[(S)-2-((S)-2-Carbamoyl-pyrrolidin-1-yl)-1-(4-hydroxy-2,6-dimethyl-benzyl)-2-oxo-ethyl]-carbamic acid tert-butyl ester | 579491-20-6

• 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: [(S)-2-((S)-2-Carbamoyl-pyrrolidin-1-yl)-1-(4-hydroxy-2,6-dimethyl-benzyl)-2-oxo-ethyl]-carbamic acid tert-butyl ester
• CAS: 579491-20-6
• 化学式: C₂₁H₃₁N₃O₅
• 分子量: 405.494
• InChiKey: ZEYHWDDOYNWGAP-IRXDYDNUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.92
• 重原子数：
  29.0
• 可旋转键数：
  5.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  121.96
• 氢给体数：
  3.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  [(S)-2-((S)-2-Carbamoyl-pyrrolidin-1-yl)-1-(4-hydroxy-2,6-dimethyl-benzyl)-2-oxo-ethyl]-carbamic acid tert-butyl ester 在 盐酸 作用下， 以 1,4-二氧六环 为溶剂， 反应 1.0h， 以63.2%的产率得到(S)-1-[(S)-2-Amino-3-(4-hydroxy-2,6-dimethyl-phenyl)-propionyl]-pyrrolidine-2-carboxylic acid amide
  参考文献：
  名称：

  Structural studies of [2′,6′-dimethyl-l-tyrosine1]endomorphin-2 analogues: enhanced activity and cis orientation of the Dmt-Pro amide bond

  摘要：

  Analogues of endomorphin-2 (EM-2: Tyr-Pro-Phe-Phe-NH2) (1) were designed to examine the importance of each residue on mu-opioid receptor interaction. Replacement of Tyr(1) by 2',6'-dimethyl-L-tyrosine (Dmt) (9-12) exerted profound effects: [Dmt(1)]EM-2 (9) elevated mu-opioid affinity 4.6-fold (K(i)mu = 0.15 nM) yet selectivity fell 330-fold as delta-affinity rose (K(i)delta = 28.2 nM). This simultaneous increased mu- and delta-receptor bioactivities resulted in dual agonism (IC50 = 0.07 and 1.87 nM, respectively). While substitution of Phe(4) by a phenethyl group (4) decreased mu affinity (K(i)mu 13.3 nM), the same derivative containing Dmt (12) was comparable to EM-2 but also acquired weak delta antagonism (pA(2) = 7.05). H-1 NMR spectroscopy revealed a trans configuration (1:2 to 1:3, cis/trans) in the Tyr-Pro amide bond, but a cis configuration (5:3 to 13:7, cis/trans) with Dmt-Pro analogues. (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(03)00068-3
• 作为产物：
  描述：

  二碳酸二叔丁酯 在 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 三乙胺 、 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 、 水 、 N,N-二甲基甲酰胺 为溶剂， 生成 [(S)-2-((S)-2-Carbamoyl-pyrrolidin-1-yl)-1-(4-hydroxy-2,6-dimethyl-benzyl)-2-oxo-ethyl]-carbamic acid tert-butyl ester
  参考文献：
  名称：

  Structural studies of [2′,6′-dimethyl-l-tyrosine1]endomorphin-2 analogues: enhanced activity and cis orientation of the Dmt-Pro amide bond

  摘要：

  Analogues of endomorphin-2 (EM-2: Tyr-Pro-Phe-Phe-NH2) (1) were designed to examine the importance of each residue on mu-opioid receptor interaction. Replacement of Tyr(1) by 2',6'-dimethyl-L-tyrosine (Dmt) (9-12) exerted profound effects: [Dmt(1)]EM-2 (9) elevated mu-opioid affinity 4.6-fold (K(i)mu = 0.15 nM) yet selectivity fell 330-fold as delta-affinity rose (K(i)delta = 28.2 nM). This simultaneous increased mu- and delta-receptor bioactivities resulted in dual agonism (IC50 = 0.07 and 1.87 nM, respectively). While substitution of Phe(4) by a phenethyl group (4) decreased mu affinity (K(i)mu 13.3 nM), the same derivative containing Dmt (12) was comparable to EM-2 but also acquired weak delta antagonism (pA(2) = 7.05). H-1 NMR spectroscopy revealed a trans configuration (1:2 to 1:3, cis/trans) in the Tyr-Pro amide bond, but a cis configuration (5:3 to 13:7, cis/trans) with Dmt-Pro analogues. (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(03)00068-3