(2S,5S,8S,11S)-11-acetamido-5-(3-amino-3-oxopropyl)-2-(2-(tert-butoxy)-2-oxoethyl)-15,15-dimethyl-8-(2-(methylthio)ethyl)-4,7,10,13-tetraoxo-14-oxa-3,6,9-triazahexadecanoic acid | 1007603-74-8

• 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: (2S,5S,8S,11S)-11-acetamido-5-(3-amino-3-oxopropyl)-2-(2-(tert-butoxy)-2-oxoethyl)-15,15-dimethyl-8-(2-(methylthio)ethyl)-4,7,10,13-tetraoxo-14-oxa-3,6,9-triazahexadecanoic acid
• CAS: 1007603-74-8
• 化学式: C₂₈H₄₇N₅O₁₁S
• 分子量: 661.774
• InChiKey: RBXRYAPTVRUDTH-VJANTYMQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.49
• 重原子数：
  45.0
• 可旋转键数：
  18.0
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  249.39
• 氢给体数：
  6.0
• 氢受体数：
  11.0

反应信息

• 作为反应物：
  描述：

  7-氨基-4-甲基香豆素 、 (2S,5S,8S,11S)-11-acetamido-5-(3-amino-3-oxopropyl)-2-(2-(tert-butoxy)-2-oxoethyl)-15,15-dimethyl-8-(2-(methylthio)ethyl)-4,7,10,13-tetraoxo-14-oxa-3,6,9-triazahexadecanoic acid 在 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 120.0h， 生成 tert-butyl (4S,7S,10S,13S)-10-(3-amino-3-oxopropyl)-4-(2-(tert-butoxy)-2-oxoethyl)-13-((4-methyl-2-oxo-2H-chromen-7-yl)carbamoyl)-7-(2-(methylthio)ethyl)-2,5,8,11-tetraoxo-3,6,9,12-tetraazapentadecan-15-oate 、 tert-butyl (4S,7S,10S,13R)-10-(3-amino-3-oxopropyl)-4-(2-(tert-butoxy)-2-oxoethyl)-13-((4-methyl-2-oxo-2H-chromen-7-yl)carbamoyl)-7-(2-(methylthio)ethyl)-2,5,8,11-tetraoxo-3,6,9,12-tetraazapentadecan-15-oate
  参考文献：
  名称：

  Control of aspartate epimerization during the coupling of caspase specific tetrapeptides with aromatic amines by using N-[[(dimethylamino)-1H-1,2,3-triazolo[4,5-b]-pyridin-1-yl]methylene]-N-methylmethanaminium hexafluorophosphate N-oxide (HATU) as a coupling reagent

  摘要：

  During the synthesis of new caspase substrates, we have encountered extensive aspartate epimerization upon coupling of t-Bu-protected tetrapeptides Ac-IETD-OH or Ac-DMQD-OH with aromatic amines (aminocoumarins and aminoquinolines) by using aminium-based coupling reagent HATU in the presence of 2,4,6-trimethylpyridine (TMP). To study this reaction in more detail, an RP-HPLC method was developed that afforded the separation of the epimers. By carefully adjusting the reaction conditions, the epimerization could be reduced to very small levels (from 75% down to below 3%). A new, highly hindered base 2,4,6-tri-tert-butyl-pyridine (TBP), was found to be superior to the traditional TMP in the catalysis of this reaction. Moreover, the aspartate epimers were found to be interconvertable at elevated temperatures in an inert solvent, whereby the D-aspartate containing epimer was the thermodynamically controlled product. Over the Course of the study, new side products of HATU coupling reactions, the N,N-dimethylamides of the aspartic residue of above tetrapeptides, were also identified. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetasy.2007.11.036
• 作为产物：
  描述：

  alkaline earth salt of/the/ methylsulfuric acid 在 溶剂黄146 作用下， 以 二氯甲烷 、 2,2,2-三氟乙醇 为溶剂， 反应 0.5h， 以94%的产率得到(2S,5S,8S,11S)-11-acetamido-5-(3-amino-3-oxopropyl)-2-(2-(tert-butoxy)-2-oxoethyl)-15,15-dimethyl-8-(2-(methylthio)ethyl)-4,7,10,13-tetraoxo-14-oxa-3,6,9-triazahexadecanoic acid
  参考文献：
  名称：

  Control of aspartate epimerization during the coupling of caspase specific tetrapeptides with aromatic amines by using N-[[(dimethylamino)-1H-1,2,3-triazolo[4,5-b]-pyridin-1-yl]methylene]-N-methylmethanaminium hexafluorophosphate N-oxide (HATU) as a coupling reagent

  摘要：

  During the synthesis of new caspase substrates, we have encountered extensive aspartate epimerization upon coupling of t-Bu-protected tetrapeptides Ac-IETD-OH or Ac-DMQD-OH with aromatic amines (aminocoumarins and aminoquinolines) by using aminium-based coupling reagent HATU in the presence of 2,4,6-trimethylpyridine (TMP). To study this reaction in more detail, an RP-HPLC method was developed that afforded the separation of the epimers. By carefully adjusting the reaction conditions, the epimerization could be reduced to very small levels (from 75% down to below 3%). A new, highly hindered base 2,4,6-tri-tert-butyl-pyridine (TBP), was found to be superior to the traditional TMP in the catalysis of this reaction. Moreover, the aspartate epimers were found to be interconvertable at elevated temperatures in an inert solvent, whereby the D-aspartate containing epimer was the thermodynamically controlled product. Over the Course of the study, new side products of HATU coupling reactions, the N,N-dimethylamides of the aspartic residue of above tetrapeptides, were also identified. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetasy.2007.11.036