2,3,4,6-tetra-O-acetyl-α-D-galactopyranosyl-(1->3)-2,4,6-tri-O-pivaloyl-β-D-galactopyranosyl-(1->4)-2,3,6-tri-O-pivaloyl-β-D-glucopyranosyl-(1->1)-(2S,3R,4E)-2-hexacosanoylamino-3-O-(4-methoxybenzyl)-4-octadecen-1,3-diol | 886034-83-9

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 鞘脂
• 英文名称: 2,3,4,6-tetra-O-acetyl-α-D-galactopyranosyl-(1->3)-2,4,6-tri-O-pivaloyl-β-D-galactopyranosyl-(1->4)-2,3,6-tri-O-pivaloyl-β-D-glucopyranosyl-(1->1)-(2S,3R,4E)-2-hexacosanoylamino-3-O-(4-methoxybenzyl)-4-octadecen-1,3-diol
• 英文别名: [(2R,3R,4S,5R,6R)-3-[(2S,3R,4S,5S,6R)-3,5-bis(2,2-dimethylpropanoyloxy)-6-(2,2-dimethylpropanoyloxymethyl)-4-[(2R,3R,4S,5S,6R)-3,4,5-triacetyloxy-6-(acetyloxymethyl)oxan-2-yl]oxyoxan-2-yl]oxy-4,5-bis(2,2-dimethylpropanoyloxy)-6-[(E,2S,3R)-2-(hexacosanoylamino)-3-[(4-methoxyphenyl)methoxy]octadec-4-enoxy]oxan-2-yl]methyl 2,2-dimethylpropanoate
• CAS: 886034-83-9
• 化学式: C₁₀₈H₁₈₁NO₂₉
• 分子量: 1957.61
• InChiKey: ZUDIGTULCSMODC-JPHJINGOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  28
• 重原子数：
  138
• 可旋转键数：
  79
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  366
• 氢给体数：
  1
• 氢受体数：
  29

反应信息

• 作为反应物：
  描述：

  2,3,4,6-tetra-O-acetyl-α-D-galactopyranosyl-(1->3)-2,4,6-tri-O-pivaloyl-β-D-galactopyranosyl-(1->4)-2,3,6-tri-O-pivaloyl-β-D-glucopyranosyl-(1->1)-(2S,3R,4E)-2-hexacosanoylamino-3-O-(4-methoxybenzyl)-4-octadecen-1,3-diol 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 以87%的产率得到
  参考文献：
  名称：

  Synthesis and biological evaluation of α-galactosylceramide (KRN7000) and isoglobotrihexosylceramide (iGb3)

  摘要：

  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.

  DOI：

  10.1016/j.bmcl.2006.01.040
• 作为产物：
  描述：

  、 蜡酸 在 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 以 四氢呋喃 为溶剂， 生成 2,3,4,6-tetra-O-acetyl-α-D-galactopyranosyl-(1->3)-2,4,6-tri-O-pivaloyl-β-D-galactopyranosyl-(1->4)-2,3,6-tri-O-pivaloyl-β-D-glucopyranosyl-(1->1)-(2S,3R,4E)-2-hexacosanoylamino-3-O-(4-methoxybenzyl)-4-octadecen-1,3-diol
  参考文献：
  名称：

  Synthesis and biological evaluation of α-galactosylceramide (KRN7000) and isoglobotrihexosylceramide (iGb3)

  摘要：

  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.

  DOI：

  10.1016/j.bmcl.2006.01.040

文献信息

• Modification of the Ceramide Moiety of Isoglobotrihexosylceramide on Its Agonist Activity in Stimulation of Invariant Natural Killer T Cells
  作者：Chengfeng Xia、Jens Schümann、Rossy Emmanuel、Yalong Zhang、Wenlan Chen、Wenpeng Zhang、Gennaro De Libero、Peng George Wang

  DOI：10.1021/jm0701066

  日期：2007.7.1

  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.