N^α-{(S)-α-methoxy-α-(trifluoromethyl)phenylacetoyl}-L-His-(Nim-Tr)-L-Ile-L-Val-L-Pro-NH₂

• 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: N^α-{(S)-α-methoxy-α-(trifluoromethyl)phenylacetoyl}-L-His-(Nim-Tr)-L-Ile-L-Val-L-Pro-NH₂
• 英文别名: (2S)-1-[(2S)-3-methyl-2-[[(2S,3S)-3-methyl-2-[[(2S)-2-[[(2S)-3,3,3-trifluoro-2-methoxy-2-phenylpropanoyl]amino]-3-(3-tritylimidazol-4-yl)propanoyl]amino]pentanoyl]amino]butanoyl]pyrrolidine-2-carboxamide
• 化学式: C₅₁H₅₈F₃N₇O₆
• 分子量: 922.06
• InChiKey: CAULKUVSHYYVMO-VPYSCELYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.7
• 重原子数：
  67
• 可旋转键数：
  19
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  178
• 氢给体数：
  4
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  N^α-{(S)-α-methoxy-α-(trifluoromethyl)phenylacetoyl}-L-His-(Nim-Tr)-L-Ile-L-Val-L-Pro-NH₂ 在 三异丙基硅烷 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 以70%的产率得到N^α-{(S)-α-methoxy-α-(trifluoromethyl)phenylacetoyl}-L-His-LIle-L-Val-L-Pro-NH₂
  参考文献：
  名称：

  Diverted total synthesis of falcitidin acyl tetrapeptides as new antimalarial leads

  摘要：

  We report not only the convergent total synthesis of falcitidin, a natural inhibitor of falcipain-2 from myxobacterium Chitinophaga, but also its diversification into a new antimalarial class of N-acyl tetrapeptides (Acyl-His-Ile-Val-Pro-NH2). Despite the lack of whole-cell activity of falcitidin itself, our study led to the identification of a trifluoromethyl (CF3) analogue displaying sub-micromolar IC50 activity against Plasmodium falciparum 3D7 in a standard blood-cell assay, but only when N-tritylated on its histidine (imidazole) residue. (c) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2014.02.008
• 作为产物：
  描述：

  L-脯氨酰胺 在 哌啶 、 4-二甲氨基吡啶 、 1-羟基苯并三唑 、 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 二氯甲烷 为溶剂， 生成 N^α-{(S)-α-methoxy-α-(trifluoromethyl)phenylacetoyl}-L-His-(Nim-Tr)-L-Ile-L-Val-L-Pro-NH₂
  参考文献：
  名称：

  Diverted total synthesis of falcitidin acyl tetrapeptides as new antimalarial leads

  摘要：

  We report not only the convergent total synthesis of falcitidin, a natural inhibitor of falcipain-2 from myxobacterium Chitinophaga, but also its diversification into a new antimalarial class of N-acyl tetrapeptides (Acyl-His-Ile-Val-Pro-NH2). Despite the lack of whole-cell activity of falcitidin itself, our study led to the identification of a trifluoromethyl (CF3) analogue displaying sub-micromolar IC50 activity against Plasmodium falciparum 3D7 in a standard blood-cell assay, but only when N-tritylated on its histidine (imidazole) residue. (c) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2014.02.008

文献信息

• Diverted total synthesis of falcitidin acyl tetrapeptides as new antimalarial leads
  作者：Santosh R. Kotturi、Brinda Somanadhan、Jun-Hong Ch’ng、Kevin S.-W. Tan、Mark S. Butler、Martin J. Lear

  DOI：10.1016/j.tetlet.2014.02.008

  日期：2014.3

  We report not only the convergent total synthesis of falcitidin, a natural inhibitor of falcipain-2 from myxobacterium Chitinophaga, but also its diversification into a new antimalarial class of N-acyl tetrapeptides (Acyl-His-Ile-Val-Pro-NH2). Despite the lack of whole-cell activity of falcitidin itself, our study led to the identification of a trifluoromethyl (CF3) analogue displaying sub-micromolar IC50 activity against Plasmodium falciparum 3D7 in a standard blood-cell assay, but only when N-tritylated on its histidine (imidazole) residue. (c) 2014 Elsevier Ltd. All rights reserved.