6^II-^VII-hexa-O-methyl-6^I-O-propargylheptakis(2,3-di-O-methyl)cyclomaltoheptaose | 873090-08-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 6^II-^VII-hexa-O-methyl-6^I-O-propargylheptakis(2,3-di-O-methyl)cyclomaltoheptaose
• 英文别名: 6^II-VII-hexa-O-methyl-6^I-O-propargylheptakis(2,3-di-O-methyl)cyclomaltoheptaose；mono(6-O-propargyl) permethylated β-cyclodextrin；(1R,3R,5R,6R,8R,10R,11R,13R,15R,16R,18R,20R,21R,23R,25R,26R,28R,30R,31R,33R,35R,36S,37R,38S,39R,40S,41R,42S,43R,44S,45R,46S,47R,48S,49R)-36,37,38,39,40,41,42,43,44,45,46,47,48,49-tetradecamethoxy-5,10,15,20,30,35-hexakis(methoxymethyl)-25-(prop-2-ynoxymethyl)-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
• CAS: 873090-08-5
• 化学式: C₆₅H₁₁₂O₃₅
• 分子量: 1453.58
• InChiKey: MZSIGAAARZCHCT-IORFNPNNSA-N

物化性质

• 沸点：
  1132.2±65.0 °C(Predicted)
• 密度：
  1.27±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -3.6
• 重原子数：
  100
• 可旋转键数：
  29
• 环数：
  21.0
• sp3杂化的碳原子比例：
  0.97
• 拓扑面积：
  323
• 氢给体数：
  0
• 氢受体数：
  35

反应信息

• 作为反应物：
  描述：

  6^II-^VII-hexa-O-methyl-6^I-O-propargylheptakis(2,3-di-O-methyl)cyclomaltoheptaose 在 air 、 四甲基乙二胺 、 copper(l) chloride 作用下， 以 二氯甲烷 为溶剂， 反应 0.5h， 以52%的产率得到(1R,3R,5R,6R,8R,10R,11R,13R,15R,16R,18R,20R,21R,23R,25R,26R,28R,30R,31R,33R,35R,36S,37R,38S,39R,40S,41R,42S,43R,44S,45R,46S,47R,48S,49R)-36,37,38,39,40,41,42,43,44,45,46,47,48,49-tetradecamethoxy-5,10,15,20,30,35-hexakis(methoxymethyl)-25-[6-[[(1R,3R,5R,6R,8R,10R,11R,13R,15R,16R,18R,20R,21R,23R,25R,26R,28R,30R,31R,33R,35R,36S,37R,38S,39R,40S,41R,42S,43R,44S,45R,46S,47R,48S,49R)-36,37,38,39,40,41,42,43,44,45,46,47,48,49-tetradecamethoxy-5,15,20,25,30,35-hexakis(methoxymethyl)-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]nonatetracontan-10-yl]methoxy]hexa-2,4-diynoxymethyl]-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
  参考文献：
  名称：

  Acetylenic cyclodextrins for multireceptor architectures: cups with sticky ends for the formation of extension wires and junctions

  摘要：

  通过两种合成路线制备出了单-6-O-丙炔基过甲基化的 β-环糊精 3，它是一种多功能构筑基块，可用于构建具有潜在电子传导性核结的环糊精二聚体和三聚体。通过格拉塞-海耦合 3 得到了 β-环糊精二聚体 6，而通过钯（0）催化耦合则制备出了具有 1,4-亚苯基桥的环糊精二聚体 7 和基于 1,3,5-三取代苯的环糊精三聚体 8。 所有化合物都经过了全面的表征，特别是通过二维核磁共振光谱技术进行的详细分析为了解化合物的特性提供了有用的信息。此外，还介绍了单-3,6-脱水-庚基（2,3-O-甲基）-己基（6-O-甲基）-β-环糊精 5 的详细全面特性。产物 5 是在化合物 3 的甲基化过程中形成的，其形成对反应条件非常敏感。此外，还报告了与苯连接的二聚体 7 和三聚体 8 的吸收光谱和荧光光谱。它们显示了激发态的不同特性，这是因为苯烯核心施加了不同的电子耦合。

