<(1-thio-β-D-galactopyranosyl)oxy>ethyl 11-(5-cholesten-3β-yloxy)-3,6,9-trioxaundecanyl phosphorothioate | 132156-15-1

• 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: <(1-thio-β-D-galactopyranosyl)oxy>ethyl 11-(5-cholesten-3β-yloxy)-3,6,9-trioxaundecanyl phosphorothioate
• 英文别名: 2-[2-[2-[2-[[(3S,8S,9S,10R,13R,14S,17R)-10,13-dimethyl-17-[(2R)-6-methylheptan-2-yl]-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-yl]oxy]ethoxy]ethoxy]ethoxy]ethoxy-hydroxy-sulfido-[2-[(2S,3R,4S,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]sulfanylethoxy]phosphanium
• CAS: 132156-15-1；132203-34-0
• 化学式: C₄₃H₇₇O₁₂PS₂
• 分子量: 881.183
• InChiKey: KBWODSBZTZPKNC-UQIYZELNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7
• 重原子数：
  58
• 可旋转键数：
  25
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.95
• 拓扑面积：
  192
• 氢给体数：
  5
• 氢受体数：
  14

反应信息

• 作为产物：
  描述：

  2-hydroxyethyl 2',3',4',6'-tetra-O-acetyl-1'-thio-β-D-galactopyranoside 在 ammonium hydroxide 、 syn-2-pyridinealdoxime 、 1,1,2,3-四甲基胍 作用下， 以 1,4-二氧六环 、 吡啶 、 甲醇 为溶剂， 反应 12.25h， 生成 <(1-thio-β-D-galactopyranosyl)oxy>ethyl 11-(5-cholesten-3β-yloxy)-3,6,9-trioxaundecanyl phosphorothioate
  参考文献：
  名称：

  Water-soluble cholesteryl-containing phosphorothioate monogalactosides: synthesis, properties, and use in lowering blood cholesterol by directing plasma lipoproteins to the liver

  摘要：

  The synthesis of several monogalactoside-terminated phosphorothiolated cholesteryl derivatives is described. Monogalactosyl derivatives are coupled by phosphorothiolation to cholesterol by using ethylene glycol units as hydrophilic spacer moieties. The resulting compounds are easily soluble in water. Upon addition of such solutions to human serum (to 2 mM final concentration) the compounds are readily incorporated into lipoproteins. Isolated low-density lipoprotein (LDL) and high-density lipoprotein (HDL), preloaded with the compounds, are rapidly cleared from the circulation by the liver. The hepatic association is blocked by N-acetylgalactosamine, which indicates that galactose-specific recognition sites are responsible for the increased liver uptake. The plasma clearance and hepatic uptake of LDL loaded with the compounds is substantially higher (about 2-fold) than clearance and uptake of HDL containing the compounds. The selectivity of the effects of monogalactoside-terminated phosphorothiolated cholesteryl derivatives on the in vivo behavior of LDL as compared to that of HDL indicates that these compounds might be used to lower specifically LDL levels in patients with a high LDL-cholesterol level.

  DOI：

  10.1021/jm00107a024

文献信息

• Water-soluble cholesteryl-containing phosphorothioate monogalactosides: synthesis, properties, and use in lowering blood cholesterol by directing plasma lipoproteins to the liver
  作者：Harlof C. P. F. Roelen、Martin K. Bijsterbosch、Hille F. Bakkeren、Theo J. C. Van Berkel、Herman J. M. Kempen、Marinus Buytenhek、Gijs A. Van der Marel、Jacques H. Van Boom

  DOI：10.1021/jm00107a024

  日期：1991.3

  The synthesis of several monogalactoside-terminated phosphorothiolated cholesteryl derivatives is described. Monogalactosyl derivatives are coupled by phosphorothiolation to cholesterol by using ethylene glycol units as hydrophilic spacer moieties. The resulting compounds are easily soluble in water. Upon addition of such solutions to human serum (to 2 mM final concentration) the compounds are readily incorporated into lipoproteins. Isolated low-density lipoprotein (LDL) and high-density lipoprotein (HDL), preloaded with the compounds, are rapidly cleared from the circulation by the liver. The hepatic association is blocked by N-acetylgalactosamine, which indicates that galactose-specific recognition sites are responsible for the increased liver uptake. The plasma clearance and hepatic uptake of LDL loaded with the compounds is substantially higher (about 2-fold) than clearance and uptake of HDL containing the compounds. The selectivity of the effects of monogalactoside-terminated phosphorothiolated cholesteryl derivatives on the in vivo behavior of LDL as compared to that of HDL indicates that these compounds might be used to lower specifically LDL levels in patients with a high LDL-cholesterol level.