(2S)-dimethyl 2-(3-((S)-4-methoxy-4-oxo-3-(4-(2,2,2-trifluoro-N-methylacetamido)benzamido)butyl)oxiran-2-yl)pentanedioate | 1100130-96-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (2S)-dimethyl 2-(3-((S)-4-methoxy-4-oxo-3-(4-(2,2,2-trifluoro-N-methylacetamido)benzamido)butyl)oxiran-2-yl)pentanedioate
• 英文别名: dimethyl (2S)-2-[3-[(3S)-4-methoxy-3-[[4-[methyl-(2,2,2-trifluoroacetyl)amino]benzoyl]amino]-4-oxobutyl]oxiran-2-yl]pentanedioate
• CAS: 1100130-96-8
• 化学式: C₂₄H₂₉F₃N₂O₉
• 分子量: 546.497
• InChiKey: IHUYNZRPGOTNMM-XNYRCJLNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  38
• 可旋转键数：
  15
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  141
• 氢给体数：
  1
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  (2S)-dimethyl 2-(3-((S)-4-methoxy-4-oxo-3-(4-(2,2,2-trifluoro-N-methylacetamido)benzamido)butyl)oxiran-2-yl)pentanedioate 在 lithium hydroxide monohydrate 作用下， 以 甲醇 为溶剂， 反应 168.0h， 以100%的产率得到(2S)-2-(3-((S)-3-carboxy-3-(4-(methylamino)benzamido)propyl)oxiran-2-yl)pentanedioic acid
  参考文献：
  名称：

  Synthesis of Isopeptide Epoxide Peptidomimetics

  摘要：

  Two epoxide-containing peptidomimetics of the isopeptide, glutatnyl-gamma-glutamate, have been synthesized via a route that should be generally applicable to the synthesis of isopeptide analogues in which an oxirane replaces the scissile peptide bond. Enzymes that catalyze the hydrolysis of peptides and isopeptides are often susceptible to inactivation by electrophilic substrate analogues. In this research, an epoxide was installed as an electrophilic replacement of the scissile isopeptide bond. The C-terminal glutamyl mimic was accessed by the stereospecific synthesis of suitably substituted cyclopentenes, 8 and 10, as surrogates for either the L- or D- enantiomer. The enantiomeric cyclopentenes were further elaborated to incorporate an appended sulfone that was reacted with a suitably protected glutamyl-gamma-semialdehyde in a Julia-Kocienski olefination reaction. This olefination afforded predominantly the desired E-olefin isosteres of L-glutamyl-gamma-D-glutamate and L-glutamyl-gamma-L-glutamate, following which peracid-mediated epoxidation and deprotection provided the epoxide-containing peptidomimetics, 4 and 5.

  DOI：

  10.1021/jo801907p
• 作为产物：
  描述：

  trimethyl (E,3S,8S)-8-[[4-[methyl-(2,2,2-trifluoroacetyl)amino]benzoyl]amino]oct-4-ene-1,3,8-tricarboxylate 在 碳酸氢钠 、 间氯过氧苯甲酸 作用下， 以 二氯甲烷 为溶剂， 反应 24.0h， 以80%的产率得到(2S)-dimethyl 2-(3-((S)-4-methoxy-4-oxo-3-(4-(2,2,2-trifluoro-N-methylacetamido)benzamido)butyl)oxiran-2-yl)pentanedioate
  参考文献：
  名称：

  Synthesis of Isopeptide Epoxide Peptidomimetics

  摘要：

  Two epoxide-containing peptidomimetics of the isopeptide, glutatnyl-gamma-glutamate, have been synthesized via a route that should be generally applicable to the synthesis of isopeptide analogues in which an oxirane replaces the scissile peptide bond. Enzymes that catalyze the hydrolysis of peptides and isopeptides are often susceptible to inactivation by electrophilic substrate analogues. In this research, an epoxide was installed as an electrophilic replacement of the scissile isopeptide bond. The C-terminal glutamyl mimic was accessed by the stereospecific synthesis of suitably substituted cyclopentenes, 8 and 10, as surrogates for either the L- or D- enantiomer. The enantiomeric cyclopentenes were further elaborated to incorporate an appended sulfone that was reacted with a suitably protected glutamyl-gamma-semialdehyde in a Julia-Kocienski olefination reaction. This olefination afforded predominantly the desired E-olefin isosteres of L-glutamyl-gamma-D-glutamate and L-glutamyl-gamma-L-glutamate, following which peracid-mediated epoxidation and deprotection provided the epoxide-containing peptidomimetics, 4 and 5.

  DOI：

  10.1021/jo801907p

文献信息

• Synthesis of Isopeptide Epoxide Peptidomimetics
  作者：Debatosh Majumdar、Matthew D. Alexander、James K. Coward

  DOI：10.1021/jo801907p

  日期：2009.1.16

  Two epoxide-containing peptidomimetics of the isopeptide, glutatnyl-gamma-glutamate, have been synthesized via a route that should be generally applicable to the synthesis of isopeptide analogues in which an oxirane replaces the scissile peptide bond. Enzymes that catalyze the hydrolysis of peptides and isopeptides are often susceptible to inactivation by electrophilic substrate analogues. In this research, an epoxide was installed as an electrophilic replacement of the scissile isopeptide bond. The C-terminal glutamyl mimic was accessed by the stereospecific synthesis of suitably substituted cyclopentenes, 8 and 10, as surrogates for either the L- or D- enantiomer. The enantiomeric cyclopentenes were further elaborated to incorporate an appended sulfone that was reacted with a suitably protected glutamyl-gamma-semialdehyde in a Julia-Kocienski olefination reaction. This olefination afforded predominantly the desired E-olefin isosteres of L-glutamyl-gamma-D-glutamate and L-glutamyl-gamma-L-glutamate, following which peracid-mediated epoxidation and deprotection provided the epoxide-containing peptidomimetics, 4 and 5.