1-(11-amino-3,6,9-trioxa-undecyl)-2,3,4,6-tetra-O-acetyl-O-α-D-mannopyranoside | 236092-97-0

• 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: 1-(11-amino-3,6,9-trioxa-undecyl)-2,3,4,6-tetra-O-acetyl-O-α-D-mannopyranoside
• 英文别名: [(2R,3R,4S,5S,6S)-3,4,5-triacetyloxy-6-[2-[2-[2-(2-aminoethoxy)ethoxy]ethoxy]ethoxy]oxan-2-yl]methyl acetate
• CAS: 236092-97-0
• 化学式: C₂₂H₃₇NO₁₃
• 分子量: 523.535
• InChiKey: DBKLMBNDLYJDFR-AANPDWTMSA-N

物化性质

• 沸点：
  567.3±50.0 °C(Predicted)
• 密度：
  1.24±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.8
• 重原子数：
  36
• 可旋转键数：
  21
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  177
• 氢给体数：
  1
• 氢受体数：
  14

反应信息

• 作为反应物：
  描述：

  1-(11-amino-3,6,9-trioxa-undecyl)-2,3,4,6-tetra-O-acetyl-O-α-D-mannopyranoside 在 水 、 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 、 三苯基膦 作用下， 以 四氢呋喃 为溶剂， 生成
  参考文献：
  名称：

  新型甘露糖苷糖脂缀合物的抑制HIV-1反式感染。

  摘要：

  结合有甘露糖的凝集素，例如树突状细胞特异性的ICAM-3吞噬非整联蛋白（DC-SIGN），在人类树突状细胞（DC）的表面表达，这些树突状细胞捕获并传播1型人类免疫缺陷病毒（HIV- 1）到CD4 +细胞。目的是减少病毒的反式-通过靶向DC-SIGN进行感染，我们设计了一种新型的甘露糖苷糖脂结合物。我们报告了由甘露糖头，对水性介质溶解性必不可少的亲水性连接基和可变长度的脂链组成的两亲物的合成。这些结合物基于甘露糖苷头部和脂质链之间的相互作用而呈现出不同寻常的特性，从而增强了亲和力并降低了对多价的需求。以最佳脂质长度，它们表现出对DC-SIGN的强结合亲和力（K d在微摩尔范围内），通过表面等离振子共振评估。活性最高的分子是分支的甜菊糖苷结合物，能够抑制HIV-1包膜与DC的相互作用，并大幅度降低反式-DC介导的HIV-1感染（IC 50s在低微摩尔范围内）。这类新化合物可能具有预防HIV-1

  DOI：

  10.1021/bc200644d
• 作为产物：
  描述：

  11-叠氮基-3,6,9-三氧杂十一醇 在 三氟甲磺酸三甲基硅酯 、 水 、 三苯基膦 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 生成 1-(11-amino-3,6,9-trioxa-undecyl)-2,3,4,6-tetra-O-acetyl-O-α-D-mannopyranoside
  参考文献：
  名称：

  新型甘露糖苷糖脂缀合物的抑制HIV-1反式感染。

  摘要：

  结合有甘露糖的凝集素，例如树突状细胞特异性的ICAM-3吞噬非整联蛋白（DC-SIGN），在人类树突状细胞（DC）的表面表达，这些树突状细胞捕获并传播1型人类免疫缺陷病毒（HIV- 1）到CD4 +细胞。目的是减少病毒的反式-通过靶向DC-SIGN进行感染，我们设计了一种新型的甘露糖苷糖脂结合物。我们报告了由甘露糖头，对水性介质溶解性必不可少的亲水性连接基和可变长度的脂链组成的两亲物的合成。这些结合物基于甘露糖苷头部和脂质链之间的相互作用而呈现出不同寻常的特性，从而增强了亲和力并降低了对多价的需求。以最佳脂质长度，它们表现出对DC-SIGN的强结合亲和力（K d在微摩尔范围内），通过表面等离振子共振评估。活性最高的分子是分支的甜菊糖苷结合物，能够抑制HIV-1包膜与DC的相互作用，并大幅度降低反式-DC介导的HIV-1感染（IC 50s在低微摩尔范围内）。这类新化合物可能具有预防HIV-1

  DOI：

  10.1021/bc200644d

文献信息

• Mannosylated compounds useful for the prevention and the treatment of infectious diseases
  申请人：Université de Strasbourg

  公开号：EP2594575A1

  公开（公告）日：2013-05-22

  The present invention relates to new anti-infectious compounds consisting of (i) a polar head having from one to three mannose, dimannose or trimannose moieties, which is coupled through an appropriate linker to (ii) a single lipid chain of at least 17 carbon atoms of length. Pharmaceutical compositions and therapeutic uses thereof are also provided.

  本发明涉及由（i）具有一到三个甘露糖、二甘露糖或三甘露糖基团的极性头部与（ii）至少含有17个碳原子长度的单脂肪链通过适当的连接剂耦合而成的新型抗感染化合物。同时提供了药物组合物及其治疗用途。
• Directed Interactions of Block Copolypept(o)ides with Mannose-binding Receptors: PeptoMicelles Targeted to Cells of the Innate Immune System
  作者：Philipp Heller、Nicole Mohr、Alexander Birke、Benjamin Weber、Angelika Reske-Kunz、Matthias Bros、Matthias Barz

  DOI：10.1002/mabi.201400417

  日期：2015.1

  acid N‐carboxyanhydrides. These amphiphilic block copolypept(o)ides self‐assemble into multivalent PeptoMicelles and bind to mannose‐binding receptors as expressed by dendritic cells. Mannosylated micelles showed enhanced cell uptake in DC 2.4 cells and in bone marrow‐derived dendritic cells (BMDCs) and therefore appear to be a suitable platform for immune modulation.

