N-Benzyloxycarbonyl-glycyl-glycyl-L-phenylalanyl-L-leucin-methylester | 68835-85-8

• 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: N-Benzyloxycarbonyl-glycyl-glycyl-L-phenylalanyl-L-leucin-methylester
• 英文别名: N-benzyloxycarbonyl-glycyl-glycyl-(S)phenylalanyl-(S)leucine methyl ester；N-Benzyloxycarbonyl-glycyl-glycyl-(S)-phenylalanyl-(S)-leucinmethylester；N-Cbz-Gly-Gly-Phe-Leu-OMe；Cbz-Gly-Gly-Phe-Leu-OMe；methyl (2S)-4-methyl-2-[[(2S)-3-phenyl-2-[[2-[[2-(phenylmethoxycarbonylamino)acetyl]amino]acetyl]amino]propanoyl]amino]pentanoate
• CAS: 68835-85-8
• 化学式: C₂₈H₃₆N₄O₇
• 分子量: 540.616
• InChiKey: ZOQVLQVBHRNIBH-GOTSBHOMSA-N

物化性质

• 沸点：
  833.1±65.0 °C(Predicted)
• 密度：
  1.204±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  39
• 可旋转键数：
  16
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  152
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  N-Benzyloxycarbonyl-glycyl-glycyl-L-phenylalanyl-L-leucin-methylester 在 palladium on activated charcoal 盐酸 、 氢气 作用下， 以 甲醇 为溶剂， 以57%的产率得到Glycyl-glycyl-(S)-phenylalanyl-(S)-leucinmethylesterhydrochlorid
  参考文献：
  名称：

  氨基酸。8. Mitt. 用 (±) 5-hydroxy-2-pyridylglycine ((±) Pyg (5-OH)) 合成肽，这是一种新的杂环取代氨基酸

  摘要：

  使用新的杂环取代氨基酸 Pyg (5-OH) (3) 进行肽合成，目的是合成 (Leu5)-脑啡肽衍生物，其中 Tyr 被 Pyg (5-OH) 取代。

  DOI：

  10.1002/ardp.19873200612
• 作为产物：
  描述：

  甲基N-[(苄氧基)羰基]甘氨酰甘氨酸酸酯 在 氯甲酸乙酯 、 三乙胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 水 、 丙酮 为溶剂， 反应 26.5h， 生成 N-Benzyloxycarbonyl-glycyl-glycyl-L-phenylalanyl-L-leucin-methylester
  参考文献：
  名称：

  Rational Design of Small Peptides for Optimal Inhibition of Cyclooxygenase-2: Development of a Highly Effective Anti-Inflammatory Agent

  摘要：

  Among the small peptides 2-31, (H)Gly-Gly-Phe-Leu(OMe) (30) reduced prostaglandin production of COX-2 with an IC50 of 60 nM relative to 6000 nM for COX-1. The 5 mg kg-1 dose of compound 30 rescued albino mice by 80% from capsaicin-induced paw licking and recovered it by 60% from carrageenan-induced inflammation. The mode of action of compound 30 for targeting COX-2, iNOS, and VGSC was investigated by using substance P, l-arginine, and veratrine, respectively, as biomarkers. The interactions of 30 with COX-2 were supported by isothermal calorimetry experiments showing a Ka of 6.10 +/- 1.10 X 104 M-1 and Delta G of -100.3 kJ mol-1 in comparison to a Ka 0.41 X 103 +/- 0.09 M-1 and Delta G of -19.2 +/- 0.06 kJ mol(-1) for COX-1. Moreover, compound 30 did not show toxicity up to a 2000 mg kg(-1) dose. Hence, we suggest peptide 30 as a highly potent and promising candidate for further development into an anti-inflammatory drug.

