全氨基倍他环糊精 | 30754-24-6

• 物质功能分类: 生物化工 - 糖类化合物 - 多糖
• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 全氨基倍他环糊精
• 英文名称: heptakis(6-amino-6-deoxy)-β-cyclodextrin
• 英文别名: heptakis(6-amino-6-deoxy)-β-CD；Per-6-amino-beta-cyclodextrin；(1S,3R,5R,6S,8R,10R,11S,13R,15R,16S,18R,20R,21S,23R,25R,26S,28R,30R,31S,33R,35R,36R,37R,38R,39R,40R,41R,42R,43R,44R,45R,46R,47R,48R,49R)-5,10,15,20,25,30,35-heptakis(aminomethyl)-2,4,7,9,12,14,17,19,22,24,27,29,32,34-tetradecaoxaoctacyclo[31.2.2.23,6.28,11.213,16.218,21.223,26.228,31]nonatetracontane-36,37,38,39,40,41,42,43,44,45,46,47,48,49-tetradecol
• CAS: 30754-24-6
• 化学式: C₄₂H₇₇N₇O₂₈
• 分子量: 1128.1
• InChiKey: GOPKBPURTDZYDJ-FOUAGVGXSA-N

物化性质

• 熔点：
  208 °C
• 沸点：
  1453.9±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)：
  -16.8
• 重原子数：
  77
• 可旋转键数：
  7
• 环数：
  21.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  595
• 氢给体数：
  21
• 氢受体数：
  35

反应信息

• 作为反应物：
  描述：

  Lactose 、 全氨基倍他环糊精 在 sodium cyanoborohydride 作用下， 以 二甲基亚砜 为溶剂， 反应 24.0h， 以25%的产率得到
  参考文献：
  名称：

  Synthesis of multi-lactose-appended β-cyclodextrin and its cholesterol-lowering effects in Niemann–Pick type C disease-like HepG2 cells

  摘要：

  尼曼-匹克C型（NPC）疾病，由于NPC1和NPC2两种蛋白质的缺陷导致细胞内游离胆固醇和其他脂质的积累，引起神经退行性和其他致命的神经内脏症状。目前，治疗NPC疾病涉及使用2-羟丙基-β-环糊精（HP-β-CD）。HP-β-CD在治疗NPC疾病中对肝脾肿大有效，尽管需要非常高的剂量。减少治疗NPC所需HP-β-CD剂量的一种方法是通过β-环糊精（β-CD）积极靶向肝细胞。本研究的目的是合成一种新型多乳糖附加的β-环糊精（multi-Lac-β-CD），并评估其在U18666A处理的HepG2（类NPC HepG2）细胞中的降胆固醇效果。此外，研究旨在通过胆固醇积聚的HepG2细胞将β-CD传递给肝细胞，并指出新合成的多乳糖附加的β-CD的乳糖取代度（DSL）平均为5.6。发现这种新合成的多乳糖附加的β-CD与HP-β-CD相比，显著降低了细胞内胆固醇浓度，并且毒性微乎其微。在类NPC HepG2细胞中观察到TRITC-多乳糖附加的β-CD（DSL 5.6）与TRITC-HP-β-CD相比的增加内化。此外，发现多乳糖附加的β-CD（DSL5.6）与花生凝集素的解离常数极低（2.5×10⁻⁸ M）。这些结果表明，多乳糖附加的β-CD（DSL5.6）通过非糖蛋白受体（ASGPR）介导的内吞作用降低了类NPC HepG2细胞内胆固醇水平。

  DOI：

  10.3762/bjoc.13.2
• 作为产物：
  描述：

  七(6-溴-6-脱氧)-beta-环糊精 在 氨 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 全氨基倍他环糊精
  参考文献：
  名称：

