(4R,5S)-1-tert-butoxycarbonyl-5-(tert-butyldimethylsilyloxymethyl)-4-(4-(phenylsulfonyloxy)but-1-en-2-yl)pyrrolidin-2-one | 874454-33-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (4R,5S)-1-tert-butoxycarbonyl-5-(tert-butyldimethylsilyloxymethyl)-4-(4-(phenylsulfonyloxy)but-1-en-2-yl)pyrrolidin-2-one
• 英文别名: tert-butyl (2S,3R)-3-[4-(benzenesulfonyloxy)but-1-en-2-yl]-2-[[tert-butyl(dimethyl)silyl]oxymethyl]-5-oxopyrrolidine-1-carboxylate
• CAS: 874454-33-8
• 化学式: C₂₆H₄₁NO₇SSi
• 分子量: 539.766
• InChiKey: HCHJINFTBGSZIN-FGZHOGPDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.51
• 重原子数：
  36
• 可旋转键数：
  12
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  108
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (4R,5S)-1-tert-butoxycarbonyl-5-(tert-butyldimethylsilyloxymethyl)-4-(4-(phenylsulfonyloxy)but-1-en-2-yl)pyrrolidin-2-one 在 RhCl(PPh₃)3 、 lithium hexamethyldisilazane 、 儿萘酚硼烷 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 22.0h， 生成 (1R,4S,5R,6RS)-N-tert-butoxycarbonyl-3-aza-4-(tert-butyldimethylsilyloxymethyl)-6-(hydroxymethyl)bicyclo[3.3.0]octane
  参考文献：
  名称：

  Rational Design and Enantioselective Synthesis of (1R,4S,5R,6S)-3-Azabicyclo[3.3.0]octane-4,6-dicarboxylic Acid A Novel Inhibitor at Human Glutamate Transporter Subtypes 1, 2, and 3

  摘要：

  The natural product kainic acid is used as template for the rational design of a novel conformationally restricted (S)-glutamic acid (Glu) analogue, (1R,4S,5R,6S)-3-azabicyclo[3.3.0]octane-4,6-dicarboxylic acid (1a). The target structure 1a was synthesized from commercially available (S)-pyroglutaminol, in an enantioselective fashion, in 14 steps. Pharmacological characterization of 1a at human glutamate transporter subtypes 1, 2, and 3 yielded K-i values of 127, 52, and 46 mu M, respectively. Furthermore, binding studies at native ionotropic Glu (iGlu) receptors revealed low affinity for (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)-preferring, iGlu receptors (IC50 > 100 mu M), whereas affinities for the KAIN-preferring iGlu receptors and the N-methyl-D-aspartate (NMDA)-preferrin- group of iGlu receptors were in the low micromolar range (IC50 = 14 and 2.9 mu M, respectively). At metabotropic Glu receptors (mGluR), EC50 values for 1a were > 1000 mu M for mGluR1 and 4, representing group I and III, respectively, and similar to 1000 mu M (agonist) for mGluR2, representing group II.

  DOI：

  10.1021/jm0508336
• 作为产物：
  描述：

  (4R,5S)-1-tert-butoxycarbonyl-5-(tert-butyldimethylsilyloxymethyl)-4-(4-(4-methoxybenzyloxy)but-1-en-2-yl)pyrrolidin-2-one 在 4-二甲氨基吡啶 、 三乙胺 、 2,3-二氯-5,6-二氰基-1,4-苯醌 作用下， 以 二氯甲烷 为溶剂， 反应 5.0h， 生成 (4R,5S)-1-tert-butoxycarbonyl-5-(tert-butyldimethylsilyloxymethyl)-4-(4-(phenylsulfonyloxy)but-1-en-2-yl)pyrrolidin-2-one
  参考文献：
  名称：

  Rational Design and Enantioselective Synthesis of (1R,4S,5R,6S)-3-Azabicyclo[3.3.0]octane-4,6-dicarboxylic Acid A Novel Inhibitor at Human Glutamate Transporter Subtypes 1, 2, and 3

  摘要：

  The natural product kainic acid is used as template for the rational design of a novel conformationally restricted (S)-glutamic acid (Glu) analogue, (1R,4S,5R,6S)-3-azabicyclo[3.3.0]octane-4,6-dicarboxylic acid (1a). The target structure 1a was synthesized from commercially available (S)-pyroglutaminol, in an enantioselective fashion, in 14 steps. Pharmacological characterization of 1a at human glutamate transporter subtypes 1, 2, and 3 yielded K-i values of 127, 52, and 46 mu M, respectively. Furthermore, binding studies at native ionotropic Glu (iGlu) receptors revealed low affinity for (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)-preferring, iGlu receptors (IC50 > 100 mu M), whereas affinities for the KAIN-preferring iGlu receptors and the N-methyl-D-aspartate (NMDA)-preferrin- group of iGlu receptors were in the low micromolar range (IC50 = 14 and 2.9 mu M, respectively). At metabotropic Glu receptors (mGluR), EC50 values for 1a were > 1000 mu M for mGluR1 and 4, representing group I and III, respectively, and similar to 1000 mu M (agonist) for mGluR2, representing group II.

  DOI：

  10.1021/jm0508336

文献信息

• Rational Design and Enantioselective Synthesis of (1<i>R</i>,4<i>S</i>,5<i>R</i>,6<i>S</i>)-3-Azabicyclo[3.3.0]octane-4,6-dicarboxylic Acid A Novel Inhibitor at Human Glutamate Transporter Subtypes 1, 2, and 3
  作者：Lennart Bunch、Birgitte Nielsen、Anders A. Jensen、Hans Bräuner-Osborne

  DOI：10.1021/jm0508336

  日期：2006.1.1

  The natural product kainic acid is used as template for the rational design of a novel conformationally restricted (S)-glutamic acid (Glu) analogue, (1R,4S,5R,6S)-3-azabicyclo[3.3.0]octane-4,6-dicarboxylic acid (1a). The target structure 1a was synthesized from commercially available (S)-pyroglutaminol, in an enantioselective fashion, in 14 steps. Pharmacological characterization of 1a at human glutamate transporter subtypes 1, 2, and 3 yielded K-i values of 127, 52, and 46 mu M, respectively. Furthermore, binding studies at native ionotropic Glu (iGlu) receptors revealed low affinity for (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)-preferring, iGlu receptors (IC50 > 100 mu M), whereas affinities for the KAIN-preferring iGlu receptors and the N-methyl-D-aspartate (NMDA)-preferrin- group of iGlu receptors were in the low micromolar range (IC50 = 14 and 2.9 mu M, respectively). At metabotropic Glu receptors (mGluR), EC50 values for 1a were > 1000 mu M for mGluR1 and 4, representing group I and III, respectively, and similar to 1000 mu M (agonist) for mGluR2, representing group II.