  基于多肽（o）化物的核-壳结构将电晕物质聚肌氨酸的隐身性与多肽核的可调节功能相结合。含甘露糖的嵌段共多肽（PSar-block-PGlu（OBn））已使用11-氨基-3,6,9-三氧杂-十一烷基-2,3,4,6-四-O-乙酰基合成-α-α-D-甘露吡喃糖苷作为引发剂在α-氨基酸N-羧基酸酐的连续开环聚合中。这些两亲性嵌段共聚肽（o）化物自组装成多价PeptoMicelles，并与树突状细胞表达的甘露糖结合受体结合。甘露糖基化的胶束在DC 2.4细胞和骨髓源性树突状细胞（BMDC）中显示出增强的细胞摄取，因此似乎是进行免疫调节的合适平台。
• [EN] MANNOSYLATED COMPOUNDS USEFUL FOR THE PREVENTION AND THE TREATMENT OF INFECTIOUS DISEASES<br/>[FR] COMPOSÉS MANNOSYLÉS UTILISÉS DANS LA PRÉVENTION ET LE TRAITEMENT DE MALADIES INFECTIEUSES
  申请人：UNIV STRASBOURG

  公开号：WO2013072355A1

  公开（公告）日：2013-05-23

  The present invention relates to new anti-infectious compounds consisting of (i) a polar head having from one to three mannose, dimannose or trimannose moieties, which is coupled through an appropriate linker to (ii) a single lipid chain of at least 17 carbon atoms of length. Pharmaceutical compositions and therapeutic uses thereof are also provided.

  本发明涉及由(i) 一个具有一个到三个甘露糖、二甘露糖或三甘露糖基团的极性头部，通过适当的连接剂连接到(ii) 至少含有17个碳原子长度的单一脂肪链的新型抗感染化合物。同时提供了药物组合物和治疗用途。
• A comparison of biological and calorimetric analyses of multivalent glycodendrimer ligands for concanavalin A
  作者：Jayme B. Corbell、Joseph J. Lundquist、Eric J. Toone

  DOI：10.1016/s0957-4166(99)00589-3

  日期：2000.1

  The cluster glycoside effect - the observation that multivalent glycosides bind to their polyvalent protein receptors with apparent affinities greater than those that can be rationalized solely on the basis of valency is by now a well established phenomenon. As part of a continuing effort to provide a molecular basis for the cluster glycoside effect, we report here the synthesis of two series of mannosylated dendritic ligands and their performance in a range of competitive and non-competitive binding assays, including hemeagglutination inhibition (HIA), enzyme-linked lectin assays (ELLA) and isothermal titration microcalorimetry (ITC). The first series of ligands contained a semi-rigid glycylglycine spacer and showed no significant performance enhancement in any binding studies. The second series of ligands contained a flexible tetraethylene glycol spacer; these ligands showed marked enhancements at tetravalent and hexavalent levels in both HIA (IC50=3 and <0.8 mu M, respectively) and ITC (K-A=6.2x10(4) and 1.5x10(6) M-1, respectively) studies. In all cases, the thermodynamic parameters of association are consistent with non-specific aggregation rather than enhanced lectin-ligand affinity. This conclusion is reinforced by the lack of enhancements in ligand activity observed in ELLA studies. (C) 2000 Elsevier Science I;td. All rights reserved.
• Dynamic Micelles of Mannoside Glycolipids are more Efficient than Polymers for Inhibiting HIV-1 <i>trans</i>-Infection
  作者：Evelyne Schaeffer、Laure Dehuyser、David Sigwalt、Vincent Flacher、Serena Bernacchi、Olivier Chaloin、Jean-Serge Remy、Christopher G. Mueller、Rachid Baati、Alain Wagner

  DOI：10.1021/bc4000806

  日期：2013.11.20

  Mannoside glycolipid conjugates are able to inhibit human immunodeficiency virus type 1 (HIV-1) trans-infection mediated by human dendritic cells (DCs). The conjugates are formed by three building blocks: a linear or branched mannose head, a hydrophilic linker, and a 24-carbon lipid chain. We have shown that, even as single molecules, these compounds efficiently target mannose-binding lectins, such as DC-specific ICAM-3-grabbing nonintegrin (DC-SIGN) important for HIV-1 transmission. With the goal to optimize their inhibitory activity by supramolecular structure formation, we have compared saturated and unsaturated conjugates, as single molecules, self-assemblies of dynamic micelles, and photopolymerized cross-linked polymers. Surface plasmon resonance showed that, unexpectedly, polymers of trivalent conjugates did not display a higher binding affinity for DC-SIGN than single molecules. Interactions on a chip or in solution were independent of calcium; however, binding to DCs was inhibited by a calcium chelator. Moreover, HIV-1 trans-infection was mostly inhibited by dynamic micelles and not by rigid polymers. The inhibition data revealed a clear correlation between the structure and molecular assembly of a conjugate and its biological antiviral activity. We present an interaction model between DC-SIGN and conjugates-either single molecules, micelles, or polymers-that highlights that the most effective interactions by dynamic micelles involve both mannose heads and lipid chains. Our data reveal that trivalent glycolipid conjugates display the highest microbicide potential for HIV prophylaxis, as dynamic micelles conjugates and not as rigid polymers.