2R,3R,8R,9R-bis(cyclohexano)-1,4,7,10,13-pentaazacyclopentadecane | 160884-81-1

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 2R,3R,8R,9R-bis(cyclohexano)-1,4,7,10,13-pentaazacyclopentadecane
• 英文别名: 2R,3R,8S,9S-dicyclohexano-1,4,7,10,13-pentaazacyclopentadecane；2R,3R,8R,9R-dicyclohexano-1,4,7,10,13-pentaazacyclopentadecane；(1R,6R,11R,19R)-2,5,12,15,18-pentazatricyclo[17.4.0.06,11]tricosane
• CAS: 160884-81-1
• 化学式: C₁₈H₃₇N₅
• 分子量: 323.525
• InChiKey: VKFZMVMKZOTZJT-BRSBDYLESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  23
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  60.2
• 氢给体数：
  5
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2R,3R,8R,9R-bis(cyclohexano)-1,4,7,10,13-pentaazacyclopentadecane 、 manganese(ll) chloride 以 甲醇 为溶剂， 生成 dichloro(2R,3R,8R,9R-bis(cyclohexano)-1,4,7,10,13-pentaazacyclopentadecane)manganese(II)
  参考文献：
  名称：

  Riley, Dennis P.; Henke, Susan L.; Lennon, Patrick J., Inorganic Chemistry, 1999, vol. 38, # 8, p. 1908 - 1917

  摘要：

  DOI：
• 作为产物：
  描述：

  在 氢氧化钾 、 lithium aluminium tetrahydride 、 TEA 、 二苯基磷酸 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 2R,3R,8R,9R-bis(cyclohexano)-1,4,7,10,13-pentaazacyclopentadecane
  参考文献：
  名称：

  Pseudopeptide synthesis of a pentaazamacrocycle containing two trans-fused cyclohexane rings

  摘要：

  The synthesis of a bis-cyclohexyl-fused pentaazamacrocycle via head-to-tail pseudopeptide cyclization chemistry is described. The bis-cyclohexyl-fused cyclic pseudopeptide 11 displays intramolecular hydrogen bonding which has been characterized by variable temperature NMR spectroscopy and X-Ray Crystallography. (C) 1997 Elsevier Science Ltd.

  DOI：

  10.1016/s0040-4039(97)00563-7

文献信息

• New conformationally constrained polyaza macrocycles prepared via the bis(chloroacetamide) method
  作者：Patrick J. Lennon、Hayat Rahman、Karl W. Aston、Susan L. Henke、Dennis P. Riley

  DOI：10.1016/s0040-4039(00)75981-8

  日期：1994.1

  The synthesis of two new series of conformationally constrained polyazamacrocycles featuring polysubstitution at macrocycle ring carbons is described.

  描述了两个新的一系列构象受限的聚氮杂大环化合物的合成，其特征是在大环环碳上具有多取代基。
• Super-oxide dismutase mimetics
  申请人：Galera Labs, LLC

  公开号：US10350193B2

  公开（公告）日：2019-07-16

  The present invention relates to compounds which are effective as catalysts for dismutating superoxide and, more particularly, the manganese or iron complexes of substituted, unsaturated heterocyclic 16-membered macrocyclic complexes that catalytically dismutate superoxide. It also relates to methods of using these complexes to reduce the concentration or the effects of superoxide, pharmaceutical compositions comprising these compounds or their metal complexes, and methods of treating conditions associated with excessive superoxide activity.

  本发明涉及可有效作为催化剂分解超氧化物的化合物，特别是可催化分解超氧化物的取代的不饱和杂环16元大环络合物的锰或铁络合物。它还涉及使用这些络合物降低超氧化物浓度或影响的方法、包含这些化合物或其金属络合物的药物组合物，以及治疗与过量超氧化物活性相关的病症的方法。
• Toward the Rational Design of Superoxide Dismutase Mimics:  Mechanistic Studies for the Elucidation of Substituent Effects on the Catalytic Activity of Macrocyclic Manganese(II) Complexes
  作者：Dennis P. Riley、Patrick J. Lennon、William L. Neumann、Randy H. Weiss

