(S)-2-(((tert-butoxycarbonyl)amino)(phenyl)methyl)acrylic acid | 186371-25-5

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 苯丙酸
• 英文名称: (S)-2-(((tert-butoxycarbonyl)amino)(phenyl)methyl)acrylic acid
• 英文别名: 2-[(S)-[(2-methylpropan-2-yl)oxycarbonylamino]-phenylmethyl]prop-2-enoic acid
• CAS: 186371-25-5
• 化学式: C₁₅H₁₉NO₄
• 分子量: 277.32
• InChiKey: HUQLIOFTOCSHHO-GFCCVEGCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  20
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  75.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (S)-2-(((tert-butoxycarbonyl)amino)(phenyl)methyl)acrylic acid 在 4-二甲氨基吡啶 、 四氧化锇 、 十二/十四烷基二甲基氧化胺 、 铜 、 N,N'-二环己基碳二亚胺 、 锌 作用下， 以 甲醇 、 水 、 溶剂黄146 、 甲苯 、 叔丁醇 为溶剂， 反应 72.5h， 生成 (3'S)-2'-Hydroxymethyldocetaxel
  参考文献：
  名称：

  Effective enantioselective approach to α-aminoalkylacrylic acid derivatives via a synthetic equivalent of an asymmetric Baylis–Hillman reaction: application to the synthesis of two C-2′ hydroxymethyl analogues of docetaxel

  摘要：

  Two C-2' hydroxymethyl analogues of docetaxel have been synthesized from 10-desacetyl baccatin III and enantiopure (3S)-3-(N-tert-butoxycarbonylamino)-2-methylene-3- phenylpropanoic acid; the latter was prepared vip the use of a new method, which is discussed, as is the biological evaluation of the two new analogues.

  DOI：

  10.1039/p19960002869
• 作为产物：
  描述：

  tert-butyl N-[(1S)-2-dimethoxyphosphoryl-3-oxo-1-phenyl-3-pyrrol-1-ylpropyl]carbamate 在 甲醇 、 水 、 lithium hydroxide 作用下， 以 四氢呋喃 为溶剂， 反应 20.5h， 生成 (S)-2-(((tert-butoxycarbonyl)amino)(phenyl)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

文献信息

• 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.
• Design, Synthesis, and Pharmacological Characterization of Novel Endomorphin-1 Analogues as Extremely Potent μ-Opioid Agonists
  作者：Xin Liu、Yuan Wang、Yanhong Xing、Jing Yu、Hong Ji、Ming Kai、Zilong Wang、Dan Wang、Yixin Zhang、Depeng Zhao、Rui Wang

  DOI：10.1021/jm400195y

  日期：2013.4.11

  Recently we reported the synthesis and structure activity study of endomorphin-1 (EM-1) analogues containing novel, unnatural alpha-methylene-beta-aminopropanoic acids (Map). In the present study, we describe new EM-1 analogues containing Dmt(1), (R/S)-beta Pro(2), and (ph)Map(4)/(2-furyl)Map(4). All of the analogues showed a high affinity for the mu-opioid receptor (MOR) and increased stability in mouse brain homogenates. Of the new compounds, Dmt(1)-(R)-beta Pro(2)-Trp(3)-(2-furyl)Map(4) (analogue 12) displayed the highest affinity toward MOR, in the picomolar range (K-i(mu) = 3.72 pM). Forskolin-induced cAMP accumulation assays indicated that this analogue displayed an extremely high agonistic potency, in the subpicomolar range (EC50 = 0.0421 pM, E-max = 99.5%). This compound also displayed stronger in vivo antinociceptive activity after iv administration when compared to morphine in the tail-flick test, which indicates that this analogue was able to cross the blood-brain barrier.
• Effective enantioselective approach to α-aminoalkylacrylic acid derivatives via a synthetic equivalent of an asymmetric Baylis–Hillman reaction: application to the synthesis of two C-2′ hydroxymethyl analogues of docetaxel
  作者：Yves Génisson、Christine Massardier、Isabelle Gautier-Luneau、Andrew E. Greene

  DOI：10.1039/p19960002869

  日期：——

  Two C-2' hydroxymethyl analogues of docetaxel have been synthesized from 10-desacetyl baccatin III and enantiopure (3S)-3-(N-tert-butoxycarbonylamino)-2-methylene-3- phenylpropanoic acid; the latter was prepared vip the use of a new method, which is discussed, as is the biological evaluation of the two new analogues.