cholest-5-en-3β-yl N,N-bis(2-hydroxyethyl)carbamate | 141287-73-2

• 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: cholest-5-en-3β-yl N,N-bis(2-hydroxyethyl)carbamate
• 英文别名: 3β-(diethanolamine-carbamoyl)cholesterol；N-cholesteryl diethanolamine；[(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] N,N-bis(2-hydroxyethyl)carbamate
• CAS: 141287-73-2
• 化学式: C₃₂H₅₅NO₄
• 分子量: 517.793
• InChiKey: JTQFNXBYNKVTFD-PTHRTHQKSA-N

物化性质

• 熔点：
  159-161 °C(Solv: chloroform (67-66-3); methanol (67-56-1))
• 沸点：
  616.9±55.0 °C(Predicted)
• 密度：
  1.08±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  7.8
• 重原子数：
  37
• 可旋转键数：
  11
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.91
• 拓扑面积：
  70
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  cholest-5-en-3β-yl N,N-bis(2-hydroxyethyl)carbamate 在 periodic acid dihydrate 、 间氯过氧苯甲酸 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 2.0h， 生成 5α,6β-dihydroxycholestan-3β-yl N,N-bis(2-hydroxyethyl)carbamate
  参考文献：
  名称：

  Structure–activity relationship studies of Niemann-Pick type C1-like 1 (NPC1L1) ligands identified by screening assay monitoring pharmacological chaperone effect

  摘要：

  A number of hereditary diseases are caused by defective protein trafficking due to a folding defect resulting from point mutations in proteins. Ligands that bind to the folding intermediates of such mutant proteins and rescue their trafficking defects, known as pharmacological chaperones, have promise for the treatment of certain genetic diseases, including Fabry disease, cystic fibrosis, and Niemann-Pick disease type C. Here we show that this pharmacological chaperone effect can be used for ligand screening, that is, binding of candidate ligands can be detected by monitoring the ligand-mediated correction of a localization defect caused by artificially introduced point mutations of the protein of interest. Using this method, we discovered novel steroidal ligands of Niemann-Pick type C1-like 1 (NPC1L1), an intestinal cholesterol transporter that is the target of the cholesterol absorption inhibitor ezetimibe, and conducted structure-activity relationship studies. We also present data indicating that the binding site of the new ligands is distinct from both the N-terminal sterol-binding domain and the ezetimibe-binding site. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.06.022
• 作为产物：
  描述：

  胆固醇 在 三乙胺 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 生成 cholest-5-en-3β-yl N,N-bis(2-hydroxyethyl)carbamate
  参考文献：
  名称：

  Structure-Activity Relationships of Cytotoxic Cholesterol-Modified DNA Duplexes

  摘要：

  Short DNA duplexes with cholesterol linked at the 3'-terminus of each strand have unique, selective cytotoxic properties. The structural requirements for biological activity were explored through chemical synthesis of analogs and testing in cultured hepatoma cells. Effects of modifications to the sequence, backbone, 3'-sterol, 3'-linker, and 5'-terminus were evaluated. Self-complementary 3'-modified oligodeoxynucleotide (ODN) 10-mers were prepared from solid supports bearing the modification and linker of interest. Any changes to the normal phosphodiester backbone were poorly tolerated. The presence of cholesterol or a closely related sterol was an absolute requirement for activity. The length and position of attachment of the linker to cholesterol was important, with longer linkers showing reduced activity. Large, lipophilic groups at the 5'-terminus gave reduced cytotoxicity and poor solubility properties. The short length and unique structure of these ODNs allowed efficient automated synthesis on a 400 mu mol scale and simplified purification.

  DOI：

  10.1021/jm00022a025

文献信息

• New cationic lipids for gene transfer with high efficiency and low toxicity: T-shape cholesterol ester derivatives
  作者：Yan Lee、Heebeom Koo、Yong-beom Lim、Youngeun Lee、Heejung Mo、Jong Sang Park

