氨基-Α-环糊精 | 30899-95-7

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 氨基-Α-环糊精
• 英文名称: hexakis(6-amino-6-deoxy)-α-cyclodextrin
• 英文别名: (1S,3R,5R,6S,8R,10R,11S,13R,15R,16S,18R,20R,21S,23R,25R,26S,28R,30R,31R,32R,33R,34R,35R,36R,37R,38R,39R,40R,41R,42R)-5,10,15,20,25,30-hexakis(aminomethyl)-2,4,7,9,12,14,17,19,22,24,27,29-dodecaoxaheptacyclo[26.2.2.23,6.28,11.213,16.218,21.223,26]dotetracontane-31,32,33,34,35,36,37,38,39,40,41,42-dodecol
• CAS: 30899-95-7
• 化学式: C₃₆H₆₆N₆O₂₄
• 分子量: 966.946
• InChiKey: JHEDOMAXMVEXLA-RWMJIURBSA-N

物化性质

• 沸点：
  1329.9±60.0 °C(Predicted)
• 密度：
  1.520±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -14.4
• 重原子数：
  66
• 可旋转键数：
  6
• 环数：
  22.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  510
• 氢给体数：
  18
• 氢受体数：
  30

反应信息

• 作为反应物：
  描述：

  氨基-Α-环糊精 、 叔丁氧羰酰基6-氨基己酸 在 4-(4,6-二甲氧基三嗪-2-基)-4-甲基吗啉盐酸盐 作用下， 以 甲醇 、 水 为溶剂， 反应 42.0h， 生成
  参考文献：
  名称：

  Design and Evaluation of Folate-Appended α-, β-, and γ-Cyclodextrins Having a Caproic Acid as a Tumor Selective Antitumor Drug Carrier in Vitro and in Vivo

  摘要：

  We reported that per-6-folic acid (FA)-appended beta-cyclodextrin (beta-CyD) possessing two caproic acids between FA and a beta-CyD molecule as a spacer (Fol-c(2)-beta-CyD) could be useful as a promising antitumor drug carrier. However, the effects of the cavity size and the spacer length on the carrier ability are not still known. In this study, we designed and evaluated the FA-appended three kinds of CyDs possessing a caproic acid as a spacer between FA and a CyD molecule (Fol-c(1)-CyDs) as a tumor targeting carrier for antitumor drugs. The stability constant of the Fol-c(1)-beta-CyD/doxorubicin (DOX) complex was much higher than those of Fol-c(1)-alpha-CyD and Fol-c(1)-gamma-CyD at pH 7.3. Antitumor activity of DOX was increased by the complexation with Fol-c(1)-beta-CyD, but not with Fol-c(1)-alpha-CyD or Fol-c(1)-gamma-CyD in KB cells, a folate receptor-alpha-positive cell line. Also, Fol-c(1)-beta-CyD increased antitumor activities of paclitaxel and vinblastine, but not 5-fluorouracil. Furthermore, Fol-c(1)-beta-CyD accelerated cellular uptake of DOX and inhibited its efflux from KB cells. The Fol-c(1)-beta-CyD/DOX complex showed much higher antitumor activity than DOX alone after intratumoral and intravenous administrations to tumor-bearing mice with a negligible change of the blood chemistry values. These findings suggest that Fol-c(1)-beta-CyD could be useful as a tumor-selective carrier for antitumor drugs.

  DOI：

  10.1021/bm401340g
• 作为产物：
  描述：

  hexakis(6-azido-6-deoxy)-α-cyclodextrin 在 ammonium hydroxide 、 三苯基膦 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 19.5h， 以70%的产率得到氨基-Α-环糊精
  参考文献：
  名称：

  Per(6-guanidino-6-deoxy)cyclodextrins: synthesis, characterisation and binding behaviour toward selected small molecules and DNA

