Methyl 3,6-di-O-benzyl-2-O-[2-(methylsulfonyloxy)ethyl]-4-O-(2,3,4,6-tetra-O-benzyl-α-D-galactopyranosyl)-β-D-galactopyranoside | 345320-47-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: Methyl 3,6-di-O-benzyl-2-O-[2-(methylsulfonyloxy)ethyl]-4-O-(2,3,4,6-tetra-O-benzyl-α-D-galactopyranosyl)-β-D-galactopyranoside
• 英文别名: methyl 3,6-di-O-benzyl-4-O-(2,3,4,6-tetra-O-benzyl-α-D-galactopyranosyl)-2-O-(2-methylsulfonyloxyethyl)-β-D-galactopyranoside；2-[(2R,3R,4S,5S,6R)-2-methoxy-4-phenylmethoxy-6-(phenylmethoxymethyl)-5-[(2R,3R,4S,5S,6R)-3,4,5-tris(phenylmethoxy)-6-(phenylmethoxymethyl)oxan-2-yl]oxyoxan-3-yl]oxyethyl methanesulfonate
• CAS: 345320-47-0
• 化学式: C₅₈H₆₆O₁₄S
• 分子量: 1019.22
• InChiKey: GYTZNMQLWLAFMP-OFTXUDFNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.4
• 重原子数：
  73
• 可旋转键数：
  28
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  153
• 氢给体数：
  0
• 氢受体数：
  14

反应信息

• 作为反应物：
  描述：

  Methyl 3,6-di-O-benzyl-2-O-[2-(methylsulfonyloxy)ethyl]-4-O-(2,3,4,6-tetra-O-benzyl-α-D-galactopyranosyl)-β-D-galactopyranoside 在 sodium azide 、 四丁基碘化铵 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 以81%的产率得到methyl 3,6-di-O-benzyl-4-O-(2,3,4,6-tetra-O-benzyl-α-D-galactopyranosyl)-2-O-(2-azidoethyl)-β-D-galactopyranoside
  参考文献：
  名称：

  Optimization of Tether Length in Nonglycosidically Linked Bivalent Ligands That Target Sites 2 and 1 of a Shiga-like Toxin

  摘要：

  A series of bivalent ligands for a Shiga-like toxin have been synthesized, their experimentally determined inhibitory activities were compared with a simplified thermodynamic model, and computer simulations were used to predict the optimal tether length in bivalent ligands. The design of the inhibitors exploits the proximity of the C-2' hydroxyl groups of two P-k-trisaccharides when bound to two different, neighboring carbohydrate recognizing binding sites located on the surface of Shiga-like toxin. NMR studies of the complex between the toxin and bivalent ligands show that site 2 and site 1 of a single B subunit are simultaneously occupied by a tethered P-k-trisaccharide dimer. A simplified thermodynamic treatment provides the intrinsic affinities and binding energies for the intermolecular and intramolecular association events and permits the deconvolution of the contributions to the relative binding energies for the set of bivalent ligands. Conformational analysis based on MD simulations for bivalent galabioside dimers containing different tethers demonstrated that the calculated local concentrations of the pendant ligand at the second binding site correlate with the experimentally determined relative affinity values of the respective bivalent ligands, thereby providing a predictive method to optimize tether length.

  DOI：

  10.1021/ja0258529
• 作为产物：
  描述：

  在 吡啶 、 sodium tetrahydroborate 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 2.17h， 生成 Methyl 3,6-di-O-benzyl-2-O-[2-(methylsulfonyloxy)ethyl]-4-O-(2,3,4,6-tetra-O-benzyl-α-D-galactopyranosyl)-β-D-galactopyranoside
  参考文献：
  名称：