  DOI：10.1021/ja964271e

  日期：1997.7.1

  Two new isomeric bis(trans-fused cyclohexano) substituted 1,4,7,10,13-pentaazacyclopentadecane ligands and their Mn(II) complexes, 3 and 14, have been synthesized, and their activity as superoxide dismutase (SOD) catalysts has been studied. Complex 3 is an excellent SOD catalyst with a second-order rate constant at pH 7.4 of 1.2 x 10(+8) M-1 s(-1). In contrast, the isomeric complex 4 has virtually no detectable catalytic SOD activity, implying the need to understand the effect that the position, number, and stereochemistry of substituents exert on the catalytic rate. The crystal structure of the complex 4 was determined and reveals that the Mn(II) ion is coordinated in a pentagonal bipyramid array of the dye nitrogens of the macrocyclic ligand and capped by two trans-chloro ligands. Crystal data for MnC18H37Cl2N5 are as follows: triclinic at 20 degrees C, space group P-1-C(i)2 (no. 2); a = 9.746(3) Angstrom, b = 12.631(6) Angstrom, c = 11.311(5) Angstrom; alpha = 73.14(4)degrees, beta = 76.39(3)degrees, gamma = 79.98(3)degrees, V = 1287(1) Angstrom(3), and Z = 2 (rho(calc) = 1.279 g/cm(3); mu(2) Mo K-alpha = 6.23 mm(-1)). Mechanistic studies with the complex 3 and the pentamethyl susbstituted complex, 5, including D2O rate studies, are reported and are consistent with the existence of two pathways for the rate-determining electron-transfer from Mn(II) to superoxide: (1) hydrogen atom transfer from a bound water on Mn(IP) to HO2. to yield a Mn(III) hydroxo intermediate and (2) the dissociative pathway in which superoxide anion binds to a vacant coordination site on Mn(II) followed by protonation/oxidation to yield a Mn(III)hydroperoxo species. Subsequent reduction of the intermediate Mn(III) with superoxide anion completes the catalytic cycle. Substituent effects on the rates and relative contribution of the two pathways to the overall rate of SOD activity is ascribed to the propensity of the ligand to fold around Mn(II) forming a pseudo-octahedral complex similar in geometry to the oxidized Mn(III) complex. Folding of the pentaaza macrocyclic ligand is confirmed as a relevant structural motif for this series of Mn(TI) complexes by the X-ray structure determination of the bis(nitrate) derivative of 1, [Mn(C10H25N5)NO3]NO3, which reveals a six-coordinate structure with a folded conformation of the macrocyclic ligand. Crystal data for [Mn(C10H25N5)NO3]NO3: orthorhombic at -100 degrees C, space group P2(1)2(1)2(1); a = 9.457(2) Angstrom, b = 12.758(2) Angstrom, c = 13.834(2) Angstrom, V = 1669.1(5) Angstrom(3), and Z = 4 (rho(calc) = 1.549 g/cm(3)).
• Pseudopeptide synthesis of a pentaazamacrocycle containing two trans-fused cyclohexane rings
  作者：William L Neumann、Gary W. Franklin、Kirby R. Sample、Karl W. Aston、Randy H. Weiss、Dennis P. Riley、Nigam Rath

  DOI：10.1016/s0040-4039(97)00563-7

  日期：1997.5

  The synthesis of a bis-cyclohexyl-fused pentaazamacrocycle via head-to-tail pseudopeptide cyclization chemistry is described. The bis-cyclohexyl-fused cyclic pseudopeptide 11 displays intramolecular hydrogen bonding which has been characterized by variable temperature NMR spectroscopy and X-Ray Crystallography. (C) 1997 Elsevier Science Ltd.
• Iron(III) Complexes as Superoxide Dismutase Mimics:  Synthesis, Characterization, Crystal Structure, and Superoxide Dismutase (SOD) Activity of Iron(III) Complexes Containing Pentaaza Macrocyclic Ligands
  作者：DeLong Zhang、Daryle H. Busch、Patrick L. Lennon、Randy H. Weiss、William L. Neumann、Dennis P. Riley

  DOI：10.1021/ic970861h

  日期：1998.3.9

  Iron(III) complexes with four pentaaza macrocylic ligands, [Fe(L)Cl-2](PF6), have been synthesized, where the ligand L is 1,4,7,10,13-pentaazacyclopentadecane (L-1), 2R,3R,8S,9S-dicyclohexano-1,4,7,10,13-pentaazacyclopentadecane L-2), 2R,3R,8R,9R-dicyclohexano-1,4,7,10,13-pentaazacyclopentadecane (L-3), or 2S,5R,8S,11R,14S-pentamethyl-1,4,7,10,13-pentaazacyclopentadecane (L-4), respectively. Conductivity measurements in acetonitrile are consistent with two chloro anions coordinated to iron(III). In acetonitrile solution, all four iron complexes exhibit a reversible or quasi-reversible redox couple in the experimental range -1.5 to +1.5 V vs EAg/Ag+, and the redox potentials for those four complexes are similar (from -0.15 to -0.19 V vs NHE). In aqueous solutions, the electrochemical properties of those complexes are different from these in acetonitrile solution; the redox peaks shift more than 0.5 V more positive. The complexes with L-1, L-2, and L-3 display a reversible redox at 0.35, 0.45, and 0.43 V vs NHE, respectively, while [Fe(L-4)Cl-2](PF6) shows a cathodic peak at 0.44 V and two anodic peaks at 0.31 and 0.14 V vs NHE, respectively. The base titration results reveal that two water molecules are coordinated to the iron(III) in these complexes, pK(a1) and pK(a2): 3.46(7) and 7.31(7) for [Fe(L-1)Cl-2](PF6); 3.7(1) and 7.50(2) for [Fe(L-2)Cl-2](PF6); 4.1(1) and 7.73(2) for [Fe(L-3)Cl-2](PF6); 3.6(7) and 7.4(2) for [Fe(L-4)Cl-2](PF6). The superoxide dismutase (SOD) activity, assessed by stopped-flow experiments, reveals that all four metal complexes catalyze the fast disproportionation of superoxide in aqueous solution: at pH = 7.8, the catalyic rate constants for the complexes were 0.81 x 10(7), 1.42 x 10(7), 1.41 x 10(7), and 0.29 x 10(7) M-1 s(-1) for [Fe(L-1)Cl-2](PF6), [Fe(L-2)Cl-2](PF6), [Fe(L-3)Cl-2](PF6), and [Fe(L-4)Cl-2](PF6), respectively. The crystal structure of [Fe(L-2)Cl-2](PF6) was determined. Crystal data: triclinic, ; a = 7.367(2), b = 10.707(2), c = 17.632(2) Angstrom; alpha = 81.27(2), beta = 79.74(2), gamma = 83.38(2)degrees; R = 0.0465 for observed data (I > 2 sigma(I)). The iron is seven-coordinate with five nitrogen atoms from the pentaaza macrocylic ligand and trans-chloro anions in a pentagonal bipyramidal arrangement. The average bond lengths for Fe-N and Fe-Cl are 2.271 and 2.339 Angstrom, respectively.