N,N',N''-tris(dibutylphosphorylmethyl)-1,4,7-triazacyclononane | 137145-67-6

• 分子结构分类: 有机化合物 - 有机酸及其衍生物
• 英文名称: N,N',N''-tris(dibutylphosphorylmethyl)-1,4,7-triazacyclononane
• 英文别名: 1,4,7-Tris(dibutoxyphosphorylmethyl)-1,4,7-triazonane
• CAS: 137145-67-6
• 化学式: C₃₃H₇₂N₃O₉P₃
• 分子量: 747.871
• InChiKey: WKHJUJXLQZUJLQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  48
• 可旋转键数：
  30
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  116
• 氢给体数：
  0
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  N,N',N''-tris(dibutylphosphorylmethyl)-1,4,7-triazacyclononane 在 sodium hydroxide 作用下， 生成 trisodium 1,4,7-triazacyclononane-1,4,7-triyltrimethylene tris(phosphonate monobutyl ester)
  参考文献：
  名称：

  N,N′,N″-tris(methoxymethyl)-1,4,7-triazacyclononane: a new synthetic tool for the synthesis of tris-N-substituted 1,4,7-triazacyclononane derivatives

  摘要：

  描述了N,N′,N′′-三(甲氧基甲基)-1,4,7-三嗪环寡聚烷 (NOTMOM, 2) 的合成，作为一种有用的合成中间体，用于制备一系列新的二烷氧基磷酰甲基、乙氧基(乙基)磷酰甲基和含有1-咪唑基甲基的N,N′,N′′-三取代三嗪环寡聚烷3–8。

  DOI：

  10.1039/c39910001252
• 作为产物：
  描述：

  1,4,7-三氮杂环壬烷 在 sodium 、 N,N-二异丙基乙胺 作用下， 以 苯 为溶剂， 反应 1.0h， 生成 N,N',N''-tris(dibutylphosphorylmethyl)-1,4,7-triazacyclononane
  参考文献：
  名称：

  N,N′,N″-tris(methoxymethyl)-1,4,7-triazacyclononane: a new synthetic tool for the synthesis of tris-N-substituted 1,4,7-triazacyclononane derivatives

  摘要：

  描述了N,N′,N′′-三(甲氧基甲基)-1,4,7-三嗪环寡聚烷 (NOTMOM, 2) 的合成，作为一种有用的合成中间体，用于制备一系列新的二烷氧基磷酰甲基、乙氧基(乙基)磷酰甲基和含有1-咪唑基甲基的N,N′,N′′-三取代三嗪环寡聚烷3–8。

  DOI：

  10.1039/c39910001252

文献信息

• Complexes of cyclic polyaza chelators with cations of alkaline earth metals for enhanced biological activity
  申请人：Winchell S. Harry

  公开号：US20050112066A1

  公开（公告）日：2005-05-26

  Cyclic polyaza chelators that possess high affinity and specificity for first transition series metal cations exhibit an unanticipated improvement in biological activity when administered as complexes with cations of the alkaline earth metals, Ca(II) and Mg(II), most notably Ca(II). By virtue of this improvement, these complexes are particularly effective in the treatment of pathological conditions, including ischemia and ischemia-reperfusion injury.

  具有高亲和力和特异性的环状多氮螯合剂，当与碱土金属阳离子的络合物一起给药时，表现出生物活性的意外改善，其中以Ca(II)和Mg(II)的络合物最为显著，尤其是Ca(II)。由于这种改善，这些络合物在治疗病理条件，包括缺血和缺血再灌注损伤方面特别有效。
• Synthesis of Ester Derivatives of 1,4,7-Triazacyclononane-1,4,7-tris(methylenephosphonic Acid) and 1,4,7-Triazacyclononane-1,4,7-tris(methyleneethylphosphinic Acid)
  作者：István Lázár、A. Dean Sherry

  DOI：10.1055/s-1995-3923

  日期：1995.4

  Two methods have been developed for the synthesis of new 1,4,7-triazacyclononanetris(methylenephosphonic acid) (3-6, 8-11) and -tris(methyleneethylphosphinic acid) (7, 12) ester derivatives. The first procedure includes the synthesis of 2 in anhydrous THF which can then be used as a useful synthetic intermediate for several new derivatives of 1,4,7-triazacyclononane (1). In the second procedure, compound 1 and dialkyl phosphite or ethyl ethylphosphinate are reacted with paraformaldehyde in refluxing benzene yielding the corresponding esters in good to excellent yield. New macrocyclic complexing agents 8-12 have been prepared by either basic (8-11) or acidic (12) hydrolysis of the corresponding ester derivatives, or directly from the starting macrocycle 12. Side reactions decreasing the yield and purity of the products are also discussed.

