(S)-2-((S)-1-Benzylcarbamoyl-2-phenyl-ethylcarbamoyl)-pyrrolidine-1-carboxylic acid tert-butyl ester | 714970-03-3

• 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)-1-Benzylcarbamoyl-2-phenyl-ethylcarbamoyl)-pyrrolidine-1-carboxylic acid tert-butyl ester
• CAS: 714970-03-3
• 化学式: C₂₆H₃₃N₃O₄
• 分子量: 451.566
• InChiKey: OYCIIVHZMLLKHY-VXKWHMMOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.43
• 重原子数：
  33.0
• 可旋转键数：
  7.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  87.74
• 氢给体数：
  2.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  (S)-2-((S)-1-Benzylcarbamoyl-2-phenyl-ethylcarbamoyl)-pyrrolidine-1-carboxylic acid tert-butyl ester 在 盐酸 、 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 生成 H-Tyr(2,6-diMe)-Pro-Phe-NHBn
  参考文献：
  名称：

  Development of Potent Bifunctional Endomorphin-2 Analogues with Mixed μ-/δ-Opioid Agonist and δ-Opioid Antagonist Properties

  摘要：

  The C terminus of endomorphin-2 (EM-2) analogues (Tyr-Pro-Phe-NH-X) was modified with aromatic, heteroaromatic, or aliphatic groups (X = phenethyl,benzyl, phenyl, naphthyl, pyridyl, quinolyl, isoquinolyl, tert-butyl, cyclohexyl, or adamantyl; 3-18) to study their effect on opioid activity. Only 9 (1-naphthyl), 11 (5-quinolyl), 16 (cyclohexyl), and 18 (2-adamantyl) exhibited mu-opioid receptor affinity in the nanomolar range (K-i = 2.41-6.59 nM), which, however, was 3- to 10-fold less than the parent peptide. Replacement of Tyr(1) by Dmt (2',6'-dimethyl-L-tyrosine) (19-32) exerted profound effects: (i) acquisition of high mu-opioid receptor affinity (K-i = 0.11-0.52 nM) except 23 (Ph); (ii) presence of potent functional mu-opioid receptor agonism (IC50 < 1 nM) for 19 ([Dmt(1)]EM-2), 27 (1-naphthyl), 29 (5-quinolyl), and 32 (5-isolquinolyl); (iii) association of weak delta-opioid antagonist activity (pA(2) = 5.41-7.18) except 19 ([Dmt(1)]EM-2), 20 (H), 27 (1-naphthyl), and in particular 29 (5-quinolyl) with its potent delta-agonism (IC50 = 0.62 nM, pA(2) = 5.88); (iv) production of antinociception after ic administration of 32 (5-isoquinolyl) in mice, a bioactivity absent in the corresponding Tyr(1) analogue (14); and (v) preferential cis orientation (cis/trans = 3:2 to 7:3) at the Dmt-Pro amide bond, in contrast to the Tyr-Pro amide trans orientation (cis/trans = 1:2 to 1:3). Thus, [Dmt(1)]EM-2 analogues with hydrophobic C-terminal extensions provide model compounds with potent mu-opioid receptor bioactivity and dual functional agonism.

  DOI：

  10.1021/jm030649p
• 作为产物：
  描述：

  (S)-N-Boc-phenylalanine benzylamide 在 N-甲基吗啉 、 盐酸 、 氯甲酸异丁酯 作用下， 以 四氢呋喃 、 1,4-二氧六环 为溶剂， 生成 (S)-2-((S)-1-Benzylcarbamoyl-2-phenyl-ethylcarbamoyl)-pyrrolidine-1-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  Development of Potent Bifunctional Endomorphin-2 Analogues with Mixed μ-/δ-Opioid Agonist and δ-Opioid Antagonist Properties

  摘要：

  The C terminus of endomorphin-2 (EM-2) analogues (Tyr-Pro-Phe-NH-X) was modified with aromatic, heteroaromatic, or aliphatic groups (X = phenethyl,benzyl, phenyl, naphthyl, pyridyl, quinolyl, isoquinolyl, tert-butyl, cyclohexyl, or adamantyl; 3-18) to study their effect on opioid activity. Only 9 (1-naphthyl), 11 (5-quinolyl), 16 (cyclohexyl), and 18 (2-adamantyl) exhibited mu-opioid receptor affinity in the nanomolar range (K-i = 2.41-6.59 nM), which, however, was 3- to 10-fold less than the parent peptide. Replacement of Tyr(1) by Dmt (2',6'-dimethyl-L-tyrosine) (19-32) exerted profound effects: (i) acquisition of high mu-opioid receptor affinity (K-i = 0.11-0.52 nM) except 23 (Ph); (ii) presence of potent functional mu-opioid receptor agonism (IC50 < 1 nM) for 19 ([Dmt(1)]EM-2), 27 (1-naphthyl), 29 (5-quinolyl), and 32 (5-isolquinolyl); (iii) association of weak delta-opioid antagonist activity (pA(2) = 5.41-7.18) except 19 ([Dmt(1)]EM-2), 20 (H), 27 (1-naphthyl), and in particular 29 (5-quinolyl) with its potent delta-agonism (IC50 = 0.62 nM, pA(2) = 5.88); (iv) production of antinociception after ic administration of 32 (5-isoquinolyl) in mice, a bioactivity absent in the corresponding Tyr(1) analogue (14); and (v) preferential cis orientation (cis/trans = 3:2 to 7:3) at the Dmt-Pro amide bond, in contrast to the Tyr-Pro amide trans orientation (cis/trans = 1:2 to 1:3). Thus, [Dmt(1)]EM-2 analogues with hydrophobic C-terminal extensions provide model compounds with potent mu-opioid receptor bioactivity and dual functional agonism.

  DOI：

  10.1021/jm030649p

文献信息

• An investigation of chiral diamides as organocatalysts in asymmetric aldol reaction
  作者：Dilek Gul Yilmaz、Feray Aydogan、Cigdem Yolacan

  DOI：10.1002/jhet.4457

  日期：2022.7

  proline and 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (THIQA) based diamides were synthesized successfully by simple amidation reactions and characterized by their spectral data. Their catalytic activities in asymmetric aldol reaction were performed by the reactions of aliphatic ketones and various aromatic aldehydes. Especially, (S)-N-((S)-1-(morpholinoamino)-1-oxo-3-phenylpropan-2-yl)pyrrolidine-2-carboxamide

  通过简单的酰胺化反应成功合成了七种新型脯氨酸和 1,2,3,4-四氢异喹啉-3-羧酸 (THIQA) 基二酰胺，并通过其光谱数据进行了表征。它们在不对称羟醛反应中的催化活性是通过脂肪酮和各种芳香醛的反应进行的。特别是，( S ) -N -(( S )-1-(吗啉代氨基)-1-氧代-3-苯基丙-2-基)吡咯烷-2-甲酰胺( 9e) 在苯甲酸助催化剂存在下，在室温下在水中表现出良好的催化活性。对映选择性高达89.6%，非对映体比高达92/8，收率高达97.3%。该催化剂在水中表现出最好的催化活性；这也是对绿色化学要求的重要贡献。