cis-1,8-bis(pyridin-3-oxy)oct-4-ene-2,6-diyne | 442520-82-3

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: cis-1,8-bis(pyridin-3-oxy)oct-4-ene-2,6-diyne
• 英文别名: 1,8-bis(pyridine-3-oxy)oct-4-ene-2,6-diyne；1,8-bis(pyridin-3-oxy)oct-4-ene-2,6-diyne；bpod；3-[(Z)-8-pyridin-3-yloxyoct-4-en-2,6-diynoxy]pyridine
• CAS: 442520-82-3
• 化学式: C₁₈H₁₄N₂O₂
• 分子量: 290.321
• InChiKey: VOGLRDUJEDDIJK-UPHRSURJSA-N

物化性质

• 沸点：
  484.2±45.0 °C(Predicted)
• 密度：
  1.189±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  44.2
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  cis-1,8-bis(pyridin-3-oxy)oct-4-ene-2,6-diyne 在 copper(II) nitrate 、 1,4-环己二烯 作用下， 以 甲醇 为溶剂， 反应 12.0h， 生成 3-[[2-(Pyridin-3-yloxymethyl)phenyl]methoxy]pyridine
  参考文献：
  名称：

  Metalloenediynes:  Ligand Field Control of Thermal Bergman Cyclization Reactions

  摘要：

  We report the preparation and thermal reactivities of unique Cu(I) and Cu(II) metalloenediyne complexes of the flexible 1,8-bis(pyridine-3-oxy)oct-4-ene-2,6-diyne ligand (bpod, 1). The thermal reactivities of these metalloenediynes are intimately modulated by metal oxidation state. Using differential scanning calorimetry (DSC), we demonstrate that the [Cu(bpod)(2)](+) complex (2) undergoes Bergman cyclization at 203 degrees C, whereas the Cu(II) analogue (3) is substantially more reactive and cyclizes at 121 OC. Similar results are also observed for mixed ligand [Cu(bpod)(pyridine)2](+/2+) analogues 4 (194 degrees C) and 5 (116 degrees C), suggesting that both complexes of a given oxidation state have comparable structures. The Cu(bpod)Cl-2 compound (6) exhibits a cyclization temperature (152 degrees C) midway between the those of Cu(I) and Cu(II) complexes, which can be explained by the propensity for cis-CuN2Cl2 structures to exhibit dihedral angle distortion. The oxidation-state-dependent thermal reactivity is unprecedented and reflects the influence of the ligand field geometry on the barrier to enediyne cyclization. On the basis of X-ray structures of Cu(pyridine)lt complexes, 2 and 4 are proposed to be tetrahedral. In contrast, the electronic absorption spectra of 3 and 5 each show a broad envelope that can be Gaussian resolved into three ligand field transitions characteristic of a Cu(II) center in a tetragonal octahedral environment. This structural assignment is confirmed by the EPR spin Hamiltonian parameters (g(parallel to)/A(parallel to) (cm) = 134 (3), 138 (5)) and is consistent with crystallographically characterized Cu(pyridine)(4)X-2 structures. Molecular mechanics calculations have independently derived comparable tetrahedral and tetragonal structures for 2 and 3, respectively, and determined the average alkyne termini separation to be [a] = 4.0 Angstrom for 2 and 3.6 Angstrom for 3. Thus, the tetrahedral geometries of the copper centers in 2 and 4 increase the distance between alkyne termini relative to the tetragonal Cu(II) geometries of 3 and 5, and are therefore responsible for the increase in the thermal cyclization temperatures. The DSC and spectroscopic data for 6 support these conclusions, as the latter suggests a distorted four-coordinate structure in the solid state, and a six-coordinate geometry in solution, which gives rise to an intermediate Bergman cyclization temperature. Overall, our results emphasize the utility of newly emerging metalloenediyne complexes for controlling thermal Bergman cyclization reactions and provide insights into designing novel, pharmacologically useful metalloenediyne compounds.

