2,5-dioxopyrrolidin-1-yl 4-oxo-4-(9,13,18-tris(3-((tert-butoxycarbonyl)amino)propanoyl)-4,9,13,18-tetraaza-1,3,10,12(1,4)-tetrabenzenacyclooctadecaphane-4-yl)butanoate | 1293916-17-2

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 2,5-dioxopyrrolidin-1-yl 4-oxo-4-(9,13,18-tris(3-((tert-butoxycarbonyl)amino)propanoyl)-4,9,13,18-tetraaza-1,3,10,12(1,4)-tetrabenzenacyclooctadecaphane-4-yl)butanoate
• CAS: 1293916-17-2
• 化学式: C₆₆H₈₆N₈O₁₄
• 分子量: 1215.45
• InChiKey: MSQIBYJZKOSVMU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.61
• 重原子数：
  88.0
• 可旋转键数：
  13.0
• 环数：
  12.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  259.91
• 氢给体数：
  3.0
• 氢受体数：
  14.0

反应信息

• 作为反应物：
  描述：

  L-赖氨酸 、 2,5-dioxopyrrolidin-1-yl 4-oxo-4-(9,13,18-tris(3-((tert-butoxycarbonyl)amino)propanoyl)-4,9,13,18-tetraaza-1,3,10,12(1,4)-tetrabenzenacyclooctadecaphane-4-yl)butanoate 在 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 以87%的产率得到N2,N6-bis(4-oxo-4-(9,13,18-tris(3-((tert-butoxycarbonyl)amino)propanoyl)-4,9,13,18-tetraaza-1,3,10,12(1,4)-tetrabenzenacyclooctadecaphane-4-yl)butanoyl)-L-lysine
  参考文献：
  名称：

  Synthesis of Peptide-Based Cyclophane Oligomers Having Multivalently Enhanced Guest-Binding Affinity

  摘要：

  通过用赖氨酸和相应的赖氨酸肽作为支架，对四氮杂[6.1.6.1]对环芳烷的琥珀酰亚胺酯衍生物进行胺解反应，随后去除保护基团，制备了水溶性环芳烷二聚体、三聚体、四聚体和五聚体。与单环环芳烷相比，这些环芳烷寡聚体对6-对甲苯氨基萘-2-磺酸盐等荧光客体显示出增强的客体结合亲和力，反映了大环中的多价效应。通过表面等离子体共振（SPR）测量，也证实了多价大环对这些环芳烷寡聚体的客体结合的影响。

  DOI：

  10.1246/bcsj.20120076
• 作为产物：
  描述：

  N,N',N''-tris[2-(tert-butoxycarbonylamino)propionyl]-N'''-(3-carboxypropionyl)-1,6,20,25-tetraaza[6.1.6.1]paracyclophane 在 N-羟基丁二酰亚胺 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 以71%的产率得到2,5-dioxopyrrolidin-1-yl 4-oxo-4-(9,13,18-tris(3-((tert-butoxycarbonyl)amino)propanoyl)-4,9,13,18-tetraaza-1,3,10,12(1,4)-tetrabenzenacyclooctadecaphane-4-yl)butanoate
  参考文献：
  名称：

  Synthesis of Peptide-Based Cyclophane Oligomers Having Multivalently Enhanced Guest-Binding Affinity

  摘要：

  通过用赖氨酸和相应的赖氨酸肽作为支架，对四氮杂[6.1.6.1]对环芳烷的琥珀酰亚胺酯衍生物进行胺解反应，随后去除保护基团，制备了水溶性环芳烷二聚体、三聚体、四聚体和五聚体。与单环环芳烷相比，这些环芳烷寡聚体对6-对甲苯氨基萘-2-磺酸盐等荧光客体显示出增强的客体结合亲和力，反映了大环中的多价效应。通过表面等离子体共振（SPR）测量，也证实了多价大环对这些环芳烷寡聚体的客体结合的影响。

  DOI：

  10.1246/bcsj.20120076

文献信息

• Synthesis of Cyclophane Dimer Using Cyclophane-tethered Fmoc-amino Acid Derivatives as a Multivalent Host
  作者：Osamu Hayashida、Tomomi Nakashima

  DOI：10.1246/cl.2011.134

  日期：2011.2.5

  Water-soluble cyclophane dimer was synthesized by Fmoc-chemistry of cyclophane-tethered Fmoc-lysine derivative, as a multivalent host. The host showed enhanced guest binding affinity relative to that by monocyclic cyclophane, as confirmed by fluorescence spectroscopy as well as surface plasmon resonance measurements.

  通过Fmoc化学合成了水溶性环烯烃二聚体，作为一种多价宿主。这种宿主相对于单环环烯烃显示出更强的客体结合亲和力，使用荧光光谱和表面等离子共振测量进行了确认。
• Synthesis and effect of linker length on guest-binding affinity of water-soluble tetraazacyclophane dimers
  作者：Osamu Hayashida、Koji Matsushita、Shuhei Kusano

  DOI：10.1007/s10847-016-0602-7

  日期：2016.4

  Cationic cyclophane dimers which are constructed with two tetraaza[6.1.6.1]para-cyclophanes and a short or long hydrophilic linker interposed between them were synthesized as a water-soluble host (1a and 1b, respectively). The binding constant (K) values of 1a having a short linkage with fluorescence guests such as 6-p-toluidinonaphthalene-2-sulfonate and 6-anilinonaphthalene-2-sulfonate were about 2-fold larger than those of 1b having a long one with the identical guests. Local concentration in the macrocycles of 1a was more effective than that of 1b for such enhancements of the guest-binding affinity. Moreover, the K values of cationic cyclophane dimer having a short hydrophobic linkage 1c were comparable to those by 1a, indicating that guest-binding affinity was less affected on the hydrophilic/hydrophobic characteristics of these short linkers.

