11-(5-cholesten-3α-yloxy)-3n³₉-trioxaundecan-1-ol | 960624-09-3

• 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: 11-(5-cholesten-3α-yloxy)-3n³₉-trioxaundecan-1-ol
• 英文别名: 5-(cholesten-3-α-yloxy)-3,6,9-trioxaundecanol；2-[2-[2-[2-[[(3R,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]ethanol
• CAS: 960624-09-3
• 化学式: C₃₅H₆₂O₅
• 分子量: 562.874
• InChiKey: VMNHAHOFXOUWGU-SWPLQBLZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8
• 重原子数：
  40
• 可旋转键数：
  17
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.94
• 拓扑面积：
  57.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  11-(5-cholesten-3α-yloxy)-3n³₉-trioxaundecan-1-ol 在 sodium hydride 、 对甲苯磺酸 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 二甲基亚砜 为溶剂， 反应 24.0h， 生成 1-(5-cholesten-3α-yloxy)-20-(methylsulfonyl)oxy-3n³₁₈-hexaoxaicosane
  参考文献：
  名称：

  Synthesis of Cholesterylated Thiogalactosides for Gene Delivery

  摘要：

  A series of cholesterylated thiogalactosides L-1 - L-6 the cell targeting ligands for gene delivery to hepatocytes, was synthesized. Related poly( ethylene glycol) chain was used as a bridge for the attachment of galactoside on one hydroxyl end, while the other hydroxyl end was linked with cholesterol. This design provided an effective entry for the synthesis of a poly( ethylene glycol) compound with the hepatocyte targeting.

  DOI：

  10.1080/00397910600764634
• 作为产物：
  描述：

  胆固醇 在 吡啶 作用下， 以 1,4-二氧六环 为溶剂， 反应 5.0h， 生成 11-(5-cholesten-3α-yloxy)-3n³₉-trioxaundecan-1-ol
  参考文献：
  名称：

  In vitroandin vivoinvestigation of glucose-mediated brain-targeting liposomes

  摘要：

  New glycosyl derivative of cholesterol was synthesized as a material for preparing novel liposome to overcome the ineffective delivery of normal drug formulations to brain by targeting the (glucose transporters) GLUTs on the BBB. Coumarin-6 was used as fluorescent probe. The results have shown that the cytotoxicity for the brain capillary endothelial cells (BCECs) of the glucose-mediated brain targeting liposome containing coumarin-6 was less than that of conventional liposome. The BBB model in vitro was established by coculturing of BCECs and astrocytes (ACs) of rat to test the transendothelial ability crossing the BBB. The transendothelial ability was confirmed strengthen alone with the amount of the new glycosyl derivative of cholesterol used in liposome. After i.v. administration of LIP, control liposome (CLP), and GLP-4, the AUC(0-t) of coumarin-6 for GLP-4 was 2.85 times higher than that of LIP, and 3.33 times higher than that of CLP. The C-max of CLP-4 was 1.43 times higher than that of LIP, and 3.10 times higher than that of CLP. Both pharmacokinetics and distribution in mice were also investigated to show that this novel brain targeting drug delivery system was promising.

  DOI：

  10.3109/10611861003587235

文献信息

• Design, Synthesis and In Vivo Evaluation of Sulfhydryl β-D-Glucose Cholesterols as Ligands for Brain Targeting Liposomes
  作者：Wei Fan、Chengyi Yan、Shan Qian、Nian Yao、Lei Tang、Yong Wu

  DOI：10.2174/157018010790945788

  日期：2010.5.1

  A novel sulfhydryl-β-D-glucose cholesterol 10a-10f as ligand for brain targeting liposomes was designed and synthesized. 10e was applied to the preparation of liposomal delivery system for achieving the brain-targeted delivery of the model drug tegafur in mice utilizing the glucose transporter member 1 (GLUT1). The results suggest the feasibility to enhance liposomes ability of delivering drug to brain by using the designed compound as liposome ligands.

