5-[N-[2-(trimethylsilyl)ethoxycarbonyl]amino]pentan-1-ol | 401601-01-2

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 5-[N-[2-(trimethylsilyl)ethoxycarbonyl]amino]pentan-1-ol
• 英文别名: 5-[N-[2-(trimethylsilyl)ethoxycarbonyl]amino]pentanol；Carbamic acid, (5-hydroxypentyl)-, 2-(trimethylsilyl)ethyl ester；2-trimethylsilylethyl N-(5-hydroxypentyl)carbamate
• CAS: 401601-01-2
• 化学式: C₁₁H₂₅NO₃Si
• 分子量: 247.41
• InChiKey: COFABZCGUKTNEO-UHFFFAOYSA-N

物化性质

• 沸点：
  348.8±27.0 °C(Predicted)
• 密度：
  0.967±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.21
• 重原子数：
  16
• 可旋转键数：
  9
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.91
• 拓扑面积：
  58.6
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5-[N-[2-(trimethylsilyl)ethoxycarbonyl]amino]pentan-1-ol 在 咪唑 、 碘 、 三苯基膦 作用下， 以76%的产率得到5-{N-[2-(trimethylsilyl)ethoxycarbonyl]amino}pentane iodide
  参考文献：
  名称：

  Synthesis of polyamines and polyamine toxins. An improved alkylation procedure

  摘要：

  Polyamines and polyamine toxins are biologically important molecules, having modulatory effects on nucleotides and proteins. Here we present an improved alkylation procedure, which allows sequential synthesis of polyamines and polyamine toxins on solid phase using N-protected aminoalkyl halides and 7-methyl-1,5,7-triazabicyclo[4.4.0]dec-5-ene (MTBD) as base. The feasibility of the procedure is demonstrated with the synthesis of the native polyamine toxin, PhTX-433, as well as an analogue, PhTX-56, which is a very potent and subtype selective glutamate receptor antagonist. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2004.08.139
• 作为产物：
  描述：

  5-氨基-1-戊醇 、 对硝基苯基三甲基硅乙基碳酸酯 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 以87%的产率得到5-[N-[2-(trimethylsilyl)ethoxycarbonyl]amino]pentan-1-ol
  参考文献：
  名称：

  Solid-Phase Synthesis of Polyamine Toxin Analogues:  Potent and Selective Antagonists of Ca²⁺-Permeable AMPA Receptors

  摘要：

  The wasp toxin philanthotoxin-433 (PhTX-433) is a nonselective and noncompetitive antagonist of ionotropic receptors, such as ionotropic glutamate receptors and nicotinic acetylcholine receptors. Polyamine toxins are extensively used for the characterization of subtypes of ionotropic glutamate receptors, in particular Ca2+-permeable AMPA and kainate receptors. We have previously shown that an analogue of PhTX-433 with one of the amino groups replaced by a methylene group, philanthotoxin-83 (PhTX-83) is a selective and potent antagonist of AMPA receptors. We now describe the solid-phase synthesis of analogues of PhTX-83 and the electrophysiological characterization of these analogues on cloned AMPA and kainate receptors. The polyamine portion of PhTX-83 was modified systematically by chaniging the position. of the. secondary amino group along the polyamine chain. In another series of analogues, the acyl moiety of PhTX-83 was replaced by acids of different size and lipophilicity. Using electrophysiological techniques, PhTX-56 was shown to be a highly potent (K-i = 3.3 +/- 0.78 nM) and voltage-dependent antagonist of homomeric GluR1 receptors and was more than 1000-fold less potent when tested on heteromeric GluR1+GluR2, as well as homomeric GluR5(Q) receptors, thus being selective for Ca2+-permeable AMPA receptors. Variation of the acyl group of PhTX-83 had only minor effect on antagonist potency at homomeric GluR receptors but led to a significant decrease in the voltage-dependence. In conclusion, PhTX-56 is a novel, very potent, and selective antagonist of Ca2+-permeable AMPA receptors and is a promising tool for structure/function studies of the ion channel of the AMPA receptor.