  DOI：

  10.1021/acs.jmedchem.6b00134

文献信息

• über Aminosäuren und Peptide, 50. Über aktivierteN, N-Dimethylaminosäuren. – Synthese von Enkephalinen mitN,N-Dimethyltyrosin
  作者：Ulrich Schmidt、Karin Schefenacker

  DOI：10.1002/jlac.198519850615

  日期：1985.6.12

  Zur Aktivierung von N, N-Dimethylaminosäuren beim Aufbau von N,N-Dimethylpeptiden sind die Ester des 3-Cyan-4,6-dimethyl-2-pyridinthiols allen anderen untersuchten Aminosäurederivaten überlegen. Mit ihrer Hilfe ließen sich N,N-Dimethyl-Enkephaline ohne Epimerisierung aufbauen.

  3-氰基-4，6-二甲基-2-吡啶硫醇的酯在形成N，N-二甲基肽时，在活化N，N-二甲基氨基酸方面优于所有其他研究的氨基酸衍生物。在它们的帮助下，可以在没有差向异构的情况下构建N，N-二甲基脑啡肽。
• Diastereoselective hydrogenation of monodehydro enkephalins controlled by chiral rhodium catalysts
  作者：A. Hammadi、J.M. Nuzillard、J.C. Poulin、H.B. Kagan

  DOI：10.1016/s0957-4166(00)82083-2

  日期：1992.10

  Protected (Z)dehydrophenylalanyl-Leu-enkephalin, (Z)dehydrotyrosyl-Leu-enkephalin and (Z)dehydrotyrosyl-(R)Ala2-Leu-enkephalin, have been synthesized. These compounds have been hydrogenated to give protected Leu-enkephalins in the presence of various chiral rhodium complexes. Deprotection of the product gave Leu-enkephalins or epimers, ytterbium in liquid ammonia allows smooth deprotection of NHCBz or OTs groups on small amounts of peptides. Strong stereocontrol could be achieved by suitable choice of the chiral catalyst. This method has good potential for stereospecific labelling of enkephalins and other small peptides.
• Rational Design of Small Peptides for Optimal Inhibition of Cyclooxygenase-2: Development of a Highly Effective Anti-Inflammatory Agent
  作者：Palwinder Singh、Sukhmeet Kaur、Jagroop Kaur、Gurjit Singh、Rajbir Bhatti

  DOI：10.1021/acs.jmedchem.6b00134

  日期：2016.4.28

  Among the small peptides 2-31, (H)Gly-Gly-Phe-Leu(OMe) (30) reduced prostaglandin production of COX-2 with an IC50 of 60 nM relative to 6000 nM for COX-1. The 5 mg kg-1 dose of compound 30 rescued albino mice by 80% from capsaicin-induced paw licking and recovered it by 60% from carrageenan-induced inflammation. The mode of action of compound 30 for targeting COX-2, iNOS, and VGSC was investigated by using substance P, l-arginine, and veratrine, respectively, as biomarkers. The interactions of 30 with COX-2 were supported by isothermal calorimetry experiments showing a Ka of 6.10 +/- 1.10 X 104 M-1 and Delta G of -100.3 kJ mol-1 in comparison to a Ka 0.41 X 103 +/- 0.09 M-1 and Delta G of -19.2 +/- 0.06 kJ mol(-1) for COX-1. Moreover, compound 30 did not show toxicity up to a 2000 mg kg(-1) dose. Hence, we suggest peptide 30 as a highly potent and promising candidate for further development into an anti-inflammatory drug.
• Aminosäuren. 8. Mitt. Peptidsynthesen mit (±) 5-Hydroxy-2-pyridylglycin ((±) Pyg (5-OH)), einer neuen heterocyclisch substituierten Aminosäure
  作者：Claus Herdeis、Rolf Gebhard

  DOI：10.1002/ardp.19873200612

  日期：——

  Peptidsynthesen mit der neuen heterocyclisch substituierten Aminosäure Pyg(5‐OH) (3) werden durchgeführt mit dem Ziel, ein (Leu5)‐Enkephalinderivat zu synthetisieren, in dem Tyr durch Pyg(5‐OH) ersetzt ist.

  使用新的杂环取代氨基酸 Pyg (5-OH) (3) 进行肽合成，目的是合成 (Leu5)-脑啡肽衍生物，其中 Tyr 被 Pyg (5-OH) 取代。