  摘要：

  过(6-胍基-6-脱氧)-环糊精 4a、4b 和 4c 是新型衍生物，是在α-、β-和γ-环糊精的原边均匀引入胍基后得到的。这些产物是从相应的氨基衍生物中获得的，因为直接对已知的溴环糊精进行胍基化会产生混合物。通过核磁共振光谱和其他分析方法对新化合物进行了全面鉴定，并研究了它们与客体分子的相互作用。观察到了与 4-硝基苯磷酸（NPP）二钠盐的强络合（Kbinding ∼5 × 104 M-1），而与非磷酸化底物硝基苯（NB）形成的络合非常弱。二维 ROESY 光谱显示这两种情况下都存在空腔包合，但 NPP 的方向与 NB 相反，即磷酸基团朝向面向胍基团的一侧。4 对磷酸化客体具有很强的亲和力，这表明它有可能与 DNA 发生相互作用。研究发现，在琼脂糖凝胶电泳过程中，新化合物能完全抑制超纯小牛胸腺 DNA 的迁移，而单独使用胍基或普通环糊精则没有任何效果。此外，原子力显微镜还证明了 DNA 在 4b 的存在下凝结成纳米颗粒，证实了生物聚合物与多聚产物 4 之间强烈的静电相互作用。因此，4 和 DNA 之间强烈的胍磷酸盐相互作用归因于环糊精初级区域的胍基团聚集。空穴效应无法评估。

  DOI：

  10.1039/b614899a
• 作为试剂：
  描述：

  丙醛 、 丙酮 在 氨基-Α-环糊精 作用下， 以 水 为溶剂， 反应 6.0h， 以80%的产率得到a-D-核-六吡喃糖,2-脱氧-3-S-苯基-3-硫代-,三乙酸酯(9CI)
  参考文献：
  名称：

  在水相中催化不对称Aldol反应合成β-羟基羰基化合物的方法

  摘要：

  本发明公开了一种在水相中催化不对称Aldol反应合成β‑羟基羰基化合物的方法，其是在水相中，以全‑(6‑氨基)‑环糊精作为催化剂，在15℃～30℃下催化等摩尔量的酮与醛进行不对称Aldol反应，以高收率和高对映体过量值生成β‑羟基羰基化合物；本发明所述的全‑(6‑氨基)‑环糊精分别含有6、7和8个氨基葡萄糖单元，其空腔尺寸由小到大，可以容纳不同尺寸大小的底物；6‑位氨基一方面可通过共价作用活化底物，另一方面可作为氢键供体与底物形成氢键从而固定底物位置；该方法具有反应条件温和、收率高、对映选择性高、底物范围广等特点，在药物分子及其中间体的生产中具有较大的应用潜能。

  公开号：

  CN112266327B

文献信息

• Search for Cyclodextrin-Based Inhibitors of Anthrax Toxins: Synthesis, Structural Features, and Relative Activities
  作者：Vladimir A. Karginov、Ekaterina M. Nestorovich、Adiamseged Yohannes、Tanisha M. Robinson、Nour Eddine Fahmi、Frank Schmidtmann、Sidney M. Hecht、Sergey M. Bezrukov

  DOI：10.1128/aac.00693-06

  日期：2006.11

  Recently, using structure-inspired drug design, we demonstrated that aminoalkyl derivatives of β-cyclodextrin inhibited anthrax lethal toxin action by blocking the transmembrane pore formed by the protective antigen (PA) subunit of the toxin. In the present study, we evaluate a series of new β-cyclodextrin derivatives with the goal of identifying potent inhibitors of anthrax toxins. Newly synthesized hepta-6-thioaminoalkyl and hepta-6-thioguanidinoalkyl derivatives of β-cyclodextrin with alkyl spacers of various lengths were tested for the ability to inhibit cytotoxicity of lethal toxin in cells as well as to block ion conductance through PA channels reconstituted in planar bilayer lipid membranes. Most of the tested derivatives were protective against anthrax lethal toxin action at low or submicromolar concentrations. They also blocked ion conductance through PA channels at concentrations as low as 0.1 nM. The activities of the derivatives in both cell protection and channel blocking were found to depend on the length and chemical nature of the substituent groups. One of the compounds was also shown to block the edema toxin activity. It is hoped that these results will help to identify a new class of drugs for anthrax treatment, i.e., drugs that block the pathway for toxin translocation into the cytosol, the PA channel.

