H-L-Asu(OBzl)-Aib-L-Phe-D-Pro-OH TFA salt | 291312-78-2

• 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: H-L-Asu(OBzl)-Aib-L-Phe-D-Pro-OH TFA salt
• CAS: 291312-78-2
• 化学式: C₂HF₃O₂*C₃₃H₄₄N₄O₇
• 分子量: 722.759
• InChiKey: TYLMZRAVZPBQDH-XOOUMMMVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.34
• 重原子数：
  51.0
• 可旋转键数：
  16.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.49
• 拓扑面积：
  205.43
• 氢给体数：
  5.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  H-L-Asu(OBzl)-Aib-L-Phe-D-Pro-OH TFA salt 在 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以72%的产率得到(-)-benzyl 6-[(3S,9S,14aR)-9-benzyl-6,6-dimethyl-1,4,7,10-tetraoxotetradecahydropyrrolo[1,2-a][1,4,7,10]tetraazacyclododecin-3-yl]hexanoate
  参考文献：
  名称：

  Evaluation of functional groups on amino acids in cyclic tetrapeptides in histone deacetylase inhibition

  摘要：

  The naturally occurring cyclic tetrapeptide, chlamydocin, originally isolated from fungus , consists of alpha-aminoisobutyric acid, -phenylalanine, -proline and an unusual amino acid ()-2-amino-8-(()-oxiran-2-yl)-8-oxooctanoic acid (Aoe) and inhibits the histone deacetylases (HDACs), a class of regulatory enzymes. The epoxyketone moiety of Aoe is the key functional group for inhibition. The cyclic tetrapeptide scaffold is supposed to play important role for effective binding to the surface of enzymes. In place of the epoxyketone group, hydroxamic acid and sulfhydryl group have been applied to design inhibitor ligands to zinc atom in catalytic site of HDACs. In the research for more potent HDAC inhibitors, we replaced the epoxyketone moiety of Aoe with different functional groups and synthesized a series of chlamydocin analogs as HDAC inhibitors. Among the functional groups, methoxymethylketone moiety showed as potent inhibition as the hydroxamic acid. On the contrary, we confirmed that borate, trifruoromethylketone, and 2-aminoanilide are almost inactive in HDAC inhibition.

  DOI：

  10.1007/s00726-011-0947-6
• 作为产物：
  描述：

  H-L-Phe-D-Pro-OtBu 在 palladium on activated charcoal 、 氢气 、 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 作用下， 以 溶剂黄146 、 N,N-二甲基甲酰胺 为溶剂， 反应 39.0h， 生成 H-L-Asu(OBzl)-Aib-L-Phe-D-Pro-OH TFA salt
  参考文献：
  名称：

  Evaluation of functional groups on amino acids in cyclic tetrapeptides in histone deacetylase inhibition

  摘要：

  The naturally occurring cyclic tetrapeptide, chlamydocin, originally isolated from fungus , consists of alpha-aminoisobutyric acid, -phenylalanine, -proline and an unusual amino acid ()-2-amino-8-(()-oxiran-2-yl)-8-oxooctanoic acid (Aoe) and inhibits the histone deacetylases (HDACs), a class of regulatory enzymes. The epoxyketone moiety of Aoe is the key functional group for inhibition. The cyclic tetrapeptide scaffold is supposed to play important role for effective binding to the surface of enzymes. In place of the epoxyketone group, hydroxamic acid and sulfhydryl group have been applied to design inhibitor ligands to zinc atom in catalytic site of HDACs. In the research for more potent HDAC inhibitors, we replaced the epoxyketone moiety of Aoe with different functional groups and synthesized a series of chlamydocin analogs as HDAC inhibitors. Among the functional groups, methoxymethylketone moiety showed as potent inhibition as the hydroxamic acid. On the contrary, we confirmed that borate, trifruoromethylketone, and 2-aminoanilide are almost inactive in HDAC inhibition.

  DOI：

  10.1007/s00726-011-0947-6