  DOI：

  10.1021/ja0017918
• 作为产物：
  描述：

  (4Z)-1,8-bis-(tetrahydropyran-2-yloxy)-oct-4-ene-2,6-diyne 在 氢氧化钾 、 溴 、 三苯基膦 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.25h， 生成 cis-1,8-bis(pyridin-3-oxy)oct-4-ene-2,6-diyne
  参考文献：
  名称：

  Metalloenediynes:  Ligand Field Control of Thermal Bergman Cyclization Reactions

  摘要：

  We report the preparation and thermal reactivities of unique Cu(I) and Cu(II) metalloenediyne complexes of the flexible 1,8-bis(pyridine-3-oxy)oct-4-ene-2,6-diyne ligand (bpod, 1). The thermal reactivities of these metalloenediynes are intimately modulated by metal oxidation state. Using differential scanning calorimetry (DSC), we demonstrate that the [Cu(bpod)(2)](+) complex (2) undergoes Bergman cyclization at 203 degrees C, whereas the Cu(II) analogue (3) is substantially more reactive and cyclizes at 121 OC. Similar results are also observed for mixed ligand [Cu(bpod)(pyridine)2](+/2+) analogues 4 (194 degrees C) and 5 (116 degrees C), suggesting that both complexes of a given oxidation state have comparable structures. The Cu(bpod)Cl-2 compound (6) exhibits a cyclization temperature (152 degrees C) midway between the those of Cu(I) and Cu(II) complexes, which can be explained by the propensity for cis-CuN2Cl2 structures to exhibit dihedral angle distortion. The oxidation-state-dependent thermal reactivity is unprecedented and reflects the influence of the ligand field geometry on the barrier to enediyne cyclization. On the basis of X-ray structures of Cu(pyridine)lt complexes, 2 and 4 are proposed to be tetrahedral. In contrast, the electronic absorption spectra of 3 and 5 each show a broad envelope that can be Gaussian resolved into three ligand field transitions characteristic of a Cu(II) center in a tetragonal octahedral environment. This structural assignment is confirmed by the EPR spin Hamiltonian parameters (g(parallel to)/A(parallel to) (cm) = 134 (3), 138 (5)) and is consistent with crystallographically characterized Cu(pyridine)(4)X-2 structures. Molecular mechanics calculations have independently derived comparable tetrahedral and tetragonal structures for 2 and 3, respectively, and determined the average alkyne termini separation to be [a] = 4.0 Angstrom for 2 and 3.6 Angstrom for 3. Thus, the tetrahedral geometries of the copper centers in 2 and 4 increase the distance between alkyne termini relative to the tetragonal Cu(II) geometries of 3 and 5, and are therefore responsible for the increase in the thermal cyclization temperatures. The DSC and spectroscopic data for 6 support these conclusions, as the latter suggests a distorted four-coordinate structure in the solid state, and a six-coordinate geometry in solution, which gives rise to an intermediate Bergman cyclization temperature. Overall, our results emphasize the utility of newly emerging metalloenediyne complexes for controlling thermal Bergman cyclization reactions and provide insights into designing novel, pharmacologically useful metalloenediyne compounds.

  DOI：

  10.1021/ja0017918

文献信息

• Compounds, composition, and methods for photodynamic therapy
  申请人：Advanced Research and Technology Institute, Inc.

  公开号：US06828439B1

  公开（公告）日：2004-12-07

  Disclosed are novel compounds, compositions, and methods that are particularly useful in photodynamic therapy. In particular, the inventive compounds, compositions, and methods relate to the formation of cytotoxic radical species in the presence of light. Significantly, the compounds, compositions, and methods of the present invention do not require the presence of oxygen in the photodynamic therapy and, as such, rely on a unimolecular mechanism for producing the radicals. The inventive compounds, compositions, and methods can be used, for example, in the treatment of cancers as well as infections caused by microorganisms such as protozoa, fungi, bacteria, and viruses.

  揭示了一种在光动力疗法中特别有用的新化合物、组合物和方法。具体来说，这些创新化合物、组合物和方法涉及在光的存在下形成细胞毒性自由基物质。值得注意的是，本发明的化合物、组合物和方法在光动力疗法中不需要氧气的存在，因此依赖于产生自由基的单分子机制。这些创新的化合物、组合物和方法可以用于治疗癌症以及由原生动物、真菌、细菌和病毒引起的感染。
• Metal−Ligand Charge-Transfer-Promoted Photoelectronic Bergman Cyclization of Copper Metalloenediynes:  Photochemical DNA Cleavage via C-4‘ H-Atom Abstraction
  作者：Pedro J. Benites、Rebecca C. Holmberg、Diwan S. Rawat、Brian J. Kraft、Lee J. Klein、Dennis G. Peters、H. Holden Thorp、Jeffrey M. Zaleski

  DOI：10.1021/ja020939f

  日期：2003.5.1

  to the Zn(II) cation by photoisomerization. Electrochemical studies show that 1, both the uncomplexed and complexed, exhibits two irreversible waves between E(p) values of -1.75 and -1.93 V (vs SCE), corresponding to reductions of the alkyne units. Irreversible, ligand-based one-electron oxidation waves are also observed at +1.94 and +2.15 V (vs SCE) for 1 and 3. Copper-centered oxidation of 2 and reduction

