(2S,3S,4R)-2-(N-hexacosanoylamino)-3,4-di-O-benzoyl-1,3,4-octadecanetriol | 209899-68-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (2S,3S,4R)-2-(N-hexacosanoylamino)-3,4-di-O-benzoyl-1,3,4-octadecanetriol
• 英文别名: (2S,3S,4R)-3,4-dibenzoyloxy-2-hexacosanoylamido-octadecan-1-ol；[(2S,3S,4R)-3-benzoyloxy-2-(hexacosanoylamino)-1-hydroxyoctadecan-4-yl] benzoate
• CAS: 209899-68-3
• 化学式: C₅₈H₉₇NO₆
• 分子量: 904.411
• InChiKey: SEHFLRZRIFVVEV-JJEZHPPHSA-N

物化性质

• 沸点：
  910.6±65.0 °C(Predicted)
• 密度：
  0.978±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  22.1
• 重原子数：
  65
• 可旋转键数：
  47
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.74
• 拓扑面积：
  102
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2,3,4,6-tetra-O-acetyl-5-thio-α-D-glactopyranosyl trichloroacetimidate 、 (2S,3S,4R)-2-(N-hexacosanoylamino)-3,4-di-O-benzoyl-1,3,4-octadecanetriol 在 三氟甲磺酸三甲基硅酯 作用下， 以 二氯甲烷 为溶剂， 反应 1.5h， 以35%的产率得到(2S,3S,4R)-2-(N-hexacosanoylamino)-3,4-di-O-benzoyl-1-O-(2,3,4,6-tetra-O-acetyl-5-thio-α-D-galactopyranosyl)-1,3,4-octadecanetriol
  参考文献：
  名称：

  5-Thio-α-GalCers的合成及生物活性

  摘要：

  NKT细胞是识别CD1d分子呈递的糖脂抗原的T细胞的独特子集，被认为可产生Th1和Th2 T细胞的关键细胞因子，因此参与了几种类型的免疫应答的控制。作为具有α-半乳糖基神经酰胺核心结构的活性糖脂抗原，KRN7000显示出有希望的免疫刺激活性，并被选作进一步临床应用的抗癌药物。在本报告中，设计并合成了三个新的KRN7000结构类似物，其中吡喃半乳糖残基的环氧被硫原子以及脂质链上的变异所取代。在体内和体外评估了它们刺激小鼠NKT细胞产生IFN-γ和IL-4的能力。

  DOI：

  10.1021/acsmedchemlett.5b00046
• 作为产物：
  描述：

  糖脂 在 吡啶 、 4-二甲氨基吡啶 、 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 对甲苯磺酸 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 238.0h， 生成 (2S,3S,4R)-2-(N-hexacosanoylamino)-3,4-di-O-benzoyl-1,3,4-octadecanetriol
  参考文献：
  名称：

  An efficient synthesis of a 6″-BODIPY-α-Galactosylceramide probe for monitoring α-Galactosylceramide uptake by cells

  摘要：

  Herein, an efficient synthesis of BODIPY-α-Galactosylceramide 3, which can be used to study the cellular uptake of the potent immunostimulatory parent compound α-Galactosylceramide, is reported. Key in our synthetic strategy is the six-step synthesis of the core BODIPY scaffold (64% yield overall) and its quantitative conversion to an N-hydroxysuccinimidyl ester to facilitate conjugation and purification of the target glycolipid. For the preparation of the core of the glycolipid, the solubility of the lipid acceptor proved to be critical. The ability of BODIPY-αGalCer 3 to activate invariant natural killer cells was then demonstrated in vitro.

  DOI：

  10.1016/j.carres.2019.107840

文献信息

• Synthesis and biological activities of amino acids functionalized α-GalCer analogues
  作者：Weiwei Ma、Jingjing Bi、Chuanfang Zhao、Zhiguo Zhang、Tongxin Liu、Guisheng Zhang

  DOI：10.1016/j.bmc.2019.115141

  日期：2020.1

  T cell receptor with glycolipid antigens presented by CD1d. In this paper, we wish to report a novel series of α-GalCer analogues which were synthesized by incorporation of l-amino acid methyl esters in the C-6' position of glycolipid. The evaluation of these synthetic analogues for their capacities to stimulate iNKT-cells into producing Th1 and Th2 cytokines both in vitro and in vivo indicated that

  不变的自然杀伤性T细胞（iNKT细胞）是操纵免疫系统的有希望的靶标，它们的T细胞受体与CD1d呈递的糖脂抗原结合后，可以迅速释放大量Th1和Th2细胞因子。在本文中，我们希望报道一系列新的α-GalCer类似物，这些类似物是通过在糖脂的C-6'位掺入1-氨基酸甲酯合成的。对这些合成类似物在体外和体内刺激iNKT细胞产生Th1和Th2细胞因子的能力的评估表明，它们是有效的CD1d配体，可以刺激鼠脾细胞释放更高的Th1细胞因子IFN-γ。体外。在体内，Gly-α-GalCer（1）和Lys-α-GalCer（3）表现出比α-GalCer更多的Th1偏向反应，尤其是类似物3在体内与α-GalCer（IFN-γ/ IL-4 = 2.5）相比，对IFN-γ产生的选择性最高（IFN-γ/ IL-4 = 5.32）。这些新颖的α-GalCer类似物可用作有效的X射线晶体探针，以揭示α-GalCer/ C
• Lewis Acid Induced Anomerization of <i>Se</i>-Glycosides. Application to Synthesis of α-<i>Se</i>-GalCer
  作者：Anthony W. McDonagh、Mary F. Mahon、Paul V. Murphy