  摘要 最近，我们利用结构启发药物设计证明，β-环糊精的氨基烷基衍生物通过阻断炭疽毒素的保护性抗原（PA）亚基形成的跨膜孔来抑制炭疽致死毒素的作用。在本研究中，我们评估了一系列新的β-环糊精衍生物，目的是确定炭疽毒素的强效抑制剂。我们测试了新合成的具有不同长度烷基间隔的 β-环糊精庚-6-硫代氨基烷基和庚-6-硫代胍基烷基衍生物抑制细胞中致死毒素的细胞毒性以及阻断通过在平面双层脂膜中重建的 PA 通道的离子传导的能力。大多数受试衍生物在低浓度或亚摩尔浓度下对炭疽致死毒素的作用具有保护作用。它们还能在低至 0.1 nM 的浓度下阻断 PA 通道的离子传导。研究发现，这些衍生物在细胞保护和通道阻断方面的活性取决于取代基团的长度和化学性质。其中一种化合物还能阻断水肿毒素的活性。希望这些结果将有助于确定一类新的炭疽治疗药物，即阻断毒素转运到细胞膜的途径--PA 通道的药物。
• Per(6-guanidino-6-deoxy)cyclodextrins: synthesis, characterisation and binding behaviour toward selected small molecules and DNA
  作者：Nikolaos Mourtzis、Kyriaki Eliadou、Chrysie Aggelidou、Vassiliki Sophianopoulou、Irene M. Mavridis、Konstantina Yannakopoulou

  DOI：10.1039/b614899a

  日期：——

  Per(6-guanidino-6-deoxy)-cyclodextrins 4a, 4b and 4c are novel derivatives, resulting from homogeneous introduction of the guanidino group at the primary side of α-, β- and γ-cyclodextrins. The products were obtained from the corresponding amino derivatives, as direct guanidinylation of the known bromo-cyclodextrins provided mixtures. The new compounds were fully characterized by NMR spectroscopy and other analytical methods, and their interaction with guest molecules was studied. Strong complexation with 4-nitrophenyl phosphate (NPP) disodium salt was observed (Kbinding ∼5 × 104 M–1), whereas the non-phosphorylated substrate nitrobenzene (NB) formed a very weak complex. 2D ROESY spectra revealed cavity inclusion in both cases, however the orientation of NPP was opposite to that of NB, such that the phosphate group is oriented toward the primary side facing the guanidine groups. The strong affinity of 4 towards the phosphorylated guest suggested that interaction with DNA was possible. The new compounds were found to completely inhibit the migration of ultra pure calf thymus DNA during agarose gel electrophoresis, whereas no effects were observed with guanidine alone or with the plain cyclodextrins. Further, the condensation of DNA into nanoparticles in the presence of 4b was demonstrated by atomic force microscopy, confirming strong electrostatic interaction between the biopolymer and the multicationic products 4. The strong guanidine–phosphate interactions between 4 and DNA were therefore attributed to the clustering of the guanidine groups in the primary area of the cyclodextrin. Cavity effects could not be assessed.

