benzoic acid 5-(S)-benzyloxycarbonylamino-2-(S)-[(1-(S)-tert-butoxycarbonyl-cyclohexyl-methyl)-carbamoyl]-4-oxo-6-phenyl-hexyl ester | 1322615-77-9

• 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: benzoic acid 5-(S)-benzyloxycarbonylamino-2-(S)-[(1-(S)-tert-butoxycarbonyl-cyclohexyl-methyl)-carbamoyl]-4-oxo-6-phenyl-hexyl ester
• CAS: 1322615-77-9
• 化学式: C₄₀H₄₈N₂O₈
• 分子量: 684.83
• InChiKey: XRVWXOHWWUUJHB-BVPJJHLOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.36
• 重原子数：
  50.0
• 可旋转键数：
  15.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  137.1
• 氢给体数：
  2.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  benzoic acid 5-(S)-benzyloxycarbonylamino-2-(S)-[(1-(S)-tert-butoxycarbonyl-cyclohexyl-methyl)-carbamoyl]-4-oxo-6-phenyl-hexyl ester 、 三氟乙酸 在 palladium 10% on activated carbon 、 氢气 作用下， 以 甲醇 为溶剂， 以63%的产率得到benzoic acid 5-(S)-amino-2-(S)-[(1-(S)-carboxy-cyclohexyl-methyl)-carbamoyl]-4-oxo-6-phenyl-hexyl ester trifluroacetate
  参考文献：
  名称：

  The tandem chain extension aldol reaction used for synthesis of ketomethylene tripeptidomimetics targeting hPEPT1

  摘要：

  The rationale for targeting the human di-/tripeptide transporter hPEPT1 for oral drug delivery has been well established by several drug and prodrug cases. The aim of this study was to synthesize novel ketomethylene modified tripeptidomimetics and to investigate their binding affinity for hPEPT1. Three related tripeptidomimetics of the structure H-Phe-psi[COCH2]-Ser(Bz)-X-aa-OH were synthesized applying the tandem chain extension aldol reaction, where amino acid derived beta-keto imides were stereoselectively converted to alpha-substituted gamma-keto imides. In addition, three corresponding tripeptides, composed of amide bonds, were synthesized for comparison of binding affinities. The six investigated compounds were all defined as high affinity ligands (K-i-values < 0.5 mM) for hPEPT1 by measuring the concentration dependent inhibition of apical [C-14]Gly-Sar uptake in Caco-2 cells. Consequently, the ketomethylene replacement for the natural amide bond and alpha-side chain modifications appears to offer a promising strategy to modify tripeptidic structures while maintaining a high affinity for hPEPT1. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.05.108
• 作为产物：
  描述：

  benzoic acid 2-(S)-(4-(R)-benzyl-2-oxo-oxazolidine-3-carbonyl)-5-(S)-[benzyloxycarbonyl-(4-methoxy-benzyl)-amino]-4-oxo-6-phenyl-hexyl ester 在 ammonium cerium (IV) nitrate 、 lithium hydroxide monohydrate 、 水 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 0.88h， 生成 benzoic acid 5-(S)-benzyloxycarbonylamino-2-(S)-[(1-(S)-tert-butoxycarbonyl-cyclohexyl-methyl)-carbamoyl]-4-oxo-6-phenyl-hexyl ester
  参考文献：
  名称：

  The tandem chain extension aldol reaction used for synthesis of ketomethylene tripeptidomimetics targeting hPEPT1

  摘要：

  The rationale for targeting the human di-/tripeptide transporter hPEPT1 for oral drug delivery has been well established by several drug and prodrug cases. The aim of this study was to synthesize novel ketomethylene modified tripeptidomimetics and to investigate their binding affinity for hPEPT1. Three related tripeptidomimetics of the structure H-Phe-psi[COCH2]-Ser(Bz)-X-aa-OH were synthesized applying the tandem chain extension aldol reaction, where amino acid derived beta-keto imides were stereoselectively converted to alpha-substituted gamma-keto imides. In addition, three corresponding tripeptides, composed of amide bonds, were synthesized for comparison of binding affinities. The six investigated compounds were all defined as high affinity ligands (K-i-values < 0.5 mM) for hPEPT1 by measuring the concentration dependent inhibition of apical [C-14]Gly-Sar uptake in Caco-2 cells. Consequently, the ketomethylene replacement for the natural amide bond and alpha-side chain modifications appears to offer a promising strategy to modify tripeptidic structures while maintaining a high affinity for hPEPT1. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.05.108