(R)-1-allyl 5-tert-butyl 2-((tertbutoxycarbonyl)amino)pentanedioate | 1269619-44-4

• 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: (R)-1-allyl 5-tert-butyl 2-((tertbutoxycarbonyl)amino)pentanedioate
• 英文别名: 5-O-tert-butyl 1-O-prop-2-enyl (2R)-2-[(2-methylpropan-2-yl)oxycarbonylamino]pentanedioate
• CAS: 1269619-44-4
• 化学式: C₁₇H₂₉NO₆
• 分子量: 343.42
• InChiKey: OAMKDHLKBMYSED-GFCCVEGCSA-N

物化性质

• 沸点：
  427.7±40.0 °C(Predicted)
• 密度：
  1.060±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  24
• 可旋转键数：
  12
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  90.9
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (R)-1-allyl 5-tert-butyl 2-((tertbutoxycarbonyl)amino)pentanedioate 在 sodium carbonate 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 17.0h， 生成 N-[芴甲氧羰基]-D-谷氨酸烯丙基酯
  参考文献：
  名称：

  Structure−Activity Relationships in Nucleotide Oligomerization Domain 1 (Nod1) Agonistic γ-Glutamyldiaminopimelic Acid Derivatives

  摘要：

  N-Acyl-gamma-glutamyldiaminopimelic acid is a prototype ligand for Nod1. We report a detailed SAR of C-12-gamma-D-Glu-DAP. Analogues with glutaric or gamma-aminobutyric acid replacing the glutamic acid show greatly attenuated Nod1-agonistic activity. Substitution of the meso-diaminopimelic (DAP) acid component with monoaminopirnelic acid, L- or D-lysine, or cadaverine also results in reduced activity. The free amine on DAP is crucial. However, the N-acyl group on the D-glutamyl residue can be substituted with N-alkyl groups with full preservation of activity. The free carboxylates on the DAP and Glu components can also be esterified, resulting in more lipophilic but active analogues. Transcriptomal profiling showed a dominant up-regulation of IL-19, IL-20, IL-22, and IL-24, which may explain the pronounced Th2-polarizing activity of these compounds and also implicate cell signaling mediated by TREM-1. These results may explain the hitherto unknown mechanism of synergy between Nod1 and TLR agonists and are likely to be useful in designing vaccine adjuvants.

  DOI：

  10.1021/jm101535e
• 作为产物：
  描述：

  BOC-D-谷氨酸5-叔丁酯 、 烯丙醇 在 4-二甲氨基吡啶 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 以90%的产率得到(R)-1-allyl 5-tert-butyl 2-((tertbutoxycarbonyl)amino)pentanedioate
  参考文献：
  名称：

  Structure−Activity Relationships in Nucleotide Oligomerization Domain 1 (Nod1) Agonistic γ-Glutamyldiaminopimelic Acid Derivatives

  摘要：

  N-Acyl-gamma-glutamyldiaminopimelic acid is a prototype ligand for Nod1. We report a detailed SAR of C-12-gamma-D-Glu-DAP. Analogues with glutaric or gamma-aminobutyric acid replacing the glutamic acid show greatly attenuated Nod1-agonistic activity. Substitution of the meso-diaminopimelic (DAP) acid component with monoaminopirnelic acid, L- or D-lysine, or cadaverine also results in reduced activity. The free amine on DAP is crucial. However, the N-acyl group on the D-glutamyl residue can be substituted with N-alkyl groups with full preservation of activity. The free carboxylates on the DAP and Glu components can also be esterified, resulting in more lipophilic but active analogues. Transcriptomal profiling showed a dominant up-regulation of IL-19, IL-20, IL-22, and IL-24, which may explain the pronounced Th2-polarizing activity of these compounds and also implicate cell signaling mediated by TREM-1. These results may explain the hitherto unknown mechanism of synergy between Nod1 and TLR agonists and are likely to be useful in designing vaccine adjuvants.

  DOI：

  10.1021/jm101535e

文献信息

• Structure−Activity Relationships in Nucleotide Oligomerization Domain 1 (Nod1) Agonistic γ-Glutamyldiaminopimelic Acid Derivatives
  作者：Geetanjali Agnihotri、Rehman Ukani、Subbalakshmi S. Malladi、Hemamali J. Warshakoon、Rajalakshmi Balakrishna、Xinkun Wang、Sunil A. David

  DOI：10.1021/jm101535e

  日期：2011.3.10

  N-Acyl-gamma-glutamyldiaminopimelic acid is a prototype ligand for Nod1. We report a detailed SAR of C-12-gamma-D-Glu-DAP. Analogues with glutaric or gamma-aminobutyric acid replacing the glutamic acid show greatly attenuated Nod1-agonistic activity. Substitution of the meso-diaminopimelic (DAP) acid component with monoaminopirnelic acid, L- or D-lysine, or cadaverine also results in reduced activity. The free amine on DAP is crucial. However, the N-acyl group on the D-glutamyl residue can be substituted with N-alkyl groups with full preservation of activity. The free carboxylates on the DAP and Glu components can also be esterified, resulting in more lipophilic but active analogues. Transcriptomal profiling showed a dominant up-regulation of IL-19, IL-20, IL-22, and IL-24, which may explain the pronounced Th2-polarizing activity of these compounds and also implicate cell signaling mediated by TREM-1. These results may explain the hitherto unknown mechanism of synergy between Nod1 and TLR agonists and are likely to be useful in designing vaccine adjuvants.