  DOI：

  10.1021/jm020314s

文献信息

• Structure–Activity Relationship Studies of Argiotoxins: Selective and Potent Inhibitors of Ionotropic Glutamate Receptors
  作者：Mette H. Poulsen、Simon Lucas、Tinna B. Bach、Anne F. Barslund、Claudius Wenzler、Christel B. Jensen、Anders S. Kristensen、Kristian Strømgaard

  DOI：10.1021/jm301602d

  日期：2013.2.14

  open-channel blocker of ionotropic glutamate (iGlu) receptors. Here, three series of analogues were designed to exploit selectivity among iGlu receptors, taking advantage of a recently developed solid-phase synthetic methodology for the synthesis of ArgTX-636 and analogues. Initially, the importance of secondary amino groups in the polyamine chain was studied by the synthesis of systematically modified

  Argiotoxin-636（ArgTX-636），来自蜘蛛Argiope lobata的天然产物，是离子型谷氨酸（iGlu）受体的有效但非选择性的开放通道阻滞剂。在这里，设计了三个系列的类似物，以利用iGlu受体之间的选择性，利用最近开发的用于合成ArgTX-636和类似物的固相合成方法。最初，通过合成系统修饰的ArgTX-636类似物研究了多胺链中仲氨基的重要性，并对其在NMDA和AMPA受体上的药理活性进行了评估。这导致鉴定出分别优先于NMDA和AMPA受体的两种化合物。通过系统地改变芳族头基和连接基氨基酸，可以进一步修饰这些化合物，从而分别得到对NMDA和AMPA受体具有增强的效力和选择性的化合物。因此，
• Design and synthesis of labeled analogs of PhTX-56, a potent and selective AMPA receptor antagonist
  作者：Trine F. Andersen、Stine B. Vogensen、Lars S. Jensen、Kolja M. Knapp、Kristian Strømgaard

  DOI：10.1016/j.bmc.2005.05.023

  日期：2005.9

  biologically important molecules, having modulatory effects on nucleotides and proteins. The wasp toxin, philanthotoxin-433 (PhTX-433), is a non-selective and uncompetitive antagonist of ionotropic receptors, such as ionotropic glutamate receptors and nicotinic acetylcholine receptors. Polyamine toxins are used for the characterization of subtypes of ionotropic glutamate receptors, the Ca2+-permeable

  多胺和多胺毒素是生物学上重要的分子，对核苷酸和蛋白质具有调节作用。黄蜂毒素philanthotoxin-433（PhTX-433）是离子型受体的非选择性和非竞争性拮抗剂，例如离子型谷氨酸受体和烟碱型乙酰胆碱受体。多胺毒素用于表征离子型谷氨酸受体，可渗透Ca2 +的AMPA和海藻酸酯受体的亚型。天然多胺毒素的衍生物philanthotoxin-56（PhTX-56）最近被证明是Ca2 +渗透性AMPA受体的异常有效和选择性拮抗剂。PhTX-56及其标记的衍生物是用于AMPA受体离子通道结构功能研究的有前途的工具。现在，我们描述3H-，13C-，和15N标记的PhTX-56衍生物用于AMPA受体的分子水平研究。[3H] PhTX-56由具有高比放射性的二碘代前体制备，提供了第一个放射性标记的配体与AMPA受体的成孔部分结合。对于高级生物学NMR研究，使用固相合成法合成了13C和15N标记的Ph
• Uncompetitive Antagonism of AMPA Receptors:  Mechanistic Insights from Studies of Polyamine Toxin Derivatives
  作者：Trine F. Andersen、Denis B. Tikhonov、Ulrik Bølcho、Konstantin Bolshakov、Jared K. Nelson、Florentina Pluteanu、Ian R. Mellor、Jan Egebjerg、Kristian Strømgaard

