E-p-coumaryl alcohol ethyl ether | 957147-02-3

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂醇
• 英文名称: E-p-coumaryl alcohol ethyl ether
• 英文别名: (E)-3-(4-ethoxyphenyl)prop-2-en-1-ol；2-Propen-1-ol, 3-(4-ethoxyphenyl)-
• CAS: 957147-02-3
• 化学式: C₁₁H₁₄O₂
• 分子量: 178.231
• InChiKey: GFSWFUCBLILOSX-ONEGZZNKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  13
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  29.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  E-p-coumaryl alcohol ethyl ether 在 三溴化磷 、 potassium carbonate 作用下， 以 乙醚 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.17h， 生成 (E)-N-(chroman-7-ylmethyl)-N-methyl-3-(4-ethoxylphenyl)prop-2-en-1-amine hydrochloride
  参考文献：
  名称：

  Novel Inhibitors of Staphyloxanthin Virulence Factor in Comparison with Linezolid and Vancomycin versus Methicillin-Resistant, Linezolid-Resistant, and Vancomycin-Intermediate Staphylococcus aureus Infections in Vivo

  摘要：

  Our previous work (Wang et al. J. Med. Chem. 2016, 59, 4831-4848) revealed that effective benzocycloalkane-derived staphyloxanthin inhibitors against methicillin-resistant Staphylococcus aureus (S. aureus) infections were accompanied by poor water solubility and high hERG inhibition and dosages (preadministration). In this study, 92 chroman and coumaran derivatives as novel inhibitors have been addressed for overcoming deficiencies above. Derivatives 69 and 105 displayed excellent pigment inhibitory activities and low hERG inhibition, along with improvement of solubility by salt type selection. The broad and significantly potent antibacterial spectra of 69 and 105 were displayed first with normal administration in the livers and hearts in mice against pigmented S. aureus Newman, Mu50 (vancomycin-intermediate S. aureus), and NRS271 (linezolid-resistant S. aureus), compared with linezolid and vancomycin. In summary, both 69 and 105 have the potential to be developed as good antibacterial candidates targeting virulence factors.

  DOI：

  10.1021/acs.jmedchem.7b00949
• 作为产物：
  描述：

  反-4-乙氧基肉桂酸乙酯 在 二异丁基氢化铝 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 2.0h， 以1.52 g的产率得到E-p-coumaryl alcohol ethyl ether
  参考文献：
  名称：

  Intramolecular Povarov Reactions for the Synthesis of Chromenopyridine Fused 2-Pyridone Polyheterocycles Binding to α-Synuclein and Amyloid-β Fibrils

  摘要：

  A BF₃·OEt₂ catalyzed intramolecular Povarov reaction was used to synthesize 15 chromenopyridine fused thiazolino-2-pyridone peptidomimetics. The reaction works with several O-alkylated salicylaldehydes and amino functionalized thiazolino-2-pyridones, to generate polyheterocycles with diverse substitution. The synthesized compounds were screened for their ability to bind α-synuclein and amyloid β fibrils in vitro. Analogues substituted with a nitro group bind to mature amyloid fibrils, and the activity moreover depends on the positioning of this functional group.

  DOI：

  10.1021/acs.joc.0c01699

文献信息

• The enantioselective synthesis of APTO and AETD: polyhydroxylated β-amino acid constituents of the microsclerodermin cyclic peptides
  作者：Emily C. Shuter、Hung Duong、Craig A. Hutton、Malcolm D. McLeod

  DOI：10.1039/b707891a

  日期：——

  The polyhydroxylated beta-amino acids (2S,3R,4S,5S,7E)-3-amino-8-phenyl-2,4,5-trihydroxyoct-7-enoic acid (APTO) and (2S,3R,4S,5S,7E,9E)-3-amino-10-(4-ethoxyphenyl)-2,4,5-trihydroxydeca-7,9-dienoic acid (AETD) are key components of the microsclerodermin family of anti-fungal cyclic peptides. They have been synthesised in protected form in twelve steps using a unified strategy, with the introduction

  多羟基化的β-氨基酸（2S，3R，4S，5S，7E）-3-氨基-8-苯基-2,4,5-三羟基辛-7-烯酸（APTO）和（2S，3R，4S，5S ，7E，9E）-3-氨基-10-（4-乙氧基苯基）-2,4,5-三羟基癸-7,9-二烯酸（AETD）是抗真菌环状肽微菌皮家族的关键成分。它们已使用统一策略以十二个步骤以保护形式合成，并在合成的最后一步中从常见的醛中间体引入不饱和侧链。合成的特征是不对称氨基羟基化和二羟基化反应的有序应用，以高选择性有效地引入了靶标的立体化学。
• Novel Staphyloxanthin Inhibitors with Improved Potency against Multidrug Resistant <i>Staphylococcus aureus</i>
  作者：Shuaishuai Ni、Baoli Li、Feifei Chen、Hanwen Wei、Fei Mao、Yifu Liu、Yixiang Xu、Xiaoxi Qiu、Xiaokang Li、Wenwen Liu、Linghao Hu、Dazheng Ling、Manjiong Wang、Xinyu Zheng、Jin Zhu、Lefu Lan、Jian Li

