(2S,3S,4R)-2-(N-hexacosanoylamino)-3,4-di-O-benzoyl-1-O-(triphenylmethyl)-1,3,4-octadecanetriol | 209899-67-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: (2S,3S,4R)-2-(N-hexacosanoylamino)-3,4-di-O-benzoyl-1-O-(triphenylmethyl)-1,3,4-octadecanetriol
• 英文别名: (2S,3S,4R)-3,4-dibenzoyloxy-2-hexacosanoylamido-1-triphenylmethyoxy-octadecane；[(2S,3S,4R)-3-benzoyloxy-2-(hexacosanoylamino)-1-trityloxyoctadecan-4-yl] benzoate
• CAS: 209899-67-2
• 化学式: C₇₇H₁₁₁NO₆
• 分子量: 1146.73
• InChiKey: XSXXUABXJQGJHU-ZSLBICHMSA-N

物化性质

• 沸点：
  1055.3±65.0 °C(Predicted)
• 密度：
  1.008±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  27.3
• 重原子数：
  84
• 可旋转键数：
  52
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  90.9
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (2S,3S,4R)-2-(N-hexacosanoylamino)-3,4-di-O-benzoyl-1-O-(triphenylmethyl)-1,3,4-octadecanetriol 在 对甲苯磺酸 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 12.0h， 以88%的产率得到(2S,3S,4R)-2-(N-hexacosanoylamino)-3,4-di-O-benzoyl-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 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 212.0h， 生成 (2S,3S,4R)-2-(N-hexacosanoylamino)-3,4-di-O-benzoyl-1-O-(triphenylmethyl)-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

• 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.
• Synthesis and Biological Activities of 5-Thio-α-GalCers
  作者：Jingjing Bi、Jing Wang、Kai Zhou、Yuancheng Wang、Min Fang、Yuguo Du

  DOI：10.1021/acsmedchemlett.5b00046

  日期：2015.4.9

  the control of several types of immune response. As an active glycolipid antigen having α-galactosyl ceramide core structure, KRN7000 showed promising immunostimulation activity and was selected as an anticancer drug candidate for further clinical application. In this report, three new KRN7000 structural analogues were designed and synthesized, in which the ring oxygen of the galactopyranose residue

  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。
• An efficient synthesis of a 6″-BODIPY-α-Galactosylceramide probe for monitoring α-Galactosylceramide uptake by cells
  作者：Janice M.H. Cheng、Stephanie H. Chee、Yusuf Dölen、Martijn Verdoes、Mattie S.M. Timmer、Bridget L. Stocker

  DOI：10.1016/j.carres.2019.107840

  日期：2019.12

  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.