  设计并合成了一种新型硫醇-β-D-葡萄糖胆固醇10a-10f作为脑靶向脂质体的配体。应用10e制备脂质体递送系统，旨在利用葡萄糖转运蛋白成员1（GLUT1）在 mice 中实现模型药物替加氟的脑靶向递送。结果表明，通过使用设计的化合物作为脂质体配体，可以增强脂质体向脑内递送药物的能力。
• Design, synthesis and preliminary bio-evaluation of glucose–cholesterol derivatives as ligands for brain targeting liposomes
  作者：Fan Lei、Wei Fan、Xian Kun Li、Shan Wang、Li Hai、Yong Wu

  DOI：10.1016/j.cclet.2010.12.056

  日期：2011.7

  A series of glucose cholesterol derivatives 8a-8e as ligands for brain targeting liposomes were synthesized. The preparation of compound 6 involved temporary protection of glucose with chlorotrimethylsilicane and hexamethyldisilazane followed by selectively hydrolyzed. The known cholesteryl tosylate 1 were coupled to ethylene glycols to afford alcohol 2a-2e. Substitution and deprotection of alcohol 2a-2e furnished the acids 4a-4e, which was condensed with compound 6 to get compounds 7a-7e, and then was deprotected in tetrahydrofuran with TFA to obtain the title compounds. As a model drug, tegafur was entrapped by liposomes coupled with 8b, and preliminary in vivo evaluation shown 8b could enhance the ability of liposomes delivering tegafur across the blood brain barrier. (C) 2011 Yong Wu. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
• Synthesis of Cholesterylated Thiogalactosides for Gene Delivery
  作者：Li Hai、Jiang Fan、Zhirong Zhang、Guoyao Zhang、Yong Wu

  DOI：10.1080/00397910600764634

  日期：2006.9

  A series of cholesterylated thiogalactosides L-1 - L-6 the cell targeting ligands for gene delivery to hepatocytes, was synthesized. Related poly( ethylene glycol) chain was used as a bridge for the attachment of galactoside on one hydroxyl end, while the other hydroxyl end was linked with cholesterol. This design provided an effective entry for the synthesis of a poly( ethylene glycol) compound with the hepatocyte targeting.
• <i>In vitro</i>and<i>in vivo</i>investigation of glucose-mediated brain-targeting liposomes
  作者：Yao Qin、Wei Fan、Huali Chen、Nian Yao、Wenwei Tang、Jie Tang、Wenmin Yuan、Rui Kuai、Zhirong Zhang、Yong Wu、Qin He

  DOI：10.3109/10611861003587235

  日期：2010.8

  New glycosyl derivative of cholesterol was synthesized as a material for preparing novel liposome to overcome the ineffective delivery of normal drug formulations to brain by targeting the (glucose transporters) GLUTs on the BBB. Coumarin-6 was used as fluorescent probe. The results have shown that the cytotoxicity for the brain capillary endothelial cells (BCECs) of the glucose-mediated brain targeting liposome containing coumarin-6 was less than that of conventional liposome. The BBB model in vitro was established by coculturing of BCECs and astrocytes (ACs) of rat to test the transendothelial ability crossing the BBB. The transendothelial ability was confirmed strengthen alone with the amount of the new glycosyl derivative of cholesterol used in liposome. After i.v. administration of LIP, control liposome (CLP), and GLP-4, the AUC(0-t) of coumarin-6 for GLP-4 was 2.85 times higher than that of LIP, and 3.33 times higher than that of CLP. The C-max of CLP-4 was 1.43 times higher than that of LIP, and 3.10 times higher than that of CLP. Both pharmacokinetics and distribution in mice were also investigated to show that this novel brain targeting drug delivery system was promising.
• Novel synthetic LPDs consisting of different cholesterol derivatives for gene transfer into hepatocytes
  作者：Jiao Lu、Di Zhu、Zhi-Rong Zhang、Li Hai、Yong Wu、Xun Sun

  DOI：10.3109/10611860903548370

  日期：2010.8

  In the present study, LPDs composing of a series of novel synthetic cholesterylated derivatives bearing a cluster of galactose residues and different spacer lengths were prepared for performing target gene delivery to hepatocytes and their physiochemical properties as well as gene transfer efficiency were investigated. In agreement with the "clustering effect" known to occur with more complex oligomeric structures, the addition of galactose residues under optimized spatial arrangement condition invariably increased the transfect efficiency into hepatoma cells, which can be owed to the sufficient binding of galactose ligands to the ASGPR on hepatocytes. However, the gene transfer ability to hepatocytes was not always improved with extended spacer arms, suggesting a spatial binding sites arrangement of the receptor. Moreover, our research has established galactosylated LPDs, specifically, LPDIIb, LPDIIIc, and LPDIVe as potential vectors to deliver special genes into hepatocytes with low toxicity, combining the condensing effect of protamine and the targeting capability of cholesterylated thiogalactosides.