  合成了由两个四氮杂[6.1.6.1]对环烷和插入它们之间的短或长亲水连接体构建的阳离子环烷二聚体作为水溶性主体（分别为1a和1b）。与荧光客体如6-对甲苯胺萘-2-磺酸酯和6-苯胺萘-2-磺酸酯具有短键的1a的结合常数(K)值比具有长键的1b大约2倍相同的客人。对于这种客体结合亲和力的增强，1a 大环中的局部浓度比 1b 更有效。此外，具有短疏水键1c的阳离子环烷二聚体的K值与1a相当，表明客体结合亲和力对这些短连接体的亲水/疏水特性影响较小。
• Synthesis and Guest-Binding Properties of pH/Reduction Dual-Responsive Cyclophane Dimer
  作者：Osamu Hayashida、Yudai Tanaka、Takaaki Miyazaki

  DOI：10.3390/molecules26113097

  日期：——

  A water-soluble cyclophane dimer having two disulfide groups as a reduction-responsive cleavable bond as well as several acidic and basic functional groups as a pH-responsive ionizable group 1 was successfully synthesized. It was found that 1 showed pH-dependent guest-binding behavior. That is, 1 strongly bound an anionic guest, 6-p-toluidinonaphthalene-2-sulfonate (TNS) with binding constant (K/M−1)

  成功地合成了具有两个二硫键作为还原反应性可裂解键以及几个酸性和碱性官能团作为pH响应可离子化基团1的水溶性环烷二聚体。发现1显示出pH依赖性的客体结合行为。也就是说，在pH为9.6×10 4 M -1的1：1主客体络合物中，有1个阴离子客体6-对甲苯基萘并-2-磺酸（TNS）具有恒定的结合常数（K / M -1）3.8，大于pH 7.4和10.7（6.0×10 4和2.4×10 4 M -1，分别），表明阴离子客体和净阳离子1之间有利的静电相互作用。而且，pH刺激很容易控制被捕获的客体分子释放1。在所用的pH条件下，获得了形成宿主-客体复合物的较大的有利焓（ΔH），这表明阴离子TNS和1之间的静电相互作用是宿主-客体复合的最重要驱动力。从酸性溶液到碱性溶液，随着pH值的增加，这种ΔH对宿主-客体复合物形成的贡献降低。将二硫苏糖醇（DTT）作为还原剂添加到含有1的PBS水溶液（pH 7.4）
• Self-Aggregation, Enhanced Guest-Binding Behavior, and Anion-Induced Agglutination of Cyclophane Dimers Linked with Florescent Perylene Diimide
  作者：Osamu Hayashida、Yuya Araki、Takaaki Miyazaki

  DOI：10.1021/acs.joc.4c00183

  日期：2024.6.7

  Cationic, anionic, and nonionic cyclophane dimers, 1a, 1b, and 1c, covalently linked with fluorescent perylene diimide were synthesized, respectively, as a host for aggregation-induced multivalent effects on guest-binding. These PDI-linked cyclophane dimers 1a and 1b, especially 1c, formed self-aggregates in H2O-rich solvents through π-stacking interactions. Critical aggregation concentrations of 1a

  分别合成了与荧光苝二酰亚胺共价连接的阳离子、阴离子和非离子环芳二聚体1a 、 1b和1c ，作为客体结合的聚集诱导多价效应的主体。这些PDI连接的环烷二聚体1a和1b ，特别是1c ，通过π堆积相互作用在富含H 2 O的溶剂中形成自聚集体。 1a 、 1b和1c在H 2 O中的临界聚集浓度分别为4.0×10 –6 、4.0×10 –6和小于0.1×10 –6 M。通过 DLS 和 TEM 测量，PDI 连接的环芳二聚体在 H 2 O 中的自聚集体尺寸为数百纳米。在聚集状态下， 1a表现出对疏水性客体的客体结合能力，例如6-对甲苯胺萘-2-磺酸盐和6-苯胺基-萘-2-磺酸盐。此外，在添加磷酸根离子后观察到阴离子诱导的1a凝集，其有效性如下：ATP > ADP > H 2 P 2 O 7 2– > AMP ≈ PO 4 3– > HPO 4 2– > H 2 PO 4 – . 1 H NMR
• Biotinylated Cyclophane: Synthesis, Cyclophane-Avidin Conjugates, and Their Enhanced Guest-Binding Affinity
  作者：Osamu Hayashida、Miwa Kojima、Shuhei Kusano

  DOI：10.1021/acs.joc.5b01809

  日期：2015.10.2

  Cationic and anionic cyclophanes bearing a biotin moiety were synthesized as a water-soluble host (la and 1b, respectively). Both hosts la and 1b were found to strongly bind avidin with binding constants of 1.3 x 10(8)M(-1), as confirmed by surface plasmon resonance measurements. The present conjugate of la with avidin (la-avidin) showed an enhanced guest binding affinity toward fluorescence guests such as TNS and 2,6-ANS. The K values of la-avidin conjugate with TNS and 2,6-ANS were similar to 9-fold larger than those of monocyclic cyclophane la with the identical guests. Favorable hydrophobic and electrostatic interactions between la-avidin and TNS were suggested by computer-aided molecular modeling calculations. Moreover, addition of excess biotin to the complexes of la-avidin with the guests resulted in dissociation of la-avidin to avidin and la having less guest-binding affinity. Conversely, such enhancements in the guest-binding affinity were not obviously observed for the conjugate of anionic 1b with avidin (1b-avidin) due to electrostatic repulsion between anionic 1b and anionic guests.