  Cell transfection with polycationic cyclodextrin vectors

  摘要：

  Polycationic cyclodextrins (CDs) were complexed with plasmid DNA and their effectiveness as vectors was tested on COS-7 cells. These CDs were modified with pyridylamino, alkylimidazole, methoxyethylamino or primary amine groups at 6-positions of the glucose units. Uncharged CDs, beta-CD, hydroxypropyl-beta-CD, and dimethyl-beta-CD were also tested, but these did not form stable complexes with the DNA and produced only a slight improvement in transfection level over DNA alone. The polycationic CDs neutralised DNA to form stable nanoparticulate complexes. The transfection efficiency of these CDs was dependent on the substituents present, with the most efficient having either an amino, pyridylamino or butylimidazole group at the 6-positions and unmodified 2- and 3-hydroxyls. One of the most effective vectors, heptakispyridylamino CD, produced a 4000-fold increase in transfection level over DNA alone. Levels were improved 10-fold by use of the endosomolytic agent, chloroquine. The transfection efficiency of the best of these systems in serum equals that of DOTAP in serum. Studies with P-32-labelled plasmid DNA indicate that the polycationic CDs are exceptional promoters of DNA cellular-uptake, the most efficient surpassing DOTAP. Uptake is dependent on proteoglycan-mediated binding to cells. The data imply that intracellular trafficking but not cellular uptake, may be the rate-limiting step in the transfection process. These initial results indicate that CDs are useful templates for further modification to produce molecular constructs capable of enhanced gene delivery. (C) 2004 Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.ejps.2004.01.001
• 作为试剂：
  描述：

  反式肉桂醛 、 硝基甲烷 在 全氨基倍他环糊精 作用下， 以 水 、 丙酮 、 乙腈 为溶剂， 反应 7.0h， 生成 (2S,3E)-1-nitro-4-phenylbut-3-en-2-ol 、 (R)-(E)-1-nitro-4-phenylbut-3-en-2-ol
  参考文献：
  名称：

  Per-6-amino-β-cyclodextrin as a Reusable Promoter and Chiral Host for Enantioselective Henry Reaction

  摘要：

  A highly efficient enantioselective Henry reaction has been carried out using per-6-ABCD as a supramolecular chiral host and promoter to give the corresponding adduct with high yield (up to 99%) and enantiomeric excess (up to 99%). Per-6-ABCD also promotes the diastereoselective Henry reaction in a syn-selective manner to give the adduct up to 99% yield with 99:1 syn/anti selectivity. The enantiomeric excess of the syn-adduct is 99%. The catalyst is recovered and reused without loss in its activity.

  DOI：

  10.1021/ol101658n

文献信息

• Inclusion of chemotherapeutic agents in substituted β-cyclodextrin derivatives
  作者：Carolin Thiele、Dagmar Auerbach、Gregor Jung、Gerhard Wenz

  DOI：10.1007/s10847-010-9741-4

  日期：2011.4

  The stabilities of the inclusion compounds of three chemotherapeutic agents, camptothecin (CPT), docetaxel (DOC) and idarubicin (IDA), plus a model compound 1,4-dihydroxyanthraquinone (DHA) with several β-cyclodextrin (β-CD) derivatives were investigated by solubility measurements, isothermal titration microcalorimetry and fluorescence anisotropy measurements. Ionic heptakis-(6-deoxy-6-thioethers)

  三种化学治疗剂喜树碱 (CPT)、多西他赛 (DOC) 和伊达比星 (IDA) 的包合物以及模型化合物 1,4-二羟基蒽醌 (DHA) 与几种 β-环糊精 (β-CD) 衍生物的稳定性分别为通过溶解度测量、等温滴定微量热法和荧光各向异性测量进行研究。发现 β-CD 的离子七-（6-脱氧-6-硫醚）对这些药物表现出非常高的结合潜力，使它们成为先进药物递送的良好候选者。
• Ultrasensitive QRS made by supramolecular assembly of functionalized cyclodextrins and graphene for the detection of lung cancer VOC biomarkers
  作者：Sananda Nag、Lisday Duarte、Emilie Bertrand、Véronique Celton、Mickaël Castro、Veena Choudhary、Philippe Guegan、Jean-François Feller

  DOI：10.1039/c4tb01041h

  日期：——

  A novel electronic nose system comprising functionalized β-cyclodextrin wrapped reduced graphene oxide (RGO) sensors with distinct ability of discrimination of a set of volatile organic compounds has been developed. Non-covalent modification of chemically functionalized cyclodextrin with RGO is carried out by using pyrene adamantane as a linker wherever necessary, in order to construct a supramolecular

