(2S,3S)-4-[[(2S,3S,4R)-2-amino-3,4-dihydroxyoctadecyl]oxy]butane-1,2,3-triol | 1169412-26-3

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: (2S,3S)-4-[[(2S,3S,4R)-2-amino-3,4-dihydroxyoctadecyl]oxy]butane-1,2,3-triol
• 英文别名: (2S,3S)-4-[(2S,3S,4R)-2-amino-3,4-dihydroxyoctadecoxy]butane-1,2,3-triol
• CAS: 1169412-26-3
• 化学式: C₂₂H₄₇NO₆
• 分子量: 421.618
• InChiKey: VMEDZIMVKKBPEN-WIYBCGNWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.86
• 重原子数：
  29.0
• 可旋转键数：
  21.0
• 环数：
  0.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  136.4
• 氢给体数：
  6.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  [14C]hexacosanoic acid chloride 、 (2S,3S)-4-[[(2S,3S,4R)-2-amino-3,4-dihydroxyoctadecyl]oxy]butane-1,2,3-triol 在 sodium acetate 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 2.0h， 以85%的产率得到Thr[14C]Cer
  参考文献：
  名称：

  苏糖醇神经酰胺和[ 14 C]苏糖醇神经酰胺的合成，强力CD1d抗原α-半乳糖基神经酰胺的非糖苷类似物

  摘要：

  描述了苏糖醇神经酰胺的合成，它是有效的CD1d抗原α-半乳糖基神经酰胺的非糖苷类似物。还提出了14 C标记的苏糖醇神经酰胺类似物的合成。这种放射性标记的类似物将允许研究此iNKT-CD1d细胞激动剂的细胞内运输模式/端粒。

  DOI：

  10.1016/j.tetasy.2009.02.020
• 作为产物：
  描述：

  [(4S,5S)-5-[[(2S)-2-azido-2-[(4S,5R)-2,2-dimethyl-5-tetradecyl-1,3-dioxolan-4-yl]ethoxy]methyl]-2-phenyl-1,3-dioxolan-4-yl]methanol 在 cerium triflate 、 palladium on activated charcoal 、 氢气 、 溶剂黄146 作用下， 以 硝基甲烷 、 二氯甲烷 、 甲醇 为溶剂， 反应 4.0h， 以50%的产率得到(2S,3S)-4-[[(2S,3S,4R)-2-amino-3,4-dihydroxyoctadecyl]oxy]butane-1,2,3-triol
  参考文献：
  名称：

  苏糖醇神经酰胺和[ 14 C]苏糖醇神经酰胺的合成，强力CD1d抗原α-半乳糖基神经酰胺的非糖苷类似物

  摘要：

  描述了苏糖醇神经酰胺的合成，它是有效的CD1d抗原α-半乳糖基神经酰胺的非糖苷类似物。还提出了14 C标记的苏糖醇神经酰胺类似物的合成。这种放射性标记的类似物将允许研究此iNKT-CD1d细胞激动剂的细胞内运输模式/端粒。

  DOI：

  10.1016/j.tetasy.2009.02.020

文献信息

• [EN] COMPOUNDS FOR ACTIVATING INVARIANT NATURAL KILLER T-CELLS AND METHODS OF USE IN ELIMINATING INFLAMMATORY SENESCENT CELLS<br/>[FR] COMPOSÉS POUR ACTIVER DES LYMPHOCYTES T TUEURS NATURELS INVARIANTS ET MÉTHODES D'UTILISATION DANS L'ÉLIMINATION DE CELLULES SÉNESCENTES INFLAMMATOIRES
  申请人：DECIDUOUS THERAPEUTICS

  公开号：WO2022187141A1

  公开（公告）日：2022-09-09

  Compounds for activating invariant natural killer T cells (iNKT) cells are provided. Compounds according to certain embodiments activate iNKT cells and induce an increase in the production of one or more cytokines, such as IFNγ, IL-2, IL-4, IL-6 and TNFα. In some embodiments, activated iNKT cells are used to selectively reduce the presence of or eliminate inflammatory senescent cells, such as senescent cells having an inflammatory secretome (SASP). Methods for activating iNKT cells by contacting an iNKT cell with an amount of the subject compounds and selectively reducing the presence of or eliminating senescent cells with activated iNKT cells are also described. Compositions for practicing the subject methods are also described.

  本发明提供了用于激活不变自然杀伤T细胞（iNKT）细胞的化合物。根据某些实施例，这些化合物可以激活iNKT细胞并诱导产生一个或多个细胞因子的增加，例如IFNγ、IL-2、IL-4、IL-6和TNFα。在某些实施例中，激活的iNKT细胞被用于选择性地减少或消除炎症衰老细胞，例如具有炎症分泌物（SASP）的衰老细胞。本发明还描述了通过将iNKT细胞与所述化合物的适量接触来激活iNKT细胞并通过激活的iNKT细胞选择性地减少或消除衰老细胞的方法。还描述了用于实施所述方法的组合物。
• Design, Synthesis, and Functional Activity of Labeled CD1d Glycolipid Agonists
  作者：Peter J. Jervis、Paolo Polzella、Justyna Wojno、John-Paul Jukes、Hemza Ghadbane、Yoel R. Garcia Diaz、Gurdyal S. Besra、Vincenzo Cerundolo、Liam R. Cox

  DOI：10.1021/bc300556e

  日期：2013.4.17

  Invariant natural killer T cells (iNKT cells) are restricted by CD1d molecules and activated upon CD1d-mediated presentation of glycolipids to T cell receptors (TCRs) located on the surface of the cell. Because the cytokine response profile is governed by the structure of the glycolipid, we sought a method for labeling various glycolipids to study their in vivo behavior. The prototypical CD1d agonist, alpha-galactosyl ceramide (alpha-GalCer) 1, instigates a powerful immune response and the generation of a wide range of cytokines when it is presented to iNKT cell TCRs by CD1d molecules. Analysis of crystal structures of the TCR-alpha-GalCer-CD1d ternary complex identified the alpha-methylene unit in the fatty acid side chain, and more specifically the pro-S hydrogen at this position, as a site for incorporating a label. We postulated that modifying the glycolipid in this way would exert a minimal impact on the TCR-glycolipid-CD1d ternary complex, allowing the labeled molecule to function as a good mimic for the CD1d agonist under investigation. To test this hypothesis, the synthesis of a biotinylated version of the CD1d agonist threitol ceramide (ThrCer) was targeted. Both diastereoisomers, epimeric at the label tethering site, were prepared, and functional experiments confirmed the importance of substituting the pro-S, and not the pro-R, hydrogen with the label for optimal activity. Significantly, functional experiments revealed that biotinylated ThrCer (S)-10 displayed behavior comparable to that of ThrCer 5 itself and also confirmed that the biotin residue is available for streptavidin and antibiotin antibody recognition. A second CD1d agonist, namely alpha-GalCer C20:2 4, was modified in a similar way, this time with a fluorescent label. The labeled alpha-GalCer C20:2 analogue (11) again displayed functional behavior comparable to that of its unlabeled substrate, supporting the notion that the alpha-methylene unit in the fatty acid amide chain should be a suitable site for attaching a label to a range of CD1d agonists. The flexibility of the synthetic strategy, and late-stage incorporation of the label, opens up the possibility of using this labeling approach to study the in vivo behavior of a wide range of CD1d agonists.