diethyl <hexyl>phosphinoyl>methyl>phosphonate

• 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 <hexyl>phosphinoyl>methyl>phosphonate
• 英文别名: diethyl ((ethoxy(6-((methylsulfonyl)oxy)hexyl)phosphinoyl)methyl)phosphonate；6-[Diethoxyphosphorylmethyl(ethoxy)phosphoryl]hexyl methanesulfonate
• 化学式: C₁₄H₃₂O₈P₂S
• 分子量: 422.417
• InChiKey: BKBCJMLOJSAXRK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  25
• 可旋转键数：
  16
• 环数：
  0.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  114
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  2-氨基-6-氯嘌呤 、 diethyl <hexyl>phosphinoyl>methyl>phosphonate 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 18.0h， 生成 6-Chloro-9-[6-[diethoxyphosphorylmethyl(ethoxy)phosphoryl]hexyl]purin-2-amine
  参考文献：
  名称：

  [[(Guaninylalkyl)phosphinico]methyl]phosphonic Acids. Multisubstrate Analog Inhibitors of Human Erythrocyte Purine Nucleoside Phosphorylase

  摘要：

  A series of [[(guaninylalkyl)phosphinico]methyl]phosphonic acids, 2, was synthesized and tested as inhibitors of human erythrocyte purine nucleoside phosphorylase (PNPase). The target (phosphinicomethyl)phosphonic acids 2 were synthesized in six or seven steps from alkenylphosphonates 4. The latter were converted to the intermediate alkylmesylates 9 in a series of steps that included (1) conversion of the diethyl phosphonates 4 to the (phosphinoylmethyl)pho sphonates 7 and (2) conversion of the terminal double bond of [(alkenylphosphinoyl)methyl]-phosphonates 7 to the alkylmesylates 9. The pure 9-isomers 2 were obtained by alkylation of 2-amino-6-(2-methoxyethoxy)-9H-purine with alkylmesylates 9 followed by hydrolysis of the protecting groups with concentrated hydrochloric acid and ion exchange chromatography to give 2 as hydrated ammonium salts. The most potent inhibitor of human erythrocyte PNPase, [[[5-(2-amino-1,6-dihydro-6-oxo-9H-purin-9-yl)pentyl]phosphinico]methyl]phosphonic acid(2b), was a multisubstrate analogue inhibitor with a K-i' of 3.1 nM. Optimum PNPase inhibitory activity required the presence of zinc ions in the assay medium. These potent inhibitors of PNPase exhibited only weak activity against human leukemic T-cells in vitro.

  DOI：

  10.1021/jm00006a020
• 作为产物：
  描述：

  甲基磺酰氯 、 diethyl <methyl>phosphonate 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 以100%的产率得到diethyl <hexyl>phosphinoyl>methyl>phosphonate
  参考文献：
  名称：

  [[(Guaninylalkyl)phosphinico]methyl]phosphonic Acids. Multisubstrate Analog Inhibitors of Human Erythrocyte Purine Nucleoside Phosphorylase

  摘要：

  A series of [[(guaninylalkyl)phosphinico]methyl]phosphonic acids, 2, was synthesized and tested as inhibitors of human erythrocyte purine nucleoside phosphorylase (PNPase). The target (phosphinicomethyl)phosphonic acids 2 were synthesized in six or seven steps from alkenylphosphonates 4. The latter were converted to the intermediate alkylmesylates 9 in a series of steps that included (1) conversion of the diethyl phosphonates 4 to the (phosphinoylmethyl)pho sphonates 7 and (2) conversion of the terminal double bond of [(alkenylphosphinoyl)methyl]-phosphonates 7 to the alkylmesylates 9. The pure 9-isomers 2 were obtained by alkylation of 2-amino-6-(2-methoxyethoxy)-9H-purine with alkylmesylates 9 followed by hydrolysis of the protecting groups with concentrated hydrochloric acid and ion exchange chromatography to give 2 as hydrated ammonium salts. The most potent inhibitor of human erythrocyte PNPase, [[[5-(2-amino-1,6-dihydro-6-oxo-9H-purin-9-yl)pentyl]phosphinico]methyl]phosphonic acid(2b), was a multisubstrate analogue inhibitor with a K-i' of 3.1 nM. Optimum PNPase inhibitory activity required the presence of zinc ions in the assay medium. These potent inhibitors of PNPase exhibited only weak activity against human leukemic T-cells in vitro.

  DOI：

  10.1021/jm00006a020

文献信息

• [[(Guaninylalkyl)phosphinico]methyl]phosphonic Acids. Multisubstrate Analog Inhibitors of Human Erythrocyte Purine Nucleoside Phosphorylase
  作者：James L. Kelley、Ed W. McLean、Ronald C. Crouch、Devron R. Averett、Joel V. Tuttle

  DOI：10.1021/jm00006a020

  日期：1995.3

  A series of [[(guaninylalkyl)phosphinico]methyl]phosphonic acids, 2, was synthesized and tested as inhibitors of human erythrocyte purine nucleoside phosphorylase (PNPase). The target (phosphinicomethyl)phosphonic acids 2 were synthesized in six or seven steps from alkenylphosphonates 4. The latter were converted to the intermediate alkylmesylates 9 in a series of steps that included (1) conversion of the diethyl phosphonates 4 to the (phosphinoylmethyl)pho sphonates 7 and (2) conversion of the terminal double bond of [(alkenylphosphinoyl)methyl]-phosphonates 7 to the alkylmesylates 9. The pure 9-isomers 2 were obtained by alkylation of 2-amino-6-(2-methoxyethoxy)-9H-purine with alkylmesylates 9 followed by hydrolysis of the protecting groups with concentrated hydrochloric acid and ion exchange chromatography to give 2 as hydrated ammonium salts. The most potent inhibitor of human erythrocyte PNPase, [[[5-(2-amino-1,6-dihydro-6-oxo-9H-purin-9-yl)pentyl]phosphinico]methyl]phosphonic acid(2b), was a multisubstrate analogue inhibitor with a K-i' of 3.1 nM. Optimum PNPase inhibitory activity required the presence of zinc ions in the assay medium. These potent inhibitors of PNPase exhibited only weak activity against human leukemic T-cells in vitro.