  志贺样毒素1型的二糖和三糖抑制剂的合成及其构效关系

  摘要：

  合成的半乳糖和P k-三糖类似物，其中选定的羟基被O-甲基取代，氨基 脱氧 乙酰氨基报道了脱氧和羧基烷基。这些的能力抑制剂通过固相竞争测定法评估阻断大肠杆菌维毒素1与其哺乳动物细胞表面受体的结合的方法。描述了用于该测定法的生物素化的糖缀合物的合成，其中构建了P k-三糖系链衍生物70并将其共价附接到牛血清白蛋白上，随后是生物素化。半乳糖衍生物4和5含有羧甲基β-半乳糖残基的O --2处的羧基或羧基乙基取代基显示出15-20倍的活性增加甲基糖苷半乳糖。对于相应的羧甲基取代的P k-三糖类似物13，未观察到这种增强的活性。通过与P k-三糖类似物复合的Verotoxin 1的晶体结构合理化抑制数据，并为二聚体的设计提供了见识抑制剂可以利用毒素B亚基的独特结合位点分布。该讨论提供了由有序人扮演的重要角色的另一个示例。水 糖中的分子蛋白质 复合体。

  DOI：

  10.1039/b009685g

文献信息

• Synthesis and structure–activity relationships of di- and trisaccharide inhibitors for Shiga-like toxin Type 1
  作者：Pavel I. Kitov、David R. Bundle

  DOI：10.1039/b009685g

  日期：——

  The syntheses of galabiose and Pk-trisaccharide analogues in which selected hydroxy groups are replaced by O-methyl, amino deoxy, acetamido deoxy, and carboxyalkyl groups are reported. The ability of these inhibitors to block E. coli verotoxin 1 binding to its mammalian cell-surface receptor are evaluated by a solid-phase competition assay. The synthesis of a biotinylated glycoconjugate for this assay

  合成的半乳糖和P k-三糖类似物，其中选定的羟基被O-甲基取代，氨基 脱氧 乙酰氨基报道了脱氧和羧基烷基。这些的能力抑制剂通过固相竞争测定法评估阻断大肠杆菌维毒素1与其哺乳动物细胞表面受体的结合的方法。描述了用于该测定法的生物素化的糖缀合物的合成，其中构建了P k-三糖系链衍生物70并将其共价附接到牛血清白蛋白上，随后是生物素化。半乳糖衍生物4和5含有羧甲基β-半乳糖残基的O --2处的羧基或羧基乙基取代基显示出15-20倍的活性增加甲基糖苷半乳糖。对于相应的羧甲基取代的P k-三糖类似物13，未观察到这种增强的活性。通过与P k-三糖类似物复合的Verotoxin 1的晶体结构合理化抑制数据，并为二聚体的设计提供了见识抑制剂可以利用毒素B亚基的独特结合位点分布。该讨论提供了由有序人扮演的重要角色的另一个示例。水 糖中的分子蛋白质 复合体。
• Optimization of Tether Length in Nonglycosidically Linked Bivalent Ligands That Target Sites 2 and 1 of a <i>Shiga</i>-like Toxin
  作者：Pavel I. Kitov、Hiroki Shimizu、Steven W. Homans、David R. Bundle

  DOI：10.1021/ja0258529

  日期：2003.3.1

  A series of bivalent ligands for a Shiga-like toxin have been synthesized, their experimentally determined inhibitory activities were compared with a simplified thermodynamic model, and computer simulations were used to predict the optimal tether length in bivalent ligands. The design of the inhibitors exploits the proximity of the C-2' hydroxyl groups of two P-k-trisaccharides when bound to two different, neighboring carbohydrate recognizing binding sites located on the surface of Shiga-like toxin. NMR studies of the complex between the toxin and bivalent ligands show that site 2 and site 1 of a single B subunit are simultaneously occupied by a tethered P-k-trisaccharide dimer. A simplified thermodynamic treatment provides the intrinsic affinities and binding energies for the intermolecular and intramolecular association events and permits the deconvolution of the contributions to the relative binding energies for the set of bivalent ligands. Conformational analysis based on MD simulations for bivalent galabioside dimers containing different tethers demonstrated that the calculated local concentrations of the pendant ligand at the second binding site correlate with the experimentally determined relative affinity values of the respective bivalent ligands, thereby providing a predictive method to optimize tether length.