3-(4-benzyloxy-phenyl)-2-butyrylamino-propionic acid methyl ester | 172992-34-6

• 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: 3-(4-benzyloxy-phenyl)-2-butyrylamino-propionic acid methyl ester
• 英文别名: methyl (2S)-2-(butanoylamino)-3-(4-phenylmethoxyphenyl)propanoate
• CAS: 172992-34-6
• 化学式: C₂₁H₂₅NO₄
• 分子量: 355.434
• InChiKey: MZSCIZHQFNGVTB-IBGZPJMESA-N

物化性质

• 沸点：
  541.6±45.0 °C(Predicted)
• 密度：
  1.125±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  26
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  64.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-(4-benzyloxy-phenyl)-2-butyrylamino-propionic acid methyl ester 在 lithium hydroxide 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 乙酸乙酯 为溶剂， 反应 20.0h， 生成 N-butyryl-O-benzyl-L-tyrosine p-nitrophenyl ester
  参考文献：
  名称：

  A Subtype-Selective, Use-Dependent Inhibitor of Native AMPA Receptors

  摘要：

  AMPA (alpha-amino-3-hydroxy-5-methyl-4-isooxazole) receptors (AMPARs) are glutamate-gated ion channels that play central roles in the mammalian brain, mediating fast excitatory synaptic transmission and underlying several forms of synaptic plasticity. Two subtypes of AMPARs are primarily coexpressed at excitatory synapses in adult animals (GluR1/2 and GluR2/3 receptors). Efforts to distinguish between the potentially distinct roles these receptor subtypes play at synapses have been hampered by the absence of a subtype-selective AMPAR antagonist. Here we show that the polyamine philanthotoxin-7,4 (PhTx-74) is a subtype-selective AMPAR antagonist, inhibiting GluR1/2, but not GluR2/3 receptors, use-dependently. The molecular basis for the observed selectivity and a highly efficient synthesis of this remarkable toxin are also presented. PhTx-74 provides the first a means of directly monitoring subtype-specific changes in the composition of AMPARs at native synapses, including during hippocampal long-term potentiation (LTP), a form of synaptic plasticity thought to share processes related to learning and memory.

  DOI：

  10.1021/ja0705801
• 作为产物：
  描述：

  methyl 2S-amino-3-(4-benzyloxyphenyl)propionate hydrochloride 、 丁酰氯 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以83%的产率得到3-(4-benzyloxy-phenyl)-2-butyrylamino-propionic acid methyl ester
  参考文献：
  名称：

  实际合成不对称多胺酰胺

  摘要：

  容易获得的对称多胺的不对称化是合成许多含有多胺的天然产物的重要的第一步。同样，基于某些黄蜂和蜘蛛毒液中存在的通道阻断毒素，在合成多胺酰胺时，多胺酰胺可能可用于基因传递和作为神经保护剂。三氟乙酰基作为保护基的应用使得不对称的多胺酰胺易于以克为单位制备。

  DOI：

  10.1016/s0040-4039(97)10542-1

文献信息

• Practical synthesis of unsymmetrical polyamine amides
  作者：Ian S. Blagbrough、Andrew J. Geall

  DOI：10.1016/s0040-4039(97)10542-1

  日期：1998.1

  polyamine containing natural products. Likewise in the synthesis of polyamine amides which are potentially useful for gene delivery and as neuroprotectants, based upon channel blocking toxins found in certain wasp and spider venoms. The application of trifluoroacetyl as a protecting group allows unsymmetrical polyamine amides to be easily prepared on a gram scale.

  容易获得的对称多胺的不对称化是合成许多含有多胺的天然产物的重要的第一步。同样，基于某些黄蜂和蜘蛛毒液中存在的通道阻断毒素，在合成多胺酰胺时，多胺酰胺可能可用于基因传递和作为神经保护剂。三氟乙酰基作为保护基的应用使得不对称的多胺酰胺易于以克为单位制备。
• Total syntheses of polyamine amides PhTX-4.3.3 and PhTX-3.4.3: Reductive alkylation is a rapid, practical route to philanthotoxins
  作者：Eduardo Moya、Ian S. Blagbrough

  DOI：10.1016/0040-4039(95)01996-u

  日期：1995.12

  Reductive alkylation allows a rapid and practical entry to the polyamine amide wasp toxin philanthotoxin-4.3.3. Philanthotoxin-3.4.3 has been prepared, in two steps, by the monoacylation of spermine. These polyamine amides are selective molecular pharmacological tools for cation channels gated by glutamic acid and acetylcholine, and may have potential as neuroprotective agents.
• A Subtype-Selective, Use-Dependent Inhibitor of Native AMPA Receptors
  作者：Aaron Nilsen、Pamela M. England

  DOI：10.1021/ja0705801

  日期：2007.4.1

  AMPA (alpha-amino-3-hydroxy-5-methyl-4-isooxazole) receptors (AMPARs) are glutamate-gated ion channels that play central roles in the mammalian brain, mediating fast excitatory synaptic transmission and underlying several forms of synaptic plasticity. Two subtypes of AMPARs are primarily coexpressed at excitatory synapses in adult animals (GluR1/2 and GluR2/3 receptors). Efforts to distinguish between the potentially distinct roles these receptor subtypes play at synapses have been hampered by the absence of a subtype-selective AMPAR antagonist. Here we show that the polyamine philanthotoxin-7,4 (PhTx-74) is a subtype-selective AMPAR antagonist, inhibiting GluR1/2, but not GluR2/3 receptors, use-dependently. The molecular basis for the observed selectivity and a highly efficient synthesis of this remarkable toxin are also presented. PhTx-74 provides the first a means of directly monitoring subtype-specific changes in the composition of AMPARs at native synapses, including during hippocampal long-term potentiation (LTP), a form of synaptic plasticity thought to share processes related to learning and memory.