N-(4-methoxybenzyl)-4-methyl-2-oxopentanamide

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: N-(4-methoxybenzyl)-4-methyl-2-oxopentanamide
• 英文别名: N-[(4-methoxyphenyl)methyl]-4-methyl-2-oxopentanamide
• 化学式: C₁₄H₁₉NO₃
• 分子量: 249.31
• InChiKey: HSWDSZATESEZEH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  18
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  55.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-(4-methoxybenzyl)-4-methyl-2-oxopentanamide 在 (2S)-2-[二苯基[(三甲基硅酯)氧基]甲基]-吡咯烷 、 甲醇 、 sodium tetrahydroborate 、 三氟甲磺酸 、 三氟化硼乙醚 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 甲苯 为溶剂， 反应 152.0h， 生成 (1R,4S,5S,6R)-5-isopropyl-2-(4-methoxybenzyl)-1,2,3,4,5,6-hexahydro-1,6-methanobenzo[c]azocin-4-ol
  参考文献：
  名称：

  通过有机催化和超强酸活化合成对映体富集的亚甲基桥连苯并恶唑。

  摘要：

  以直接的方式实现与生物活性天然产物有关的对映体富集的精细三维分子的合成仍然是有机合成中的长期追求。对映选择性有机催化潜在地提供了解决这一问题的独特机会，特别是当与互补的活化方式结合使用时。在这里，我们报告简单线性非手性容易获得的前体的有机催化和超强酸活化的顺序关联，以促进表现出三到五个完全受控的立体中心的独特的高度精细的手性亚甲基桥联的苯并氮烷的形成。这种奇特的骨架很难通过标准的合成方法组装，与具有生物活性的天然和合成吗啡喃和苯并吗啡紧密相关。

  DOI：

  10.1002/anie.201912043
• 作为产物：
  描述：

  (S)-methyl 2-((2-(hydroxyamino)-2-oxoethyl)(4-methoxybenzyl)amino)-4-methylpentanoate 在 4-二甲氨基吡啶 、 N,N-二异丙基乙胺 、 2,3-二氯-5,6-二氰基-1,4-苯醌 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 六甲基磷酰三胺 、 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 7.0h， 生成 N-(4-methoxybenzyl)-4-methyl-2-oxopentanamide
  参考文献：
  名称：

  Synthesis of Natural Flutimide and Analogous Fully Substituted Pyrazine-2,6-diones, Endonuclease Inhibitors of Influenza Virus

  摘要：

  Flutimide, a fully substituted 1-hydroxy-3H-pyrazine-2,6-dione, is a fungal metabolite isolated from a new species of Delitschia. cofertaspora. It has been shown to selectively inhibit cap-dependent endonuclease activity of influenza virus A. The inhibition of this activity is a target for the potential development of a therapeutic agent to treat influenza infections. A convergent total synthesis of flutimide starting from L-leucine has been described. The synthetic methodology has been extended to include the synthesis of specifically designed aromatic analogues of flutimide, some of which exhibited greater than 7-fold improvement in activity, The most potent compounds were those with p-fluorobenzylidene or p-methoxybenzylidene substitutions at C-5 of 3H-pyrazine-2,6-dione and showed IC50 values of 0.9 and 0.8 muM, respectively. The details of the rationale for the synthetic design, syntheses, and biological activities of these analogues are described.

  DOI：

  10.1021/jo015665d

文献信息

• Enantioenriched Methylene‐Bridged Benzazocanes Synthesis by Organocatalytic and Superacid Activations
  作者：Rodolphe Beaud、Bastien Michelet、Yasmin Reviriot、Agnès Martin‐Mingot、Jean Rodriguez、Damien Bonne、Sébastien Thibaudeau

  DOI：10.1002/anie.201912043

  日期：2020.1.13

  bioactive natural products remains a long-standing quest in organic synthesis. Enantioselective organocatalysis potentially offers a unique opportunity to solve this problem, especially when combined with complementary modes of activation. Here, we report the sequential association of organocatalytic and superacid activations of simple linear achiral readily available precursors to promote the formation

  以直接的方式实现与生物活性天然产物有关的对映体富集的精细三维分子的合成仍然是有机合成中的长期追求。对映选择性有机催化潜在地提供了解决这一问题的独特机会，特别是当与互补的活化方式结合使用时。在这里，我们报告简单线性非手性容易获得的前体的有机催化和超强酸活化的顺序关联，以促进表现出三到五个完全受控的立体中心的独特的高度精细的手性亚甲基桥联的苯并氮烷的形成。这种奇特的骨架很难通过标准的合成方法组装，与具有生物活性的天然和合成吗啡喃和苯并吗啡紧密相关。
• Synthesis of Natural Flutimide and Analogous Fully Substituted Pyrazine-2,6-diones, Endonuclease Inhibitors of Influenza Virus
  作者：Sheo B. Singh、Joanne E. Tomassini

  DOI：10.1021/jo015665d

  日期：2001.8.1

  Flutimide, a fully substituted 1-hydroxy-3H-pyrazine-2,6-dione, is a fungal metabolite isolated from a new species of Delitschia. cofertaspora. It has been shown to selectively inhibit cap-dependent endonuclease activity of influenza virus A. The inhibition of this activity is a target for the potential development of a therapeutic agent to treat influenza infections. A convergent total synthesis of flutimide starting from L-leucine has been described. The synthetic methodology has been extended to include the synthesis of specifically designed aromatic analogues of flutimide, some of which exhibited greater than 7-fold improvement in activity, The most potent compounds were those with p-fluorobenzylidene or p-methoxybenzylidene substitutions at C-5 of 3H-pyrazine-2,6-dione and showed IC50 values of 0.9 and 0.8 muM, respectively. The details of the rationale for the synthetic design, syntheses, and biological activities of these analogues are described.