tris[N-(tert-butoxycarbonyl)-β-alanyl]-1,6,20,25-tetraaza[6.16.1]paracyclophane | 866414-09-7

• 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: tris[N-(tert-butoxycarbonyl)-β-alanyl]-1,6,20,25-tetraaza[6.16.1]paracyclophane
• 英文别名: tris(t-butyloxycarbonyl-β-alanyl)tetraaza[6.1.6.1]paracyclophane；N,N',N''-tris[2-(tert-butoxycarbonylamino)propionyl]-1,6,20,25-tetraaza[6.1.6.1]paracyclophane；tris(Boc-β-alanyl)tetraaza[6.1.6.1]paracyclophane；tert-butyl N-[3-[12,22-bis[3-[(2-methylpropan-2-yl)oxycarbonylamino]propanoyl]-7,12,22,27-tetrazapentacyclo[26.2.2.23,6.213,16.218,21]octatriaconta-1(30),3(38),4,6(37),13(36),14,16(35),18,20,28,31,33-dodecaen-7-yl]-3-oxopropyl]carbamate
• CAS: 866414-09-7
• 化学式: C₅₈H₇₉N₇O₉
• 分子量: 1018.31
• InChiKey: FVQQFNZREOIMMB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.6
• 重原子数：
  74
• 可旋转键数：
  15
• 环数：
  11.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  188
• 氢给体数：
  4
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  tris[N-(tert-butoxycarbonyl)-β-alanyl]-1,6,20,25-tetraaza[6.16.1]paracyclophane 、 FMOC-beta-丙氨酸 在 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 3.33h， 以96%的产率得到tert-butyl N-[3-[12-[3-(9H-fluoren-9-ylmethoxycarbonylamino)propanoyl]-22,27-bis[3-[(2-methylpropan-2-yl)oxycarbonylamino]propanoyl]-7,12,22,27-tetrazapentacyclo[26.2.2.23,6.213,16.218,21]octatriaconta-1(30),3(38),4,6(37),13(36),14,16(35),18,20,28,31,33-dodecaen-7-yl]-3-oxopropyl]carbamate
  参考文献：
  名称：

  Guest Binding, Cellular Uptake, and Molecular Delivery of Water-soluble Cyclophanes Having a Pyrene Moiety

  摘要：

  合成了含有芘 1 的阳离子水溶性环烷，作为阴离子客体分子的宿主。研究发现，阳离子宿主 1 能有效地与人类肝母细胞 HepG2 细胞结合。此外，8-苯胺萘-1-磺酸盐（ANS）本身具有较差的细胞渗透性，在 1 的存在下，通过形成宿主-客体复合物被吸收到细胞中。

  DOI：

  10.1246/cl.2010.1321
• 作为产物：
  描述：

  Boc-beta-丙氨酸 、 1.6.20.25-四偶氮[6.1.6.1]环苯 在 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 以25%的产率得到tris[N-(tert-butoxycarbonyl)-β-alanyl]-1,6,20,25-tetraaza[6.16.1]paracyclophane
  参考文献：
  名称：

  Preparation and Multivalently Enhanced Guest-Binding Affinity of Water-Soluble Cyclophane Heptadecamers

  摘要：

  Water-soluble cyclophane heptadecamers (17a and 17b), which were constructed with the core cyclophane heptadecamer and 36 polar side chains with a terminal galactose or glucose residue, respectively, were prepared. An analogous cyclophane pentamer (5a) was also prepared. The stoichiometry for the complex of the cyclophane oligomers with fluorescence guests such as TNS was confirmed to be 1:1 host:guest by a Job plot. The guest-binding affinity of cyclophane heptadecamers 17a and 17b was much enhanced relative to that of a corresponding monocyclic cyclophane (1a), i.e., the 1:1 binding constant (K) values for 17a with TNS, 2,6-ANS, and 1,8-ANS were ca. 1700-, 1600-, and 1500-fold larger than those of 1a for the identical guests, respectively, which reflects the multivalency effects in macrocycles. Meanwhile, the corresponding K values for the cyclophane pentamer 5a with TNS, 2,6-ANS, and 1,8-ANS were ca. 250-, 250-, and 110-fold larger than those of 1a for the identical guest, respectively.

  DOI：

  10.1021/jo800129j

文献信息

• Synthesis of Water-soluble Tris(cyclophane) Hosts and Surface Plasmon Resonance Study on Guest-binding Interaction with Immobilized Guests
  作者：Osamu Hayashida、Atsushi Kitaura

  DOI：10.1246/cl.2006.808

  日期：2006.7

  Tris(cyclophane) derivatives were prepared as water-soluble hosts by connecting three macrocyclic skeletons. The present hosts showed enhanced guest-binding affinity relative to that by simple cyclophane, as confirmed by surface plasmon resonance measurements.

  通过连接三个大环骨架，制备了三(环烷)衍生物作为水溶性宿主。经表面等离子体共振测量证实，与简单的环烷相比，本宿主具有更强的客体结合亲和力。
• Synthesis and Characterization of Reduction-responsive Cyclophane Dimer Based on Disulfide Linkage
  作者：Osamu Hayashida、Kazuaki Ichimura

  DOI：10.1246/cl.2012.1650

  日期：2012.12.5

  Reduction-responsive cyclophane dimer having a disulfide linkage was synthesized. The host showed enhanced guest binding affinity relative to that by monocyclic cyclophane, as confirmed by fluorescence spectroscopy. Reduction of the disulfide bond of the host by dithiothreitol gave monocyclic cyclophanes having less guest-binding affinity.

