tert-butyl (2R)-5-hydroxy-2-[(2-methylpropan-2-yl)oxycarbonyl-phenylmethoxycarbonylamino]pentanoate | 125049-98-1

• 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: tert-butyl (2R)-5-hydroxy-2-[(2-methylpropan-2-yl)oxycarbonyl-phenylmethoxycarbonylamino]pentanoate
• CAS: 125049-98-1
• 化学式: C₂₂H₃₃NO₇
• 分子量: 423.507
• InChiKey: SAXZLAINBCKIAF-QGZVFWFLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  30
• 可旋转键数：
  12
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  102
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  tert-butyl (2R)-5-hydroxy-2-[(2-methylpropan-2-yl)oxycarbonyl-phenylmethoxycarbonylamino]pentanoate 在 戴斯-马丁氧化剂 作用下， 以 二氯甲烷 为溶剂， 生成 tert-butyl (2R)-2-[(2-methylpropan-2-yl)oxycarbonyl-phenylmethoxycarbonylamino]-5-oxopentanoate
  参考文献：
  名称：

  Ureido-Based Peptidomimetic Inhibitors of Herpes Simplex Virus Ribonucleotide Reductase:  An Investigation of Inhibitor Bioactive Conformation

  摘要：

  We have been investigating peptidomimetic inhibitors of herpes simplex virus (HSV) ribonucleotide reductase (RR). These inhibitors bind to the HSV RR large subunit and consequently prevent subunit association and subsequent enzymatic activity. This report introduces a new series of compounds that contain an extra nitrogen (a ureido function) at the inhibitor N-terminus. This nitrogen improves inhibitor binding potency 50-fold over our first published inhibitor series. Evidence supports that this improvement in potency results from a new hydrogen-bonding contact between the inhibitor and the RR large subunit. This report also provides evidence for the bioactive conformation around two important amino acid residues contained in our inhibitors. A tert-butyl group, which contributes 100-fold to inhibitor potency but does not directly bind to the large subunit, favors an extended beta-strand conformation that is prevalent in solution and in the bound state. More significantly, the bioactive conformation around a pyrrolidine-modified asparagine residue, which contributes over 30 000-fold to inhibitor potency, is elucidated through a series of conformationally restricted analogues.

  DOI：

  10.1021/jm950825x
• 作为产物：
  描述：

  Cbz-D-N(Boc)Glu(Oallyl)-OtBu 在 四氢吡咯 、 N-甲基吗啉 、 sodium tetrahydroborate 、 四(三苯基膦)钯 、 氯甲酸乙酯 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 生成 tert-butyl (2R)-5-hydroxy-2-[(2-methylpropan-2-yl)oxycarbonyl-phenylmethoxycarbonylamino]pentanoate
  参考文献：
  名称：

  Ureido-Based Peptidomimetic Inhibitors of Herpes Simplex Virus Ribonucleotide Reductase:  An Investigation of Inhibitor Bioactive Conformation

  摘要：

  We have been investigating peptidomimetic inhibitors of herpes simplex virus (HSV) ribonucleotide reductase (RR). These inhibitors bind to the HSV RR large subunit and consequently prevent subunit association and subsequent enzymatic activity. This report introduces a new series of compounds that contain an extra nitrogen (a ureido function) at the inhibitor N-terminus. This nitrogen improves inhibitor binding potency 50-fold over our first published inhibitor series. Evidence supports that this improvement in potency results from a new hydrogen-bonding contact between the inhibitor and the RR large subunit. This report also provides evidence for the bioactive conformation around two important amino acid residues contained in our inhibitors. A tert-butyl group, which contributes 100-fold to inhibitor potency but does not directly bind to the large subunit, favors an extended beta-strand conformation that is prevalent in solution and in the bound state. More significantly, the bioactive conformation around a pyrrolidine-modified asparagine residue, which contributes over 30 000-fold to inhibitor potency, is elucidated through a series of conformationally restricted analogues.

  DOI：

  10.1021/jm950825x

文献信息

• Ureido-Based Peptidomimetic Inhibitors of Herpes Simplex Virus Ribonucleotide Reductase:  An Investigation of Inhibitor Bioactive Conformation
  作者：Neil Moss、Pierre Beaulieu、Jean-Simon Duceppe、Jean-Marie Ferland、Jean Gauthier、Elise Ghiro、Sylvie Goulet、Ingrid Guse、Montse Llinàs-Brunet、Raymond Plante、Louis Plamondon、Dominik Wernic、Robert Déziel

  DOI：10.1021/jm950825x

  日期：1996.1.1

  We have been investigating peptidomimetic inhibitors of herpes simplex virus (HSV) ribonucleotide reductase (RR). These inhibitors bind to the HSV RR large subunit and consequently prevent subunit association and subsequent enzymatic activity. This report introduces a new series of compounds that contain an extra nitrogen (a ureido function) at the inhibitor N-terminus. This nitrogen improves inhibitor binding potency 50-fold over our first published inhibitor series. Evidence supports that this improvement in potency results from a new hydrogen-bonding contact between the inhibitor and the RR large subunit. This report also provides evidence for the bioactive conformation around two important amino acid residues contained in our inhibitors. A tert-butyl group, which contributes 100-fold to inhibitor potency but does not directly bind to the large subunit, favors an extended beta-strand conformation that is prevalent in solution and in the bound state. More significantly, the bioactive conformation around a pyrrolidine-modified asparagine residue, which contributes over 30 000-fold to inhibitor potency, is elucidated through a series of conformationally restricted analogues.