  DOI：10.1021/acsmedchemlett.7b00501

  日期：2018.3.8

  Diapophytoene desaturase (CrtN) is a potential novel target for intervening in the biosynthesis of the virulence factor staphyloxanthin. In this study, 38 1,4-benzodioxan-derived CrtN inhibitors were designed and synthesized to overwhelm the defects of leading compound 4a. Derivative 47 displayed superior pigment inhibitory activity, better hERG inhibitory properties and water solubility, and significantly sensitized MRSA strains to immune clearance in vitro. Notably, 47 displayed excellent efficacy against pigmented S. aureus Newman, Mu50 (vancomycin-intermediate MRSA, VISA), and NRS271 (linezolid-resistant MRSA, LRSA) comparable to that of linezolid and vancomycin in vivo.
• Novel Terminal Bipheny-Based Diapophytoene Desaturases (CrtN) Inhibitors as Anti-MRSA/VISR/LRSA Agents with Reduced hERG Activity
  作者：Baoli Li、Shuaishuai Ni、Fei Mao、Feifei Chen、Yifu Liu、Hanwen Wei、Wenhua Chen、Jin Zhu、Lefu Lan、Jian Li

  DOI：10.1021/acs.jmedchem.7b01300

  日期：2018.1.11

  CrtN has been identified as an attractive and druggable target for treating pigmented Staphylococcus aureus infections. More than 100 new compounds were synthesized, which target the overwhelming the defects of the CrtN inhibitor 1. Analogues 23a and 23b demonstrated a significant activity against pigmented S. aureus Newman and 13 MRSA strains (IC50 = 0.02-10.5 nM), along with lower hERG inhibition (IC50 > 30 mu M, similar to 10-fold decrease in comparison with 1). Furthermore, 23a and 23b were confirmed to reduce the staphylococcal load in the kidney and heart in a mouse model with normal treatment deeper than pretreatment ones, comparable even with vancomycin and linezolid. Remarkably, 23a could strongly block the pigment biosynthesis of these nine multidrug-resistant MRSA strains, including excellent activity against LRSA strains and VISA strains in vivo, and all of which demonstrated that 23a has a huge potential against intractable MRSA, VISA, and LRSA issues as a therapeutic drug.
• Discovery of novel piperonyl derivatives as diapophytoene desaturase inhibitors for the treatment of methicillin-, vancomycin- and linezolid-resistant Staphylococcus aureus infections
  作者：Hanwen Wei、Fei Mao、Shuaishuai Ni、Feifei Chen、Baoli Li、Xiaoxia Qiu、Linghao Hu、Manjiong Wang、Xinyu Zheng、Jin Zhu、Lefu Lan、Jian Li

  DOI：10.1016/j.ejmech.2017.12.090

  日期：2018.2

  Inhibition of S. aureus diapophytoene desaturase (CrtN) could serve as an alternative approach for addressing the tricky antibiotic resistance by blocking the biosynthesis of carotenoid pigment which shields the bacterium from host oxidant killing. In this study, we designed and synthesized 44 derivatives with piperonyl scaffold targeting CrtN and the structure-activity relationships (SARs) were examined extensively to bring out the discovery of 21b with potent efficacy and better hERG safety profile compared to the first class CrtN inhibitor benzocycloalkane derivative 2. Except the excellent pigment inhibitory activity against wild-type S. aureus, 21b also showed excellent pigment inhibition against four pigmented MRSA strains. In addition, H2O2 killing and human whole blood killing assays proved 21b could sensitize S. aureus to be killed under oxidative stress conditions. Notably, the murine study in vivo validated the efficacy of 21b against pigmented S. aureus Newman, vancomycin-intermediate S. aureus Mu50 and linezolid-resistant S. aureus NRS271. (C) 2018 Elsevier Masson SAS. All rights reserved.
• Rapid Assembly of the Polyhydroxylated β-Amino Acid Constituents of Microsclerodermins C, D, and E
  作者：Thomas Hjelmgaard、Sophie Faure、Pascale Lemoine、Bernard Viossat、David J. Aitken

  DOI：10.1021/ol702962z

  日期：2008.3.1

  A very short and efficient synthesis of protected derivatives of APTO and AETD, the complex polyhydroxylated beta-amino acid residues present in microsclerodermins C, D, and E, is described. The targets are obtained in only five steps, in 23% and 16% overall yields, respectively. The key transformation involves the completely diastereoselective two-carbon homologation of appropriately selected intermediate chiral sulfinimines.