  合成了具有二硫键的还原响应性环芳二聚体。与单环环芳相比，该主客体结合亲和力更强，这一点已通过荧光光谱法得到证实。用二硫苏糖醇还原主客体的二硫键，可得到结合亲和力较低的单环环芳。
• Synthesis and guest-binding study of polytopic multi(cyclophane) hosts
  作者：Osamu Hayashida、Yousuke Takaoka、Itaru Hamachi

  DOI：10.1016/j.tetlet.2005.07.010

  日期：2005.9

  Novel bis(cyclophanes) bearing glucosides and pentakis(cyclophanes) bearing glucosides were prepared as water-soluble hosts by connecting two or five macrocyclic skeletons, respectively. The guest-binding affinities of the present bis(cyclophanes) and pentakis(cyclophanes) toward a hydrophobic dye, 6-p-toluidinonaphthalene-2-sulfonate, were enhanced 13- and 1200-fold, respectively, relative to that

  通过分别连接两个或五个大环骨架，将新型的含葡萄糖苷的双（环烷）和含葡萄糖的五环（环烷）制备为水溶性主体。相对于相应的单环，本发明的双（环烷）和五（环）对疏水染料6-对甲苯二萘基萘-2-磺酸的客体结合亲和力分别提高了13-和1200-倍。环烷，反映了大环化合物的多价效应。
• Surface Recognition and Fluorescence Sensing of Histone by Dansyl-Appended Cyclophane-Based Resorcinarene Trimer
  作者：Osamu Hayashida、Naoyuki Ogawa、Masaki Uchiyama

  DOI：10.1021/ja074906h

  日期：2007.11.1

  A cyclophane-based resorcinarene trimer (3) bearing a dansyl moiety as an environmentally sensitive fluorophore was prepared by stepwise condensation of a tetraaza[6.1.6.1]paracyclophane skeleton with a dansyl moiety and three resorcinarene derivatives having heptacarboxylic acid residues in this sequence. The dansyl-appended cyclophane exhibited the following fluorescence properties regarding solvent polarity dependency and histone surface recognition: With increasing dioxane contents in dioxane/water solvents, the fluorescence intensity originating from the dansyl moiety of 3 increased along with a concomitant blue shift of the fluorescence maximum (lambda(em)). The microenvironmentally sensitive fluorescence properties of dansyl fluorophore were maintained, even when the dansyl moiety was covalently attached to a cyclophane. Most interestingly, the cyclophane-based resorcinarene trimer exhibited recognition and fluorescence sensing capabilities toward histone, a small basic protein of eukaryotic chromatins. The fluorescence intensity originating from 3 increased along with a concomitant blue shift Of e upon the addition of histone, reflecting the formation of 3-histone complexes. A relatively large fluorescence polarization (P) value was obtained for the 3-histone complexes (0.15), reflecting highly restricted conformations of 3, and the obtained P value was much larger than that of 3 alone in aqueous medium (0.07). The binding constant (K) of 3 with histone (unit basis) was estimated to be 2.1 x 10(6) M-1. On the other hand, upon the addition of acetylated histone (Ac-histone) to an aqueous solution containing 3, the extent of change in fluorescence intensity originating from the dansyl group of 3 was almost negligible, indicating that the electrostatic interactions between 3 and Ac-histone were weak. In addition, the fluorescence spectral changes were also small or negligible upon the addition of other proteins such as albumin. ovalbumin, peanut agglutinin, myoglobin, concanavalin A, cytochrome c, and lysozyme, having isoelectric points of 4.7, 4.8, 5.7-6.7, 6.8, 7.1, 9, and 11.0, respectively, to an aqueous solution containing 3.
• Synthesis of Dabsyl-Appended Cyclophanes and Their Heterodimer Formation with Pyrene-Appended Cyclophanes
  作者：Osamu Hayashida、Yu Kaku

  DOI：10.1021/jo4018843

  日期：2013.10.18

  As a quencher-type host, dabsyl-appended cyclophanes bearing positively and negatively charged side chains (1a and 1b, respectively) were synthesized. Formation of cyclophane heterodimers of 1a with anionic fluorescent cyclophane bearing a pyrene moiety 2b was confirmed by fluorescence titration experiments. The 1:1 binding constant (K) of 1a toward 2b was calculated to be 1.6 x 10(5) M-1. On the other hand, almost no complexation affinity of 1a toward cationic analogue of fluorescent cyclophane 2a was confirmed by the identical methods, indicating that electrostatic interactions became effective in the formation of cyclophane heterodimers. In addition, van't Hoff analysis applied to the temperature-dependent K values for the heterodimer formation gave negative enthalpy (Delta H) and entropy changes (Delta S). The large and negative Delta H values as well as small and also negative Delta S values showed that the complexation is an exothermic and enthalpy-controlled but not entropy-driven process. A similar trend of molecular recognition was also confirmed for formation of cyclophane heterodimers of 1b with 2a by the identical methods.