  DOI：10.1021/jm060606j

  日期：2006.9.1

  Philanthotoxins are uncompetitive antagonists of Ca2+-permeable AMPA receptors presumed to bind to the pore-forming region, but a detailed molecular mechanism for this interaction is missing. Here a small library of novel philanthotoxins was designed and synthesized using a solid-phase strategy. The biological activities were investigated at cloned and "native" AMPA receptors using electrophysiological techniques. A distinct relationship between length of the polyamine moiety and the location of a secondary amino group was observed. Fitting the data to the Woodhull equation allowed the first experimental demonstration of the relative location and orientation of the philanthotoxin molecule in the receptor. These results were corroborated by in silico studies using a homology model of the AMPA receptor ion channel. Together these studies provide strong evidence for a molecular mechanism by which polyamine toxins antagonize the AMPA receptor ion channel and provide the basis for rational development of uncompetitive antagonists of AMPA receptors.
• Solid-Phase Synthesis of Polyamine Toxin Analogues:  Potent and Selective Antagonists of Ca²⁺-Permeable AMPA Receptors
  作者：Hasse Kromann、Sonata Krikstolaityte、Anne J. Andersen、Kim Andersen、Povl Krogsgaard-Larsen、Jerzy W. Jaroszewski、Jan Egebjerg、Kristian Strømgaard

  DOI：10.1021/jm020314s

  日期：2002.12.1

  The wasp toxin philanthotoxin-433 (PhTX-433) is a nonselective and noncompetitive antagonist of ionotropic receptors, such as ionotropic glutamate receptors and nicotinic acetylcholine receptors. Polyamine toxins are extensively used for the characterization of subtypes of ionotropic glutamate receptors, in particular Ca2+-permeable AMPA and kainate receptors. We have previously shown that an analogue of PhTX-433 with one of the amino groups replaced by a methylene group, philanthotoxin-83 (PhTX-83) is a selective and potent antagonist of AMPA receptors. We now describe the solid-phase synthesis of analogues of PhTX-83 and the electrophysiological characterization of these analogues on cloned AMPA and kainate receptors. The polyamine portion of PhTX-83 was modified systematically by chaniging the position. of the. secondary amino group along the polyamine chain. In another series of analogues, the acyl moiety of PhTX-83 was replaced by acids of different size and lipophilicity. Using electrophysiological techniques, PhTX-56 was shown to be a highly potent (K-i = 3.3 +/- 0.78 nM) and voltage-dependent antagonist of homomeric GluR1 receptors and was more than 1000-fold less potent when tested on heteromeric GluR1+GluR2, as well as homomeric GluR5(Q) receptors, thus being selective for Ca2+-permeable AMPA receptors. Variation of the acyl group of PhTX-83 had only minor effect on antagonist potency at homomeric GluR receptors but led to a significant decrease in the voltage-dependence. In conclusion, PhTX-56 is a novel, very potent, and selective antagonist of Ca2+-permeable AMPA receptors and is a promising tool for structure/function studies of the ion channel of the AMPA receptor.
• Synthesis of polyamines and polyamine toxins. An improved alkylation procedure
  作者：Trine Frost Andersen、Kristian Strømgaard

  DOI：10.1016/j.tetlet.2004.08.139

  日期：2004.10

  Polyamines and polyamine toxins are biologically important molecules, having modulatory effects on nucleotides and proteins. Here we present an improved alkylation procedure, which allows sequential synthesis of polyamines and polyamine toxins on solid phase using N-protected aminoalkyl halides and 7-methyl-1,5,7-triazabicyclo[4.4.0]dec-5-ene (MTBD) as base. The feasibility of the procedure is demonstrated with the synthesis of the native polyamine toxin, PhTX-433, as well as an analogue, PhTX-56, which is a very potent and subtype selective glutamate receptor antagonist. (C) 2004 Elsevier Ltd. All rights reserved.