  开发了两种合成新的1,4,7-三氮杂环壬烯三（亚甲基膦酸）(3-6, 8-11)和三（亚甲基乙基膦酸）(7, 12)酯衍生物的方法。第一种方法包括在无水THF中合成化合物2，该化合物可以作为几种新的1,4,7-三氮杂环壬烯（1）衍生物的有用合成中间体。在第二种方法中，化合物1与二烷基膦酸酯或乙基乙基膦酸酯在回流苯中与聚甲醛反应，得到了相应的酯，产率良好至优异。新型宏环络合剂8-12通过相应酯衍生物的碱性（8-11）或酸性（12）水解，或直接从起始宏环12制备而成。还讨论了减少产物产率和纯度的副反应。
• Co-ordination chemistry and molecular mechanics study of the magnesium(II) and calcium(II) complexes of trisubstituted 1,4,7-triazacyclononane derivatives
  作者：Jurriaan Huskens、A. Dean Sherry

  DOI：10.1039/a703640j

  日期：——

  The affinities of 1,4,7-tris(2-hydroxyalkyl)-1,4,7-triazacyclononane derivatives for MgII and CaII were found to differ greatly. Whereas 1,4,7-tris(2-hydroxyethyl)- (L1), 1,4,7-tris(2-hydroxy-2-methylpropyl)- (L2) and the unsymmetrical 1,4,7-tris(2-hydroxypropyl)-1,4,7-triazacyclononane derivative L3b barely discriminated between MgII and CaII, the symmetrical isomer L3a was more than 500 times more selective for MgII than for CaII. Similar selectivity differences were observed between the diastereomers of 1,4,7-tris(2-hydroxy-2-phenylethyl)- (L4) and 1,4,7-tris(2-hydroxydodecyl)-1,4,7-triazacyclononane (L5). These selectivities were related to the structure of the magnesium complexes as shown by molecular mechanics (MMX) calculations. Only those ligands favoring the formation of a magnesium complex with a large twist angle between the planes of co-ordinating oxygens and ring nitrogens resulting in a small, tight cavity showed a large preference for MgII over CaII. The MMX calculations predicted large twist angle structures for phosphinate derivatives, and for a phosphonate monoester derivative, and these ligands were found to have a high selectivity for MgII. Similarly, the calculated preference for the smaller twist angle correctly predicted the lack of MgII/CaII selectivity for acetate and amide derivatives and for a phosphonate diester derivative. Equilibration of the complexes of the ligands in the presence of both MgII and CaII was slow, as shown for example by kd,0 = 2.1 × 10–4 s–1 for CaL3a. These dissociation rates were a factor of 100 times larger at the boundary of a two-phase (water–chloroform) system.

  发现1,4,7-三(2-羟烷基)-1,4,7-三氮杂环壬烷衍生物对MgII和CaII的亲和力差异很大。而 1,4,7-三(2-羟乙基)- (L1)、1,4,7-三(2-羟基-2-甲基丙基)-(L2) 和不对称 1,4,7-三(2 (羟丙基)-1,4,7-三氮杂环壬烷衍生物L3b几乎无法区分MgII和CaII，对称异构体L3a对MgII的选择性比对CaII的选择性高500倍以上。在 1,4,7-三(2-羟基-2-苯基乙基)-(L4) 和 1,4,7-三(2-羟基十二烷基)-1,4,7-三氮杂环壬烷的非对映异构体之间观察到类似的选择性差异（L5）。正如分子力学 (MMX) 计算所示，这些选择性与镁络合物的结构有关。只有那些有利于形成镁配合物的配体，该配合物在配位氧和环氮平面之间具有大扭转角，从而形成小而紧密的空腔，才显示出对 MgII 的优先选择超过 CaII。 MMX 计算预测了次膦酸酯衍生物和膦酸酯单酯衍生物的大扭转角结构，并且发现这些配体对 MgII 具有高选择性。类似地，计算出的对较小扭转角的偏好正确地预测了 MgII/CaII 对乙酸酯和酰胺衍生物以及膦酸酯二酯衍生物缺乏选择性。在 MgII 和 CaII 存在的情况下，配体复合物的平衡很慢，如 CaL3a 的 kd,0 = 2.1 × 10–4 s–1 所示。在两相（水-氯仿）系统的边界处，这些解离速率是原来的 100 倍。