Boc-Gly-Sar-MeLeu-OH | 133499-00-0

• 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: Boc-Gly-Sar-MeLeu-OH
• 英文别名: Boc-Gly-sarcosyl-ψ(CONCH3)Leu-OH；Boc-Gly-Sar-N(Me)Leu-OH；(2S)-4-methyl-2-[methyl-[2-[methyl-[2-[(2-methylpropan-2-yl)oxycarbonylamino]acetyl]amino]acetyl]amino]pentanoic acid
• CAS: 133499-00-0
• 化学式: C₁₇H₃₁N₃O₆
• 分子量: 373.45
• InChiKey: DULYBEDWZHKLHX-LBPRGKRZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  26
• 可旋转键数：
  10
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.76
• 拓扑面积：
  116
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  Boc-Gly-Sar-MeLeu-OH 以22%的产率得到
  参考文献：
  名称：

  SEEBACH, DIETER;BOSSLER, HANS;GRUNDLER, HANSJORG;SHODA, SHIN-ICHIRO;WENGE+, HELV. CHIM. ACTA, 74,(1991) N, C. 197-224

  摘要：

  DOI：
• 作为产物：
  描述：

  t-BuOCO-Gly-Sar-OH 在 palladium on activated charcoal 氢气 、 双(2-氧代-3-恶唑烷基)次磷酰氯 、 N,N-二异丙基乙胺 作用下， 以 乙醇 为溶剂， 反应 16.5h， 生成 Boc-Gly-Sar-MeLeu-OH
  参考文献：
  名称：

  通过含有肌氨酸锂醇单元的多官能化和LiCl溶剂化的衍生物的C烷基化

  摘要：

  三肽和六肽衍生物Boc-Gly-Sar-MeLeu-OH（5b），Boc-Ala-Sar-Sar-OH（6b），Boc-Ala-Sar-MeLeu-OH（7b）和Boc-Abu-Sar -OH -MeLeu-Val-MeLeu-Ala-OH（12b）可以被多去质子化（分别为三硫代和五硫代衍生物K和P），并因此在肌氨酸（Sar）部分上用MeI和烯丙基或PhCH 2 Br进行C-烷基化。将多晶化的物质溶解在THF中，并通过添加过量的碱（二异丙基氨基锂（LDA）），添加的LiCl和/或助溶剂N，N来改变其反应活性。′-二甲基丙烯脲（DMPU）。优化7b（表3）和12b（方案8）情况下的甲基化反应条件，得到的产物中，离析物的Sar残基已转化为Me-D-Ala单元，产率为80（9c / 8c）和67％（14c / 13c），非对映选择性约为ca。4：1。三肽5b和6b仅包含一个立体生成中心，观察到选

  DOI：

  10.1002/hlca.19910740121

文献信息

• In vitro evaluation of N-methyl amide tripeptidomimetics as substrates for the human intestinal di-/tri-peptide transporter hPEPT1
  作者：Rikke Andersen、Carsten Uhd Nielsen、Mikael Begtrup、Flemming Steen Jørgensen、Birger Brodin、Sven Frokjaer、Bente Steffansen

  DOI：10.1016/j.ejps.2006.03.007

  日期：2006.7

  oral absorption of tripeptides is generally mediated by the human intestinal di-/tri-peptide transporter, hPEPT1. However, the bioavailability of tripeptides is often limited due to degradation in the GI-tract by various peptidases. The aim of the present study was to evaluate the general application of N-methyl amide bioisosteres as peptide bond replacements in tripeptides in order to decrease degradation by peptidases and yet retain affinity for and transport via hPEPT1. Seven structurally diverse N-methyl amide tripeptidomimetics were selected based on a principal component analysis of structural properties of 6859 N-methyl amide tripeptidomimetics. In vitro extracellular degradation of the selected tripeptidomimetics as well as affinity for and transepithelial transport via hPEPT1 were investigated in Caco-2 cells. Decreased apparent degradation was observed for all tripeptidomimetics compared to the corresponding natural tripeptides. However, affinity for and transepithelial transport via hPEPT1 were only seen for Gly-Sar-Sar, Asn Psi[CONCH3]Phe Psi[CONCH3]Trp, and Gly-Sar-Leu. This implies that tripeptidomimetics originating from tripeptides with neutral side chains are more likely to be substrates for hPEPT1 than tripeptidomimetics with charged side chains. The results of the present study indicate that the N-methyl amide peptide bond replacement approach for increasing bioavailability of tripeptidomimetic drug candidates is not generally applicable to all tripeptides. Nevertheless, retained affinity for and transport via hPEPT1 were shown for three of the evaluated N-methyl amide tripeptidomimetics. (c) 2006 Elsevier B.V All rights reserved.