3-oleoylamidolithocholic acid | 799271-35-5

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 英文名称: 3-oleoylamidolithocholic acid
• CAS: 799271-35-5
• 化学式: C₄₂H₇₃NO₃
• 分子量: 640.047
• InChiKey: VIPHDFJJYZNYES-UKVFTGQJSA-N

物化性质

• 沸点：
  745.2±39.0 °C(Predicted)
• 密度：
  1.01±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  11.67
• 重原子数：
  46.0
• 可旋转键数：
  20.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.9
• 拓扑面积：
  66.4
• 氢给体数：
  2.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  3-oleoylamidolithocholic acid 、 O-tert-butyl-N-tyrosinylglycinyltris{(1-[2-(2-aminoethoxy)ethoxy]ethoxy-2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-β-D-galactosamine)(carboxyethoxymethyl)}methane 在 1-羟基苯并三唑 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以80%的产率得到3-oleoylamidolithocholic acid [O-tert-butyl-N-tyrosinylglycinyltris{(1-[2-(2-aminoethoxy)ethoxy]ethoxy-2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-β-D-galactosamine)(carboxyethoxymethyl)}methane]
  参考文献：
  名称：

  Design and Synthesis of Novel N-Acetylgalactosamine-Terminated Glycolipids for Targeting of Lipoproteins to the Hepatic Asialoglycoprotein Receptor

  摘要：

  A novel glycolipid has been prepared that contains a cluster glycoside with an unusually high affinity for the asialoglycoprotein receptor (ASGPr) and a bile acid moiety that mediates stable incorporation into lipidic particles. The glycolipid spontaneously associated with low-density lipoproteins (LDL) and high-density lipoproteins (HDL) within human and murine plasma, and loading of lipoproteins with this glycolipid resulted in an efficient dose-dependent recognition and uptake of LDL and HDL by the liver (and not by spleen) upon intravenous injection into wild-type mice. Preinjection with asialoorosomucoid largely inhibited the uptake, establishing that both HDL and LDL were selectively recognized and processed by the ASGPr on liver parenchymal cells. Finally, repeated intravenous administration of the glycolipid to hyperlipidemic LDL receptor-deficient mice evoked an efficient and persistent cholesterol-lowering effect. These results indicate that the glycolipid may be a promising alternative for the treatment of hyperlipidemic patients who do not respond sufficiently to current cholesterol-lowering therapies.

  DOI：

  10.1021/jm049481d
• 作为产物：
  描述：

  异石胆酸 在 吡啶 、 1,3-丙二硫醇 、 盐酸 、 sodium hydroxide 、 sodium azide 、 三乙胺 作用下， 以 1,4-二氧六环 、 甲醇 、 1,2-二氯乙烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 54.5h， 生成 3-oleoylamidolithocholic acid
  参考文献：
  名称：

  Design and Synthesis of Novel N-Acetylgalactosamine-Terminated Glycolipids for Targeting of Lipoproteins to the Hepatic Asialoglycoprotein Receptor

  摘要：

  A novel glycolipid has been prepared that contains a cluster glycoside with an unusually high affinity for the asialoglycoprotein receptor (ASGPr) and a bile acid moiety that mediates stable incorporation into lipidic particles. The glycolipid spontaneously associated with low-density lipoproteins (LDL) and high-density lipoproteins (HDL) within human and murine plasma, and loading of lipoproteins with this glycolipid resulted in an efficient dose-dependent recognition and uptake of LDL and HDL by the liver (and not by spleen) upon intravenous injection into wild-type mice. Preinjection with asialoorosomucoid largely inhibited the uptake, establishing that both HDL and LDL were selectively recognized and processed by the ASGPr on liver parenchymal cells. Finally, repeated intravenous administration of the glycolipid to hyperlipidemic LDL receptor-deficient mice evoked an efficient and persistent cholesterol-lowering effect. These results indicate that the glycolipid may be a promising alternative for the treatment of hyperlipidemic patients who do not respond sufficiently to current cholesterol-lowering therapies.

  DOI：

  10.1021/jm049481d