(S)-methyl 2-((tert-butoxycarbonyl)(naphthalen-2-yl)methyl)acrylate | 1186668-59-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: (S)-methyl 2-((tert-butoxycarbonyl)(naphthalen-2-yl)methyl)acrylate
• 英文别名: methyl 2-[(S)-[(2-methylpropan-2-yl)oxycarbonylamino]-naphthalen-2-ylmethyl]prop-2-enoate
• CAS: 1186668-59-6
• 化学式: C₂₀H₂₃NO₄
• 分子量: 341.407
• InChiKey: WIKQNOYDEGNEAD-QGZVFWFLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  25
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  64.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (S)-methyl 2-((tert-butoxycarbonyl)(naphthalen-2-yl)methyl)acrylate 在 水 、 lithium hydroxide 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 12.0h， 以80%的产率得到(S)-2-(((tert-butoxycarbonyl)amino)(naphthalen-2-yl)methyl)acrylic acid
  参考文献：
  名称：

  A New Class of Highly Potent and Selective Endomorphin-1 Analogues Containing α-Methylene-β-aminopropanoic Acids (Map)

  摘要：

  A new class of endomorphin-1 (EM-1) analogues were synthesized by introduction of novel unnatural alpha-methylene-beta-amino acids (Map) at position 3 or/and position 4. Their binding and functional activity, metabolic stability, and antinociceptive activity were determined and compared. Most of these analogues showed high affinities for the mu-opioid receptor and an increased stability in mouse brain homogenates compared with EM-1. Examination of cAMP accumulation and ERK1/2 phosphorylation in HEK293 cells confirmed the agonist properties of these analogues. Among these new analogues, H-Tyr-Pro-Trp-(2-furyl)Map-NH2 (analogue 12) exhibited the highest binding potency (K-i(mu) = 0.221 nM) and efficacy (EC50 = 0.0334 nM, E-max = 97.14%). This analogue also displayed enhanced antinociceptive activity in vivo in comparison to EM-1. Molecular modeling approaches were then carried out to demonstrate the interaction pattern of these analogues with the opioid receptors. We found that, compared to EM-1, the incorporation of our synthesized Map at position 4 would bring the analogue to a closer binding mode with the mu-opioid receptor.

  DOI：

  10.1021/jm300664y
• 作为产物：
  描述：

  聚合甲醛 、 tert-butyl ((1S)-2-(dimethoxyphosphoryl)-1-(naphthalen-2-yl)-3-oxo-3-(1H-pyrrol-1-yl)propyl)carbamate 、 sodium methylate 在 甲醇 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 8.5h， 生成 (S)-methyl 2-((tert-butoxycarbonyl)(naphthalen-2-yl)methyl)acrylate
  参考文献：
  名称：

  A New Class of Highly Potent and Selective Endomorphin-1 Analogues Containing α-Methylene-β-aminopropanoic Acids (Map)

  摘要：

  A new class of endomorphin-1 (EM-1) analogues were synthesized by introduction of novel unnatural alpha-methylene-beta-amino acids (Map) at position 3 or/and position 4. Their binding and functional activity, metabolic stability, and antinociceptive activity were determined and compared. Most of these analogues showed high affinities for the mu-opioid receptor and an increased stability in mouse brain homogenates compared with EM-1. Examination of cAMP accumulation and ERK1/2 phosphorylation in HEK293 cells confirmed the agonist properties of these analogues. Among these new analogues, H-Tyr-Pro-Trp-(2-furyl)Map-NH2 (analogue 12) exhibited the highest binding potency (K-i(mu) = 0.221 nM) and efficacy (EC50 = 0.0334 nM, E-max = 97.14%). This analogue also displayed enhanced antinociceptive activity in vivo in comparison to EM-1. Molecular modeling approaches were then carried out to demonstrate the interaction pattern of these analogues with the opioid receptors. We found that, compared to EM-1, the incorporation of our synthesized Map at position 4 would bring the analogue to a closer binding mode with the mu-opioid receptor.

  DOI：

  10.1021/jm300664y

文献信息

• Catalytic Asymmetric Mannich Reactions of Sulfonylacetates
  作者：Carlo Cassani、Luca Bernardi、Francesco Fini、Alfredo Ricci

  DOI：10.1002/anie.200900701

  日期：2009.7.20

  synthetic equivalents of a variety of α‐carboxylate anions. Phase‐transfer catalysis (PTC) enabled their mild deprotonation and catalytic asymmetric addition to highly reactive imines generated in situ from α‐amidosulfones (see scheme; Pg=protecting group). The synthetic utility of the products was demonstrated by their straightforward transformation into a range of β‐amino acid derivatives.

  砜与砜：芳基磺酰乙酸盐可以看成是各种α-羧酸根阴离子的合成等价物。相转移催化（PTC）使它们能够轻度去质子化，并催化不对称添加到α-酰胺基砜现场生成的高反应性亚胺上（见方案； Pg =保护基）。通过将其直接转化为一系列β-氨基酸衍生物，证明了该产品的合成效用。
• A New Class of Highly Potent and Selective Endomorphin-1 Analogues Containing α-Methylene-β-aminopropanoic Acids (Map)
  作者：Yuan Wang、Yanhong Xing、Xin Liu、Hong Ji、Ming Kai、Zongyao Chen、Jing Yu、Depeng Zhao、Hui Ren、Rui Wang

  DOI：10.1021/jm300664y

  日期：2012.7.12

  A new class of endomorphin-1 (EM-1) analogues were synthesized by introduction of novel unnatural alpha-methylene-beta-amino acids (Map) at position 3 or/and position 4. Their binding and functional activity, metabolic stability, and antinociceptive activity were determined and compared. Most of these analogues showed high affinities for the mu-opioid receptor and an increased stability in mouse brain homogenates compared with EM-1. Examination of cAMP accumulation and ERK1/2 phosphorylation in HEK293 cells confirmed the agonist properties of these analogues. Among these new analogues, H-Tyr-Pro-Trp-(2-furyl)Map-NH2 (analogue 12) exhibited the highest binding potency (K-i(mu) = 0.221 nM) and efficacy (EC50 = 0.0334 nM, E-max = 97.14%). This analogue also displayed enhanced antinociceptive activity in vivo in comparison to EM-1. Molecular modeling approaches were then carried out to demonstrate the interaction pattern of these analogues with the opioid receptors. We found that, compared to EM-1, the incorporation of our synthesized Map at position 4 would bring the analogue to a closer binding mode with the mu-opioid receptor.