  DOI：

  10.1039/b508607h
• 作为产物：
  描述：

  2-丙炔-1-醇 、 [(1R,3R,5R,6R,8R,10R,11R,13R,15R,16R,18R,20R,21R,23R,25R,26R,28R,30R,31R,33R,35R,36S,37R,38S,39R,40S,41R,42S,43R,44S,45R,46S,47R,48S,49R)-36,37,38,39,40,41,42,43,44,45,46,47,48,49-tetradecamethoxy-5,15,20,25,30,35-hexakis(methoxymethyl)-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]nonatetracontan-10-yl]methyl 4-methylbenzenesulfonate 在 sodium hydride 作用下， 以89%的产率得到6^II-^VII-hexa-O-methyl-6^I-O-propargylheptakis(2,3-di-O-methyl)cyclomaltoheptaose
  参考文献：
  名称：

  使用环糊精标记的NHC金复合物在水中进行可持续的金催化

  摘要：

  描述了10种水溶性β-环糊精标记的NHC-gold（I）配合物的合成。关键步骤是亲核取代，以及铜（CuAAC）和钌（RuAAC）催化的叠氮化物炔烃环加成反应。尽管CuAAC可靠地提供了1,4-二取代的1,2,3-三唑，但RuAAC的区域选择性取决于偶联伙伴的结构。全甲基化环糊精标记的NHC金（I）复合物可溶于水和有机溶剂。在散装水中官能化的烯和炔烃的环化反应中，它们显示出出色的催化活性和可回收性。高达38％ee的γ-和δ-羟基丙二烯的对映选择性环异构化。因此，有可能利用环糊精部分的手性进行对映选择性金催化的转化。

  DOI：

  10.1002/cctc.201901658

文献信息

• The Impact of Heteromultivalency in Lectin Recognition and Glycosidase Inhibition: An Integrated Mechanistic Study
  作者：M. Isabel García-Moreno、Fernando Ortega-Caballero、Rocío Rísquez-Cuadro、Carmen Ortiz Mellet、José M. García Fernández

  DOI：10.1002/chem.201700470

  日期：2017.5.5

  between a protein receptor and its putative sugar ligand (glycotope) has proven too simplistic. On the one hand, binding of a glycotope in a dense glycocalix‐like construct to a lectin partner has been shown to be sensitive to the presence of a third sugar entity (heterocluster effect). On the other hand, several carbohydrate processing enzymes (glycosidases and glycosyltransferases) have been found

  事实证明，将多价视为限制蛋白受体与其假定的糖配体（糖基）之间亲和力增强的策略太简单了。一方面，已证明致密的糖杯状结构中的糖基与凝集素伴侣的结合对第三个糖实体的存在很敏感（杂簇效应）。另一方面，已经发现几种碳水化合物加工酶（糖苷酶和糖基转移酶）也对结合伴侣的多价呈递（多价酶抑制）有反应，这种现象最早是在亚氨基糖型抑制物种（抑制位）中发现的，最近被证明对多价碳水化合物构建体。通过评估结合α‐ d的一系列同构和异构簇与葡萄糖吡喃糖基相关的糖基和抗体表位显示，多价和异多价控制着这两种事件，从而以多峰方式允许针对多种凝集素和糖苷酶伴侣的特异性识别现象被激活，失活或增强。这种统一的情况源于（杂）多价架构触发糖苷酶结合模式的能力，这种模式让人联想到凝集素所利用的模式，在分析多价架构的生物学活性时应考虑这些因素。
• Pharmacological Chaperones for the Treatment of α-Mannosidosis
  作者：Rocío Rísquez-Cuadro、Reimi Matsumoto、Fernando Ortega-Caballero、Eiji Nanba、Katsumi Higaki、José Manuel García Fernández、Carmen Ortiz Mellet

  DOI：10.1021/acs.jmedchem.9b00153

  日期：2019.6.27

  alpha-Mannosidosis (AM) results from deficient lysosomal a-mannosidase (LAMAN) activity and subsequent substrate accumulation in the lysosome, leading to severe pathology. Many of the AM-causative mutations compromise enzyme folding and could be rescued with purpose-designed pharmacological chaperones (PCs). We found that PCs combining a LAMAN glycone-binding motif based on the 5N,6O-oxomethylidenemannojirimycin (OMJ) glycomimetic core and different aglycones, in either mono- or multivalent displays, elicit binding modes involving glycone and non-glycone enzyme regions that reinforce the protein folding and stabilization potential. Multivalent derivatives exhibited potent enzyme inhibition that generally prevailed over the chaperone effect. On the contrary, monovalent OMJ derivatives with LAMAN aglycone binding area-fitting substituents proved effective as activity enhancers for several mutant LAMAN forms in AM patient fibroblasts and/or transfected MAN2B1-KO cells. This translated into a significant improvement in endosomal/lysosomal function, reverting not only the primary LAMAN substrate accumulation but also the additional downstream consequences such as cholesterol accumulation.