  已经开发了一种新型的电子鼻系统，该系统包括功能化的β-环糊精包裹的还原型氧化石墨烯（RGO）传感器，该传感器具有区分一组挥发性有机化合物的独特能力。在必要时，通过使用pyr金刚烷作为连接基，用RGO对化学官能化的环糊精进行非共价修饰，以构建超分子组装体。利用环糊精的选择性化学修饰原理改变环糊精上的化学官能度。在本研究中，主体-客体包合物的形成能力和环糊精的可调化学功能以及石墨烯的高表面积和电导率的综合优势，
• Recognition of Ionic Guests by Ionic β-Cyclodextrin Derivatives
  作者：Gerhard Wenz、Christian Strassnig、Carolin Thiele、Annegret Engelke、Bernd Morgenstern、Kaspar Hegetschweiler

  DOI：10.1002/chem.200800295

  日期：2008.8.18

  Inclusion compounds of cationic, anionic, and neutral p-substituted derivatives of tert-butylbenzene complexed in beta-cyclodextrin and its ionic 6-mono and 6-hepta derivatives were systematically investigated by isothermal titration calorimetry (ITC). All inclusion compounds showed 1:1 stoichiometry with binding constants ranging from 10 to 3 x 10(6) M(-1). The binding free energies could be subdivided

  通过等温滴定量热法（ITC）系统地研究了络合在β-环糊精中的叔丁基苯的阳离子，阴离子和中性对位取代衍生物的包合物。所有包含化合物均显示1：1的化学计量比，结合常数范围为10到3 x 10（6）M（-1）。结合自由能可细分为非极性和静电贡献。静电相互作用可以根据库仑定律通过考虑主体和客体的质子化程度，主体内客体的方向以及Debye-Huckel-Onsager理论描述的离子屏蔽来定量描述。客体在环糊精腔内的取向通过ROESY NMR光谱法确定。
• Self-Assembly PEGylation Retaining Activity (SPRA) Technology via a Host–Guest Interaction Surpassing Conventional PEGylation Methods of Proteins
  作者：Tatsunori Hirotsu、Taishi Higashi、Irhan Ibrahim Abu Hashim、Shogo Misumi、Koki Wada、Keiichi Motoyama、Hidetoshi Arima

  DOI：10.1021/acs.molpharmaceut.6b00678

  日期：2017.2.6

  Polyethylene glycol (PEG) modification (PEGylation) is one of the best approaches to improve the stabilities and blood half-lives of protein drugs; however, PEGylation dramatically reduces the bioactivities of protein drugs. Here, we present “self-assembly PEGylation retaining activity” (SPRA) technology via a host–guest interaction between PEGylated β-cyclodextrin (PEG-β-CyD) and adamantane-appended

  聚乙二醇（PEG）修饰（PEGylation）是提高蛋白质药物的稳定性和血液半衰期的最佳方法之一；然而，聚乙二醇化极大地降低了蛋白质药物的生物活性。在这里，我们通过聚乙二醇化的β-环糊精（PEG-β-CyD）与金刚烷附加的（Ad）蛋白之间的客体相互作用，提出了“自组装聚乙二醇化保留活性”（SPRA）技术。PEG-β-CyD与Ad-胰岛素和Ad-溶菌酶形成稳定的复合物，分别产生SPRA-胰岛素和SPRA-溶菌酶。两种SPRA蛋白均显示出对热和胰蛋白酶消化的高稳定性，与共价PEG化的蛋白当量相当。重要的是，SPRA溶菌酶拥有约。裂解活性为100％，而共价聚乙二醇化溶菌酶的活性为。23％。此外，与甘精胰岛素相比，SPRA-胰岛素提供了延长且无峰的血糖分布。它也没有显示出活动的损失。相反，共价聚乙二醇化的胰岛素显示出微不足道的降血糖作用。这些发现表明，SPRA技术有潜力作为一种通用方法，超越了蛋白质的常规PEG化方法。
• 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。