(2S)-2-((2S)-2-((3R)-3-(benzylamino)-3-((3aR,6S,6aR)-6-(benzyloxy)-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-5-yl)propanamido)-3-methylbutanamido)propanoic acid

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 英文名称: (2S)-2-((2S)-2-((3R)-3-(benzylamino)-3-((3aR,6S,6aR)-6-(benzyloxy)-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-5-yl)propanamido)-3-methylbutanamido)propanoic acid
• 英文别名: (2S)-2-[[(2S)-2-[[(3R)-3-[(3aR,6S,6aR)-6-benzyloxy-2,2-dimethyl-3a,5,6,6a-tetrahydrofuro[2,3-d][1,3]dioxol-5-yl]-3-(benzylamino)propanoyl]amino]-3-methyl-butanoyl]amino]propanoic acid；(2S)-2-[[(2S)-2-[[(3R)-3-[(3aR,6S,6aR)-2,2-dimethyl-6-phenylmethoxy-3a,5,6,6a-tetrahydrofuro[2,3-d][1,3]dioxol-5-yl]-3-(benzylamino)propanoyl]amino]-3-methylbutanoyl]amino]propanoic acid
• 化学式: C₃₂H₄₃N₃O₈
• 分子量: 597.709
• InChiKey: DGEFXLGHKUINMX-DOHLPABLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  43
• 可旋转键数：
  14
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  144
• 氢给体数：
  4
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  (2S)-2-((2S)-2-((3R)-3-(benzylamino)-3-((3aR,6S,6aR)-6-(benzyloxy)-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-5-yl)propanamido)-3-methylbutanamido)propanoic acid 在 palladium 10% on activated carbon 、 环己烯 作用下， 以 乙醇 为溶剂， 反应 2.5h， 以44%的产率得到(2S)-2-((2S)-2-((3R)-3-amino-3-((3aR,6S,6aR)-6-hydroxy-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-5-yl)propanamido)-3-methylbutanamido)propanoic acid
  参考文献：
  名称：

  Synthesis and molecular modelling studies of novel carbapeptide analogs for inhibition of HIV-1 protease

  摘要：

  Novel glycopeptides containing amino acids such as valine and alanine were designed, synthesized and tested for inhibition of the wild type C-SA HIV-1 protease enzyme. The incorporation of dipeptide sequences Val-Ala/Ala-Val to the sugar B-amino acid at two side chain positions resulted in a series of nine novel compounds. Compounds 3a, 3b, 3c, 3d, 4a, 4b and 5 displayed significant activities against the HIV protease enzyme. The glycopeptides are orders of magnitude less toxic to human MT-4 cells than lopinavir. Computational results were in good agreement with the experimental HIV-PR activity. The sugar hydroxyl group at the C-3 position interacts with the enzymatic Asp25/Asp25' residues. The docked position of the inhibitor is preserved during MD simulations and at least five hydrogen bond forms between the inhibitor and the enzymatic pocket. The results provide a platform for the progress of more effective carbohydrate supported inhibitors of HIV-1 and other aspartic proteases. (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.03.027
• 作为产物：
  描述：

  在 水 、 N,N-二异丙基乙胺 、 lithium hydroxide 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 2.5h， 生成 (2S)-2-((2S)-2-((3R)-3-(benzylamino)-3-((3aR,6S,6aR)-6-(benzyloxy)-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-5-yl)propanamido)-3-methylbutanamido)propanoic acid
  参考文献：
  名称：

  Synthesis and molecular modelling studies of novel carbapeptide analogs for inhibition of HIV-1 protease

  摘要：

  Novel glycopeptides containing amino acids such as valine and alanine were designed, synthesized and tested for inhibition of the wild type C-SA HIV-1 protease enzyme. The incorporation of dipeptide sequences Val-Ala/Ala-Val to the sugar B-amino acid at two side chain positions resulted in a series of nine novel compounds. Compounds 3a, 3b, 3c, 3d, 4a, 4b and 5 displayed significant activities against the HIV protease enzyme. The glycopeptides are orders of magnitude less toxic to human MT-4 cells than lopinavir. Computational results were in good agreement with the experimental HIV-PR activity. The sugar hydroxyl group at the C-3 position interacts with the enzymatic Asp25/Asp25' residues. The docked position of the inhibitor is preserved during MD simulations and at least five hydrogen bond forms between the inhibitor and the enzymatic pocket. The results provide a platform for the progress of more effective carbohydrate supported inhibitors of HIV-1 and other aspartic proteases. (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.03.027

文献信息

• Synthesis and molecular modelling studies of novel carbapeptide analogs for inhibition of HIV-1 protease
  作者：Sachin A. Pawar、Amit M. Jabgunde、Patrick Govender、Glenn E.M. Maguire、Hendrik G. Kruger、Raveen Parboosing、Mahmoud E.S. Soliman、Yasien Sayed、Dilip D. Dhavale、Thavendran Govender

  DOI：10.1016/j.ejmech.2012.03.027

  日期：2012.7

  Novel glycopeptides containing amino acids such as valine and alanine were designed, synthesized and tested for inhibition of the wild type C-SA HIV-1 protease enzyme. The incorporation of dipeptide sequences Val-Ala/Ala-Val to the sugar B-amino acid at two side chain positions resulted in a series of nine novel compounds. Compounds 3a, 3b, 3c, 3d, 4a, 4b and 5 displayed significant activities against the HIV protease enzyme. The glycopeptides are orders of magnitude less toxic to human MT-4 cells than lopinavir. Computational results were in good agreement with the experimental HIV-PR activity. The sugar hydroxyl group at the C-3 position interacts with the enzymatic Asp25/Asp25' residues. The docked position of the inhibitor is preserved during MD simulations and at least five hydrogen bond forms between the inhibitor and the enzymatic pocket. The results provide a platform for the progress of more effective carbohydrate supported inhibitors of HIV-1 and other aspartic proteases. (C) 2012 Elsevier Masson SAS. All rights reserved.