  金属-配体电荷转移 (MLCT) 光解 (λ > 或 = 395 nm) cis-1,8-bis(pyridin-3-oxy)oct-4-ene-2,6-diyne ( bpod, 1), [Cu(bpod)(2)]PF(6) (2), and [Cu(bpod)(2)](NO(3))(2) (3) 产生结合的伯格曼环化配体。相比之下，未复合的配体 1 和 Zn(bpod)(2)(CH(3)COO)(2) 化合物 (4) 在相同条件下是光化学惰性的。在 4 的情况下，位于烯二炔单元上的最低能量 (3)pi-pi 状态的敏化光化学生成导致通过光异构化与 Zn(II) 阳离子结合的反式 bpod 配体的产生。电化学研究表明，1，无论是未络合的还是络合的，都在 E(p) 值介于 -1.75 和 -1.93 V（vs SCE）之间表现出两个不可逆波，对应于炔烃单位的减少。不可逆转，对于 1 和 3，在
• A CONVENIENT METHOD FOR THE SYNTHESIS OF 1,8-<i>BIS</i>(PYRIDIN- 3-OXY)OCT-4-ENE-2,6-DIYNE
  作者：Diwan S. Rawat、Jeffrey M. Zaleski

  DOI：10.1081/scc-120004137

  日期：2002.1

  A convenient and rapid synthesis of the title compound is described. The key step in the procedure is the Stephens Castro coupling of 3-prop-2-ynyloxy-pyridine with cis-1,2-dichloroethylene and subsequent column purification in the final stage.
• Metalloenediynes:  Ligand Field Control of Thermal Bergman Cyclization Reactions
  作者：Pedro J. Benites、Diwan S. Rawat、Jeffrey M. Zaleski

  DOI：10.1021/ja0017918

  日期：2000.8.1

  We report the preparation and thermal reactivities of unique Cu(I) and Cu(II) metalloenediyne complexes of the flexible 1,8-bis(pyridine-3-oxy)oct-4-ene-2,6-diyne ligand (bpod, 1). The thermal reactivities of these metalloenediynes are intimately modulated by metal oxidation state. Using differential scanning calorimetry (DSC), we demonstrate that the [Cu(bpod)(2)](+) complex (2) undergoes Bergman cyclization at 203 degrees C, whereas the Cu(II) analogue (3) is substantially more reactive and cyclizes at 121 OC. Similar results are also observed for mixed ligand [Cu(bpod)(pyridine)2](+/2+) analogues 4 (194 degrees C) and 5 (116 degrees C), suggesting that both complexes of a given oxidation state have comparable structures. The Cu(bpod)Cl-2 compound (6) exhibits a cyclization temperature (152 degrees C) midway between the those of Cu(I) and Cu(II) complexes, which can be explained by the propensity for cis-CuN2Cl2 structures to exhibit dihedral angle distortion. The oxidation-state-dependent thermal reactivity is unprecedented and reflects the influence of the ligand field geometry on the barrier to enediyne cyclization. On the basis of X-ray structures of Cu(pyridine)lt complexes, 2 and 4 are proposed to be tetrahedral. In contrast, the electronic absorption spectra of 3 and 5 each show a broad envelope that can be Gaussian resolved into three ligand field transitions characteristic of a Cu(II) center in a tetragonal octahedral environment. This structural assignment is confirmed by the EPR spin Hamiltonian parameters (g(parallel to)/A(parallel to) (cm) = 134 (3), 138 (5)) and is consistent with crystallographically characterized Cu(pyridine)(4)X-2 structures. Molecular mechanics calculations have independently derived comparable tetrahedral and tetragonal structures for 2 and 3, respectively, and determined the average alkyne termini separation to be [a] = 4.0 Angstrom for 2 and 3.6 Angstrom for 3. Thus, the tetrahedral geometries of the copper centers in 2 and 4 increase the distance between alkyne termini relative to the tetragonal Cu(II) geometries of 3 and 5, and are therefore responsible for the increase in the thermal cyclization temperatures. The DSC and spectroscopic data for 6 support these conclusions, as the latter suggests a distorted four-coordinate structure in the solid state, and a six-coordinate geometry in solution, which gives rise to an intermediate Bergman cyclization temperature. Overall, our results emphasize the utility of newly emerging metalloenediyne complexes for controlling thermal Bergman cyclization reactions and provide insights into designing novel, pharmacologically useful metalloenediyne compounds.