯 为溶剂， 反应 10.0h， 生成 diethyl 1,1-difluoro-2-(3-methylidenetetrahydro-2H-pyran-4-yl)ethylphosphonate
  参考文献：
  名称：

  Synthesis and evaluation of multisubstrate analogue inhibitors of purine nucleoside phosphorylases

  摘要：

  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.

  DOI：

  10.1016/s0968-0896(00)00192-9

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.