benzyl 2,4,6-tri-O-pivaloyl-β-D-galactopyranosyl-(1->4)-2,3,6-tri-O-pivaloyl-β-D-glucopyranoside | 886034-78-2

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: benzyl 2,4,6-tri-O-pivaloyl-β-D-galactopyranosyl-(1->4)-2,3,6-tri-O-pivaloyl-β-D-glucopyranoside
• 英文别名: pivaloyl(-2)[pivaloyl(-4)][pivaloyl(-6)]Gal(b1-4)[pivaloyl(-2)][pivaloyl(-3)][pivaloyl(-6)]Glc(b)-O-Bn；[(2R,3R,4S,5R,6S)-6-[(2R,3R,4S,5R,6R)-4,5-bis(2,2-dimethylpropanoyloxy)-2-(2,2-dimethylpropanoyloxymethyl)-6-phenylmethoxyoxan-3-yl]oxy-3,5-bis(2,2-dimethylpropanoyloxy)-4-hydroxyoxan-2-yl]methyl 2,2-dimethylpropanoate
• CAS: 886034-78-2
• 化学式: C₄₉H₇₆O₁₇
• 分子量: 937.132
• InChiKey: LWFIIEGMHJKPPG-QTXPGJNTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.6
• 重原子数：
  66
• 可旋转键数：
  25
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.76
• 拓扑面积：
  215
• 氢给体数：
  1
• 氢受体数：
  17

反应信息

• 作为反应物：
  描述：

  benzyl 2,4,6-tri-O-pivaloyl-β-D-galactopyranosyl-(1->4)-2,3,6-tri-O-pivaloyl-β-D-glucopyranoside 、 苯基2,3,4,6-四-O-苯甲基-1-硫代-Β-D-半乳糖皮蒽 在 4 A molecular sieve 、 N-碘代丁二酰亚胺 、 三氟甲磺酸三甲基硅酯 作用下， 以 二氯甲烷 为溶剂， 反应 2.5h， 以84%的产率得到benzyl 2,3,4,6-tetra-O-benzyl-α-D-galactopyranosyl-(1->3)-2,4,6-tri-O-pivaloyl-β-D-galactopyranosyl-(1->4)-2,3,6-tri-O-pivaloyl-β-D-glucopyranoside
  参考文献：
  名称：

  Modification of the Ceramide Moiety of Isoglobotrihexosylceramide on Its Agonist Activity in Stimulation of Invariant Natural Killer T Cells

  摘要：

  Isoglobotrihexosylceramide (iGb3) is an endogenous antigen of mammalian cells and can stimulate invariant natural killer T (iNKT) cells to evoke autoimmune activities by the release of T helper 1 (Th1) and Th2 cytokines. Th1 cytokines are correlated with the antitumor and antiviral response, while Th2 cytokines are correlated with the amelioration of autoimmune diseases. iGb3 is a very weak agonist compared to the exogenous alpha-galactosylceramide; however, modification of the ceramide moiety has been advocated as one of the approaches to improve its stimulatory activity and to change the bias of release of Th1 and Th2 cytokines. Two analogues of iGb3, 2H-iGb3 and HO-iGb3 with different ceramide moieties, were synthesized. Bioassay results showed that HO-iGb3 was much more effective in stimulating iNKT cells than iGb3 at low concentration. The assay also showed that the CD1d/2H-iGb3 complexes are remarkably efficient in stimulating iNKT cells.

  DOI：

  10.1021/jm0701066
• 作为产物：
  描述：

  benzyl 2,4,6-tri-O-pivaloyl-3-(4-methoxybenzyl)-β-D-galactopyranosyl-(1->4)-2,3,6-tri-O-pivaloyl-β-D-glucopyranoside 在 2,3-二氯-5,6-二氰基-1,4-苯醌 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 12.0h， 以76%的产率得到benzyl 2,4,6-tri-O-pivaloyl-β-D-galactopyranosyl-(1->4)-2,3,6-tri-O-pivaloyl-β-D-glucopyranoside
  参考文献：
  名称：

  Modification of the Ceramide Moiety of Isoglobotrihexosylceramide on Its Agonist Activity in Stimulation of Invariant Natural Killer T Cells

  摘要：

  Isoglobotrihexosylceramide (iGb3) is an endogenous antigen of mammalian cells and can stimulate invariant natural killer T (iNKT) cells to evoke autoimmune activities by the release of T helper 1 (Th1) and Th2 cytokines. Th1 cytokines are correlated with the antitumor and antiviral response, while Th2 cytokines are correlated with the amelioration of autoimmune diseases. iGb3 is a very weak agonist compared to the exogenous alpha-galactosylceramide; however, modification of the ceramide moiety has been advocated as one of the approaches to improve its stimulatory activity and to change the bias of release of Th1 and Th2 cytokines. Two analogues of iGb3, 2H-iGb3 and HO-iGb3 with different ceramide moieties, were synthesized. Bioassay results showed that HO-iGb3 was much more effective in stimulating iNKT cells than iGb3 at low concentration. The assay also showed that the CD1d/2H-iGb3 complexes are remarkably efficient in stimulating iNKT cells.

  DOI：

  10.1021/jm0701066

文献信息

• Synthesis and Structure−Activity Relationship Study of Isoglobotrihexosylceramide Analogues
  作者：Wenlan Chen、Chengfeng Xia、Jinhua Wang、Prakash Thapa、Yusen Li、Janos Nadas、Wenpeng Zhang、Dapeng Zhou、Peng George Wang

  DOI：10.1021/jo701539k

  日期：2007.12.1

  killer T (iNKT) cells are innate T lymphocytes that express T cell receptors binding to exogenous and endogenous glycosphingolpid antigens presented by a nonpolymorphic, non-MHC antigen presenting molecule, CD1d. The endogenous glycosphingolipid metabolite, isoglobotrihexosylceramide (iGb3), is the first known natural ligand for both human and mouse iNKT cells, whose activity has been confirmed in a

  不变的自然杀伤性T细胞（iNKT）是先天性T淋巴细胞，表达表达与非多态性，非MHC抗原呈递分子CD1d呈递的外源性和内源性糖鞘脂抗原结合的T细胞受体。内源性鞘糖脂代谢物即异三糖三己糖基神经酰胺（iGb3）是人类和小鼠iNKT细胞的第一个已知天然配体，其活性已在由不同研究人员产生的多种iNKT细胞克隆中得到证实，代表了大部分iNKT细胞群体。T细胞受体介导的信号通路在很大程度上受到糖鞘脂抗原结构变异的影响，从而导致iNKT细胞具有多种多样的生物学功能。为了研究iGb3触发iNKT细胞激活背后的结构要求，iGb3的结构活性关系（SAR）需要进行表征。在这项研究中，合成了包含2'''，3'''，4'''和6'''脱氧末端半乳糖的iGb3类似物，以探测iGb3和TCR之间的SAR。使用鼠iNKT细胞杂交瘤DN32.D3对合成iGb3类似物进行了生物学检测。结果表明，末端半乳糖的2'''和3'''羟
• 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.