  DOI：10.1016/j.bmcl.2004.02.061

  日期：2004.5

  New degradable cationic ester lipids with 'T-shape' configurations were synthesized and tested for gene delivery carrier. Their transfection efficiency and toxicity were compared with commercially available cationic lipids, DOTMA, DOSPA, and DC-Chol. They showed efficient transfection activity and almost no toxicity on mammalian cell lines. Their ester bond degradation was monitored by H-1 NMR. (C) 2004 Elsevier Ltd. All rights reserved.
• Oligo(FcDC-<i>co</i>-CholDEA) with Ferrocene in the Main Chain and Cholesterol as a Pendant Group—Preparation and Unusual Properties
  作者：Junlin Yan、Jing Liu、Yuanhui Sun、Ping Jing、Panli He、Di Gao、Yu Fang

  DOI：10.1021/jp1032838

  日期：2010.10.21

  With ever-increasing need for thin, flexible, and functional materials in electrochemical systems, various techniques have been explored for creating materials used in fuel cells, batteries, electrochromic devices, solar cells, and sensors. In the present study, a novel ferrocene (Fc) and cholesterol (Chol)-containing oligomer, oligo(FcDC-co-CholDEA), was specially designed and prepared by putting Fc in the main chain and Chol as a side group. MALDI-TOF MS and freezing point depression measurements revealed that in average each oligomer contains three Fc units and three Chol units. Cyclic voltammetric measurements revealed that the oligomer displays superior electrochemical stability if compared with other Fc derivatives containing only one Fc unit and one or two Chol unit and with poly(ferrocenylsilane) with Fc in the main chain. In particular, the Fc-containing oligomer possesses an unusual oxidation center, of which the oxidation potential could be as high as 1.81 V. The oligomer is also superior in self-assembly, as demonstrated by forming an LB film of layered structures. Furthermore, supramolecular films with high mechanical strength in the wet state can be prepared by employing a simple solution casting method. This finding demonstrates that self-assembly is a simple but effective. way to create films of potential uses in real-life applications provided proper building blocks are designed and employed.
• Structure–activity relationship studies of Niemann-Pick type C1-like 1 (NPC1L1) ligands identified by screening assay monitoring pharmacological chaperone effect
  作者：Fumika Karaki、Kenji Ohgane、Kosuke Dodo、Yuichi Hashimoto

  DOI：10.1016/j.bmc.2013.06.022

  日期：2013.9

  A number of hereditary diseases are caused by defective protein trafficking due to a folding defect resulting from point mutations in proteins. Ligands that bind to the folding intermediates of such mutant proteins and rescue their trafficking defects, known as pharmacological chaperones, have promise for the treatment of certain genetic diseases, including Fabry disease, cystic fibrosis, and Niemann-Pick disease type C. Here we show that this pharmacological chaperone effect can be used for ligand screening, that is, binding of candidate ligands can be detected by monitoring the ligand-mediated correction of a localization defect caused by artificially introduced point mutations of the protein of interest. Using this method, we discovered novel steroidal ligands of Niemann-Pick type C1-like 1 (NPC1L1), an intestinal cholesterol transporter that is the target of the cholesterol absorption inhibitor ezetimibe, and conducted structure-activity relationship studies. We also present data indicating that the binding site of the new ligands is distinct from both the N-terminal sterol-binding domain and the ezetimibe-binding site. (C) 2013 Elsevier Ltd. All rights reserved.
• Structure-Activity Relationships of Cytotoxic Cholesterol-Modified DNA Duplexes
  作者：Michael W. Reed、Eugeny Lukhtanov、Vladimir Gorn、Deborah D. Lucas、James H. Zhou、S. Balakrishna Pai、Yung-chi Cheng、Rich B. Meyer

  DOI：10.1021/jm00022a025

  日期：1995.10

  Short DNA duplexes with cholesterol linked at the 3'-terminus of each strand have unique, selective cytotoxic properties. The structural requirements for biological activity were explored through chemical synthesis of analogs and testing in cultured hepatoma cells. Effects of modifications to the sequence, backbone, 3'-sterol, 3'-linker, and 5'-terminus were evaluated. Self-complementary 3'-modified oligodeoxynucleotide (ODN) 10-mers were prepared from solid supports bearing the modification and linker of interest. Any changes to the normal phosphodiester backbone were poorly tolerated. The presence of cholesterol or a closely related sterol was an absolute requirement for activity. The length and position of attachment of the linker to cholesterol was important, with longer linkers showing reduced activity. Large, lipophilic groups at the 5'-terminus gave reduced cytotoxicity and poor solubility properties. The short length and unique structure of these ODNs allowed efficient automated synthesis on a 400 mu mol scale and simplified purification.