Dimethyl (1S,2S,4S,5S)-4-(2-azidoethoxy)-5-(alpha-D-mannopyranosyloxy)cyclohexane-1,2-dicarboxylate | 948988-98-5

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: Dimethyl (1S,2S,4S,5S)-4-(2-azidoethoxy)-5-(alpha-D-mannopyranosyloxy)cyclohexane-1,2-dicarboxylate
• 英文别名: dimethyl (1S,2S,4S,5S)-4-(2-azidoethoxy)-5-[(2S,3S,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxycyclohexane-1,2-dicarboxylate
• CAS: 948988-98-5
• 化学式: C₁₈H₂₉N₃O₁₁
• 分子量: 463.442
• InChiKey: GYPSWCSPZCNQBY-JRFCXQANSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1
• 重原子数：
  32
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.89
• 拓扑面积：
  176
• 氢给体数：
  4
• 氢受体数：
  13

反应信息

• 作为反应物：
  描述：

  Dimethyl (1S,2S,4S,5S)-4-(2-azidoethoxy)-5-(alpha-D-mannopyranosyloxy)cyclohexane-1,2-dicarboxylate 在 palladium on carbon 氢气 作用下， 以 甲醇 为溶剂， 反应 1.0h， 以100%的产率得到dimethyl (1S,2S,4S,5S)-4-(2-aminoethoxy)-5-[(2S,3S,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxycyclohexane-1,2-dicarboxylate
  参考文献：
  名称：

  [EN] INHIBITORS OF MICROBIAL INFECTIONS
  [FR] INHIBITEURS D'INFECTIONS MICROBIENNES

  摘要：

  本发明适用于医学领域，特别是涉及用于治疗和/或预防HIV、埃博拉、登革热、丙型肝炎、SARS或结核感染的新化合物。

  公开号：

  WO2011000721A1
• 作为产物：
  描述：

  在 甲醇 、 sodium methylate 作用下， 反应 1.5h， 生成 Dimethyl (1S,2S,4S,5S)-4-(2-azidoethoxy)-5-(alpha-D-mannopyranosyloxy)cyclohexane-1,2-dicarboxylate
  参考文献：
  名称：

  带有C型凝集素的模拟糖文库的芯片上筛选显示了负责DC-SIGN / R和Langerin优先结合Dectin-2的结构特征

  摘要：

  合成了一个基于甘露糖和岩藻糖的糖模拟物库，并以微阵列格式针对一组包括DC-SIGN，DC-SIGNR，Langerin和dectin-2的C型凝集素受体（CLR）进行了筛选。首次鉴定出能够与dectin-2相互作用的拟模拟配体。结合概况的比较分析允许探测其对其他CLR的选择性。

  DOI：

  10.1002/chem.201802577

文献信息

• Efficient synthesis of phenylene-ethynylene rods and their use as rigid spacers in divalent inhibitors
  作者：Francesca Pertici、Norbert Varga、Arnoud van Duijn、Matias Rey-Carrizo、Anna Bernardi、Roland J Pieters

  DOI：10.3762/bjoc.9.25

  日期：——

  phenylene-ethynylene rods and their use as rigid spacers is described. Alternation of a Sonogashira reaction and silyl group cleavage was used to obtain rigid spacers with even and odd numbers of phenylene units. Preliminary applications of these rods in divalent systems are shown. Inhibition studies with Pseudomonas Aeruginosa lectin LecA showed that the rigid spacer proved greatly beneficial for the

  描述了亚苯基-乙炔棒的合成及其作为刚性垫片的用途。Sonogashira 反应和甲硅烷基裂解的交替用于获得具有偶数和奇数亚苯基单元的刚性间隔物。显示了这些杆在二价系统中的初步应用。铜绿假单胞菌凝集素 LecA 的抑制研究表明，刚性间隔物证明对抑制效力非常有益。
• Inhibitors of microbial infections
  申请人：Universita' degli Studi di Milano

  公开号：EP2289904A1

  公开（公告）日：2011-03-02

  The present invention finds application in the field of medicine and, in particular, it relates to new compounds for the treatment and/or prevention of HIV; Ebola, Dengue, Hepatitis C, SARS or tuberculosis infections.