  DOI：10.1021/acs.orglett.5b03591

  日期：2016.2.5

  galacturonic acid derivatives is reported. The reaction was successful for galacturonic acid when various alkyl, alkenyl, alkynyl, saccharide, steroid, and lipid groups were attached to the anomeric Se atom. An increased amount of TiCl4 and/or higher temperature were needed to ensure completion of the reaction in some cases. Yields were higher for reactions carried out at higher dilution. The reaction was applied

  报道了TiCl 4诱导的半乳糖醛酸衍生物的硒糖苷的异构化。当各种烷基，烯基，炔基，糖，类固醇和脂质基团连接到异头硒原子上时，该反应对于半乳糖醛酸是成功的。在某些情况下，需要增加TiCl 4的量和/或更高的温度以确保反应完成。在较高稀释度下进行的反应的产率较高。该反应用于强力免疫刺激剂α-GalCer（KRN7000）的Se基模拟物的合成。
• Amide-Linked C4″-Saccharide Modification of KRN7000 Provides Potent Stimulation of Human Invariant NKT Cells and Anti-Tumor Immunity in a Humanized Mouse Model
  作者：Noemi Alejandra Saavedra-Avila、Santosh Keshipeddy、Matthew J. Guberman-Pfeffer、Ayax Pérez-Gallegos、Neeraj K. Saini、Carolina Schäfer、Leandro J. Carreño、José A Gascón、Steven A. Porcelli、Amy R. Howell

  DOI：10.1021/acschembio.0c00707

  日期：2020.12.18

  substituent affected the recognition by iNKT cell antigen receptors of the C4″-amide substituted glycolipids in complex with their antigen presenting molecule CD1d. Our findings establish the use of stable C4″-amide linked additions to the sugar moiety for further exploration of the immunological effects of structural modifications of iNKT cell activating glycolipids and highlight the critical need for more

  α-半乳糖苷神经酰胺 (α-GalCers) 激活不变的自然杀伤 T (iNKT) 细胞会刺激强烈的免疫反应和有效的抗肿瘤免疫。已经评估了糖脂结构的许多修饰，以获得这些 T 细胞的活化配体，这些 T 细胞在诱导免疫反应方面具有改变和潜在的有利特性。在这里，我们合成了原型 α-GalCer KRN7000 的变体，在半乳糖环的 C4"-位置上具有酰胺连接的苯基烷烃取代。我们表明，这些变体在小鼠模型中具有较弱的 iNKT 细胞刺激活性，但对人类 iNKT 细胞的活性显着增强。我们研究中最活跃的 C4"-酰胺在 iNKT 细胞反应的部分人源化小鼠模型中显示出强烈的抗肿瘤作用。电脑模拟分析表明，酰胺取代基的系链长度和柔性程度影响了 iNKT 细胞抗原受体对 C4"-酰胺取代糖脂与其抗原呈递分子 CD1d 复合物的识别。我们的研究结果确立了使用稳定的 C4"-酰胺连接添加到糖部分以进一步探索 iNKT
• Structure-Activity Relationship of .alpha.-Galactosylceramides against B16-Bearing Mice
  作者：Masahiro Morita、Kazuhiro Motoki、Kohji Akimoto、Takenori Natori、Teruyuki Sakai、Eiji Sawa、Kazuo Yamaji、Yasuhiko Koezuka、Eiichi Kobayashi、Hideaki Fukushima

  DOI：10.1021/jm00012a018

  日期：1995.6

  Agelasphin-9b, (2S,3S,4R)-1-O-(alpha-D-galactopyranosyl)-16-methyl-2-[N-((R)-2-hydroxytetracosanoyl)-amino]-1,3,4-heptadecanetriol, is a potent antitumor agent isolated from the marine sponge Agelas mauritianus. Various analogues of agelasphin-9b (a lead compound) were synthesized, and the relationship between their structures and biological activities was examined using several assay systems. From the results, KRN7000, (2S,3S;4R)-1-O-(alpha-D-galactopyranosyl)2-(N-hexacosanoylamino)-1,3,4-octadecanetriol, was selected as a candidate for clinical application.
• Synthesis and biological evaluation of α-galactosylceramide (KRN7000) and isoglobotrihexosylceramide (iGb3)
  作者：Chengfeng Xia、Qingjia Yao、Jens Schümann、Emmanuel Rossy、Wenlan Chen、Lizhi Zhu、Wenpeng Zhang、Gennaro De Libero、Peng George Wang

  DOI：10.1016/j.bmcl.2006.01.040

  日期：2006.4

  Glycoceramides call activate NKT cells by binding with CD1d to produce IFN-gamma, IL-4, and other cytokines. An efficient synthetic pathway for alpha-galactosylceramide (KRN7000) was established by coupling a protected galactose donor to a properly protected ceramide. During the investigation, it was discovered that when the ceramide was protected with benzyl groups, only beta-galactosylceramide was produced from the glycosylation reaction. In contrast, the ceramide with benzoyl protecting groups produced alpha-galactosylceramide. Isoglobotrihexosylceramide (iGb3) was prepared by glycosylation of Gal alpha 1-3Gal beta 1-4Glc donor with 2-azidosphingosine in high yield. Biological assays on the synthetic KRN7000 and iGb3 were performed using human and murine iNKT cell clones or hybridomas. (C) 2006 Elsevier Ltd. All rights reserved.