benzoic acid 5-(S)-amino-2-(S)-[(1-(S)-carboxy-cyclohexyl-methyl)-carbamoyl]-4-oxo-6-phenyl-hexyl ester trifluroacetate | 1322615-58-6

• 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)-amino-2-(S)-[(1-(S)-carboxy-cyclohexyl-methyl)-carbamoyl]-4-oxo-6-phenyl-hexyl ester trifluroacetate
• 英文别名: (2S)-2-[[(2S,5S)-5-amino-2-(benzoyloxymethyl)-4-oxo-6-phenylhexanoyl]amino]-2-cyclohexylacetic acid;2,2,2-trifluoroacetic acid
• CAS: 1322615-58-6
• 化学式: C₂HF₃O₂*C₂₈H₃₄N₂O₆
• 分子量: 608.612
• InChiKey: NNVLVNPSXXCECF-LTWAPREQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.77
• 重原子数：
  43
• 可旋转键数：
  13
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  173
• 氢给体数：
  4
• 氢受体数：
  12

反应信息

• 作为产物：
  描述：

  benzoic acid 2-(S)-(4-(R)-benzyl-2-oxo-oxazolidine-3-carbonyl)-5-(S)-benzyloxycarbonyl-4-oxo-6-phenyl-hexyl ester 在 lithium hydroxide monohydrate 、 palladium 10% on activated carbon 、 水 、 氢气 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 0.3h， 生成 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

文献信息

• The tandem chain extension aldol reaction used for synthesis of ketomethylene tripeptidomimetics targeting hPEPT1
  作者：Karina Thorn、Carsten Uhd Nielsen、Palle Jakobsen、Bente Steffansen、Charles K. Zercher、Mikael Begtrup

  DOI：10.1016/j.bmcl.2011.05.108

  日期：2011.8

  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.