  本发明适用于医学领域，特别是涉及用于治疗和/或预防HIV，埃博拉，登革热，丙型肝炎，SARS或结核感染的新化合物。
• Designing nanomolar antagonists of DC-SIGN-mediated HIV infection: ligand presentation using molecular rods
  作者：Stefania Ordanini、Norbert Varga、Vanessa Porkolab、Michel Thépaut、Laura Belvisi、Andrea Bertaglia、Alessandro Palmioli、Angela Berzi、Daria Trabattoni、Mario Clerici、Franck Fieschi、Anna Bernardi

  DOI：10.1039/c4cc09709b

  日期：——

  Rational design of DC-SIGN antagonists combines a selective glycomimetic ligand with trivalent dendrons spaced by a rigid core and allows to exploit multiple multivalency effects.

  DC-SIGN拮抗剂的合理设计将选择性的糖类拟合体配合刚性核心的三价树状分子结合起来，从而利用多重多价效应。
• Structure of a Glycomimetic Ligand in the Carbohydrate Recognition Domain of C-type Lectin DC-SIGN. Structural Requirements for Selectivity and Ligand Design
  作者：Michel Thépaut、Cinzia Guzzi、Ieva Sutkeviciute、Sara Sattin、Renato Ribeiro-Viana、Norbert Varga、Eric Chabrol、Javier Rojo、Anna Bernardi、Jesus Angulo、Pedro M. Nieto、Franck Fieschi

  DOI：10.1021/ja3053305

  日期：2013.2.20

  In genital mucosa, different fates are described for HIV according to the subtype of dendritic cells (DCs) involved in its recognition. This notably depends on the C-type lectin receptor, langerin or DC-SIGN, involved in gp120 interaction. Langerin blocks HIV transmission by its internalization in specific organelles of Langerhans cells. On the contrary, DC-SIGN enhances HIV trans-infection of T lymphocytes. Thus, approaches aiming to inhibit DC-SIGN, without blocking langerin, represent attractive anti-HIV strategies. We previously demonstrated that dendrons bearing multiple copies of glycomimetic compounds were able to block DC-SIGN-dependent HIV infection in cervical explant models. Optimization of such ligand requires detailed characterization of its binding mode. In the present work, we determined the first high-resolution structure of a glycomimetic/DC-SIGN complex by X-ray crystallography. This glycomimetic, pseudo-1,2-mannobioside, shares shape and conformational properties with Manα1-2Man, its natural counterpart. However, it uses the binding epitope previously described for Lewis X, a ligand specific for DC-SIGN among the C-type lectin family. Thus, selectivity gain for DC-SIGN versus langerin is observed with pseudo-1,2-mannobioside as shown by surface plasmon resonance analysis. In parallel, ligand binding was also analyzed by TR-NOESY and STD NMR experiments, combined with the CORCEMA-ST protocol. These studies demonstrate that the complex, defined by X-ray crystallography, represents the unique binding mode of this ligand as opposed to the several binding orientations described for the natural ligand. This exclusive binding mode and its selective interaction properties position this glycomimetic as a good lead compound for rational improvement based on a structurally driven approach.
• On-Chip Screening of a Glycomimetic Library with C-Type Lectins Reveals Structural Features Responsible for Preferential Binding of Dectin-2 over DC-SIGN/R and Langerin
  作者：Laura Medve、Silvia Achilli、Sonia Serna、Fabio Zuccotto、Norbert Varga、Michel Thépaut、Monica Civera、Corinne Vivès、Franck Fieschi、Niels Reichardt、Anna Bernardi

  DOI：10.1002/chem.201802577

  日期：2018.9.25

  A library of mannose‐ and fucose‐based glycomimetics was synthesized and screened in a microarray format against a set of C‐type lectin receptors (CLRs) that included DC‐SIGN, DC‐SIGNR, langerin, and dectin‐2. Glycomimetic ligands able to interact with dectin‐2 were identified for the first time. Comparative analysis of binding profiles allowed their selectivity against other CLRs to be probed.

  合成了一个基于甘露糖和岩藻糖的糖模拟物库，并以微阵列格式针对一组包括DC-SIGN，DC-SIGNR，Langerin和dectin-2的C型凝集素受体（CLR）进行了筛选。首次鉴定出能够与dectin-2相互作用的拟模拟配体。结合概况的比较分析允许探测其对其他CLR的选择性。