(Z)-4-[(diisopropylphosphono)methoxy]-1-triphenylmethoxy-2-butene | 265322-90-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: (Z)-4-[(diisopropylphosphono)methoxy]-1-triphenylmethoxy-2-butene
• 英文别名: [[(Z)-4-[di(propan-2-yloxy)phosphorylmethoxy]but-2-enoxy]-diphenylmethyl]benzene
• CAS: 265322-90-5
• 化学式: C₃₀H₃₇O₅P
• 分子量: 508.595
• InChiKey: SPNYJVZSILANKW-PFONDFGASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.9
• 重原子数：
  36
• 可旋转键数：
  14
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  54
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (Z)-4-[(diisopropylphosphono)methoxy]-1-triphenylmethoxy-2-butene 在 80percent aq. AcOH 作用下， 反应 0.33h， 以96%的产率得到(Z)-4-[(diisopropylphosphono)methoxy]-2-buten-1-ol
  参考文献：
  名称：

  Design, Synthesis, and Enzymatic Evaluation of Multisubstrate Analogue Inhibitors of Escherichia coli Thymidine Phosphorylase

  摘要：

  A series of acyclic phosphonate derivatives of thymine has been synthesized and tested as multisubstrate analogue inhibitors of Escherichia colt thymidine phosphorylase. The compounds synthesized include 1-(phosphonoalkyl)thymines with six to nine methylenes (1-4, respectively); 1-[(Z)-4-phosphonomethoxy-2-butenyl]thymine (5) and its butyl and 2,3-cis-dihydroxybutyl derivatives (6 and 7, respectively); 1-[(Z)-(4-(phosphonomethoxy)methoxy)-2-butenyl]thymine (8) and also its butyl and 2,3-cis-dihydroxybutyl analogues (9 and 10); and 1-[((Z)-4-(phosphonomethoxy)-2-butenoxy)methyl]thymine(11), Evaluation of these compounds against E. coli revealed significant enzymatic inhibition by 2, 3, 4, 6, and 8 at a concentration of 1000 mu M, 3 and 4 being the most potent. Replacement of the thymine base in 3 by 6-amino-5-bromouracil and 7-deazaxanthine afforded compounds 12 and 13, which showed a pronounced improvement of TPase inhibition, comparable to 7-deazaxanthine. When inorganic phosphate was used as a variable substrate, compounds 12 and 13 displayed competitive kinetics with respect to phosphate, indicating a direct interaction of these compounds with the phosphate binding site. Also compounds 12 and 13 were found to be competitive inhibitors of TPase against thymidine as a variable substrate. These results are consistent with the compounds being multisubstrate analogue inhibitors of E. coli TPase, and they represent the first example of such TPase inhibitors.

  DOI：

  10.1021/jm9911377
• 作为产物：
  描述：

  (二异丙氧基磷酰)甲基对甲苯磺酸酯 、 (Z)-4-(trityloxy)but-2-en-1-ol 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以43%的产率得到(Z)-4-[(diisopropylphosphono)methoxy]-1-triphenylmethoxy-2-butene
  参考文献：
  名称：

  Design, Synthesis, and Enzymatic Evaluation of Multisubstrate Analogue Inhibitors of Escherichia coli Thymidine Phosphorylase

  摘要：

  A series of acyclic phosphonate derivatives of thymine has been synthesized and tested as multisubstrate analogue inhibitors of Escherichia colt thymidine phosphorylase. The compounds synthesized include 1-(phosphonoalkyl)thymines with six to nine methylenes (1-4, respectively); 1-[(Z)-4-phosphonomethoxy-2-butenyl]thymine (5) and its butyl and 2,3-cis-dihydroxybutyl derivatives (6 and 7, respectively); 1-[(Z)-(4-(phosphonomethoxy)methoxy)-2-butenyl]thymine (8) and also its butyl and 2,3-cis-dihydroxybutyl analogues (9 and 10); and 1-[((Z)-4-(phosphonomethoxy)-2-butenoxy)methyl]thymine(11), Evaluation of these compounds against E. coli revealed significant enzymatic inhibition by 2, 3, 4, 6, and 8 at a concentration of 1000 mu M, 3 and 4 being the most potent. Replacement of the thymine base in 3 by 6-amino-5-bromouracil and 7-deazaxanthine afforded compounds 12 and 13, which showed a pronounced improvement of TPase inhibition, comparable to 7-deazaxanthine. When inorganic phosphate was used as a variable substrate, compounds 12 and 13 displayed competitive kinetics with respect to phosphate, indicating a direct interaction of these compounds with the phosphate binding site. Also compounds 12 and 13 were found to be competitive inhibitors of TPase against thymidine as a variable substrate. These results are consistent with the compounds being multisubstrate analogue inhibitors of E. coli TPase, and they represent the first example of such TPase inhibitors.

  DOI：

  10.1021/jm9911377

文献信息

• Design, Synthesis, and Enzymatic Evaluation of Multisubstrate Analogue Inhibitors of <i>Escherichia </i><i>coli</i> Thymidine Phosphorylase
  作者：Antonio Esteban-Gamboa、Jan Balzarini、Robert Esnouf、Erik De Clercq、María-José Camarasa、María-Jesús Pérez-Pérez

  DOI：10.1021/jm9911377

  日期：2000.3.1

  A series of acyclic phosphonate derivatives of thymine has been synthesized and tested as multisubstrate analogue inhibitors of Escherichia colt thymidine phosphorylase. The compounds synthesized include 1-(phosphonoalkyl)thymines with six to nine methylenes (1-4, respectively); 1-[(Z)-4-phosphonomethoxy-2-butenyl]thymine (5) and its butyl and 2,3-cis-dihydroxybutyl derivatives (6 and 7, respectively); 1-[(Z)-(4-(phosphonomethoxy)methoxy)-2-butenyl]thymine (8) and also its butyl and 2,3-cis-dihydroxybutyl analogues (9 and 10); and 1-[((Z)-4-(phosphonomethoxy)-2-butenoxy)methyl]thymine(11), Evaluation of these compounds against E. coli revealed significant enzymatic inhibition by 2, 3, 4, 6, and 8 at a concentration of 1000 mu M, 3 and 4 being the most potent. Replacement of the thymine base in 3 by 6-amino-5-bromouracil and 7-deazaxanthine afforded compounds 12 and 13, which showed a pronounced improvement of TPase inhibition, comparable to 7-deazaxanthine. When inorganic phosphate was used as a variable substrate, compounds 12 and 13 displayed competitive kinetics with respect to phosphate, indicating a direct interaction of these compounds with the phosphate binding site. Also compounds 12 and 13 were found to be competitive inhibitors of TPase against thymidine as a variable substrate. These results are consistent with the compounds being multisubstrate analogue inhibitors of E. coli TPase, and they represent the first example of such TPase inhibitors.