  过(6-胍基-6-脱氧)-环糊精 4a、4b 和 4c 是新型衍生物，是在α-、β-和γ-环糊精的原边均匀引入胍基后得到的。这些产物是从相应的氨基衍生物中获得的，因为直接对已知的溴环糊精进行胍基化会产生混合物。通过核磁共振光谱和其他分析方法对新化合物进行了全面鉴定，并研究了它们与客体分子的相互作用。观察到了与 4-硝基苯磷酸（NPP）二钠盐的强络合（Kbinding ∼5 × 104 M-1），而与非磷酸化底物硝基苯（NB）形成的络合非常弱。二维 ROESY 光谱显示这两种情况下都存在空腔包合，但 NPP 的方向与 NB 相反，即磷酸基团朝向面向胍基团的一侧。4 对磷酸化客体具有很强的亲和力，这表明它有可能与 DNA 发生相互作用。研究发现，在琼脂糖凝胶电泳过程中，新化合物能完全抑制超纯小牛胸腺 DNA 的迁移，而单独使用胍基或普通环糊精则没有任何效果。此外，原子力显微镜还证明了 DNA 在 4b 的存在下凝结成纳米颗粒，证实了生物聚合物与多聚产物 4 之间强烈的静电相互作用。因此，4 和 DNA 之间强烈的胍磷酸盐相互作用归因于环糊精初级区域的胍基团聚集。空穴效应无法评估。
• Reddy, L. Rajender; Reddy, M. Arjun; Bhanumathi, Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2002, vol. 41, # 3, p. 645 - 646
  作者：Reddy, L. Rajender、Reddy, M. Arjun、Bhanumathi、Rama Rao

  DOI：——

  日期：——
• Binding of Phosphates to Aminocyclodextrin Biomimetics
  作者：Dragos Vizitiu、Gregory R. J. Thatcher

  DOI：10.1021/jo9902392

  日期：1999.8.1

  Aminocyclodextrins (ACDs) in which the primary face is perfacially substituted with amino pendant groups provide three potential biomimetic binding domains: the hydrophobic cavity, the cationic annulus, and the corona formed by the pendant tendrils. Binding of phosphate monoester dianions and diester monoanions by ACDs and native CDs is compared to that of neutral guest molecules. Binding to ACDs can be understood in terms of cooperativity between binding domains in which electrostatic and hydrophobic forces may be additive or compromised. Unexpectedly, slow chemical exchange is observed, in particular for dianionic aryl ester guest molecules. The substantial kinetic barriers for dissociation of these pseudorotaxane complexes are explained by the unfavorable passage of the anionic phosphate headgroup through the relatively hydrophobic ACD cavity.
• Design and Evaluation of Folate-Appended α-, β-, and γ-Cyclodextrins Having a Caproic Acid as a Tumor Selective Antitumor Drug Carrier in Vitro and in Vivo
  作者：Ayaka Okamatsu、Keiichi Motoyama、Risako Onodera、Taishi Higashi、Takahiro Koshigoe、Yasutaka Shimada、Kenjiro Hattori、Tomoko Takeuchi、Hidetoshi Arima

  DOI：10.1021/bm401340g

  日期：2013.12.9

  We reported that per-6-folic acid (FA)-appended beta-cyclodextrin (beta-CyD) possessing two caproic acids between FA and a beta-CyD molecule as a spacer (Fol-c(2)-beta-CyD) could be useful as a promising antitumor drug carrier. However, the effects of the cavity size and the spacer length on the carrier ability are not still known. In this study, we designed and evaluated the FA-appended three kinds of CyDs possessing a caproic acid as a spacer between FA and a CyD molecule (Fol-c(1)-CyDs) as a tumor targeting carrier for antitumor drugs. The stability constant of the Fol-c(1)-beta-CyD/doxorubicin (DOX) complex was much higher than those of Fol-c(1)-alpha-CyD and Fol-c(1)-gamma-CyD at pH 7.3. Antitumor activity of DOX was increased by the complexation with Fol-c(1)-beta-CyD, but not with Fol-c(1)-alpha-CyD or Fol-c(1)-gamma-CyD in KB cells, a folate receptor-alpha-positive cell line. Also, Fol-c(1)-beta-CyD increased antitumor activities of paclitaxel and vinblastine, but not 5-fluorouracil. Furthermore, Fol-c(1)-beta-CyD accelerated cellular uptake of DOX and inhibited its efflux from KB cells. The Fol-c(1)-beta-CyD/DOX complex showed much higher antitumor activity than DOX alone after intratumoral and intravenous administrations to tumor-bearing mice with a negligible change of the blood chemistry values. These findings suggest that Fol-c(1)-beta-CyD could be useful as a tumor-selective carrier for antitumor drugs.