(S)-N-(2-oxo-tetrahydrofuran-3-yl)-2-phenylacetamide

• 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)-N-(2-oxo-tetrahydrofuran-3-yl)-2-phenylacetamide
• 英文别名: N-2-phenylethanoyl-L-homoserine lactone；phenylacetyl-homoserine lactone；(S)-(-)-α-N-phenylacetamido-γ-butyrolactone；2-phenylethanoyl-L-HSL；N-phenylacetyl-L-Homoserine lactone；N-[(3S)-2-oxooxolan-3-yl]-2-phenylacetamide
• 化学式: C₁₂H₁₃NO₃
• 分子量: 219.24
• InChiKey: YJTHUPUWKQRCLF-JTQLQIEISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  55.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (S)-N-(2-oxo-tetrahydrofuran-3-yl)-2-phenylacetamide 在 盐酸 、 水 作用下， 反应 6.0h， 以100%的产率得到(S)-α-氨基-γ-丁内酯 盐酸盐
  参考文献：
  名称：

  Chemo-enzymatic synthesis of the azasugars 1,4-dideoxyallonojirimycin and 1,4-dideoxymannojirimycin

  摘要：

  The enzymatic resolution of the N-phenylacetyl derivative of racemic homoserine lactone with penicillin G acylase immobilized on Eupergit C gave (R)-(+)-alpha-amino-gamma-butyrolactone and (S)-(-)-alpha-N-phenylacetamido-gamma-butyrolactone in high enantiomeric purity (ee >99%) and 46-47% yields for each enantiomer. The enantiomers were converted into azasugars 1,4-dideoxyallonojirimycin and 1,4-dideoxymannojirimycin using Wittig olefination, catalytic ring-closing metathesis (RCM), and stereoselective dihydroxylation with OsO4 in 29% overall yield over 11 high yielding steps. Enzyme inhibition studies showed that 1,4-dideoxyallonojirimycin is a better beta-glucosidase inhibitor (IC50 32.4 mu M toward beta-glucosidase from almonds) and a better beta-galactosidase inhibitor (IC50 5.9 mM for beta-galactosidase from Aspergillus oryzae) than 1,4-dideoxymannojirimycin (IC50 2.86 mM and 12.5 mM for beta-glucosidase and beta-galactosidase, respectively). (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetasy.2011.10.015
• 作为产物：
  描述：

  在 三氟乙酸 作用下， 反应 18.0h， 生成 (S)-N-(2-oxo-tetrahydrofuran-3-yl)-2-phenylacetamide
  参考文献：
  名称：

  使用小分子宏阵列有效合成和评估群体感应调制器

  摘要：

  报道了一种合成N-酰化l-高丝氨酸内酯 (AHL)小分子微阵列的方法。构建了一个重点 AHL 库，并发现宏阵列平台与使用群体感应 (QS) 报告菌株的溶液和琼脂覆盖测定兼容。发现了几种 QS 拮抗剂，并用于展示宏阵列作为 QS 研究的直接技术。

  DOI：

  10.1021/ol901871y

文献信息

• Microwave Synthesis and Evaluation of Phenacylhomoserine Lactones as Anticancer Compounds that Minimally Activate Quorum Sensing Pathways in <i>Pseudomonas aeruginosa</i>
  作者：Colin M. Oliver、Amy L. Schaefer、E. Peter Greenberg、Janice R. Sufrin

  DOI：10.1021/jm8015377

  日期：2009.3.26

  compromises further consideration as a potential anticancer agent. In search of acylhomoserine lactones that selectively inhibit cancer cell growth, a library of phenacylhomoserine lactone analogues has been prepared by microwave synthesis and evaluated for cancer growth inhibition and quorum sensing activation. Comparative SAR analysis demonstrates that both anticancer and QS signaling systems require long

  细菌群体感应（QS）信号分子3-氧代-十二烷酰基-1-高丝氨酸内酯（OdDHL）由机会病原体铜绿假单胞菌产生，并控制与免疫受损个体中威胁生命的感染相关的毒力因子的表达。OdDHL还显示出抗癌活性，但具有增强铜绿假单胞菌致病性的能力。作为潜在的抗癌药，需要进一步考虑。为了寻找选择性抑制癌细胞生长的酰基高丝氨酸内酯，已通过微波合成制备了苯甲基高丝氨酸内酯类似物的文库，并评估了其对癌症生长的抑制作用和群体感应激活。SAR对比分析表明，抗癌和QS信号系统均需要长酰基侧链，并带有3-氧代取代基才能发挥最大活性。化合物12b 3-氧代-12-苯基十二烷酰基-1-高丝氨酸内酯被鉴定为具有强大的癌症生长抑制活性的前导化合物，该活性使铜绿假单胞菌报道基因分析中QS信号通路的激活最小化。
• Compound Combinations for Attenuation of Bacterial Virulence
  申请人：WISCONSIN ALUMNI RESEARCH FOUNDATION

  公开号：US20170231962A1

  公开（公告）日：2017-08-17

  Methods for modulating quorum sensing in certain Gram-negative bacteria having multiple QS systems including Las, Rhl, and Pqs with associated receptors (LasR, RhlR and PqsR) which are modulated by small molecule modulators, particularly non-native modulators. Certain combinations of modulators of Las, Rhl and Pqs exhibit improved inhibition of virulence in comparison to the respective individual modulators. In particular, certain combinations of modulators exhibit improved inhibition in nutritionally depleted environments. More specifically, certain combinations of modulators exhibit improved inhibition in environments depleted in phosphate and/or environments depleted in iron. Nutrient depleted environments can mimic environments associated with bacterial infection in humans and non-human animals. The methods are useful in particular for modulating QS in Pseudomonas and Buckholderia.

  在某些具有多个QS系统的革兰氏阴性细菌中，包括具有相关受体（LasR、RhlR和PqsR）的Las、Rhl和Pqs的调控方法，这些受体受小分子调节剂（尤其是非天然调节剂）的调节。Las、Rhl和Pqs的某些调节剂组合相比于各自的单个调节剂表现出对毒力的改善抑制。特别是，某些调节剂组合在营养匮乏环境中表现出改善的抑制作用。更具体地说，某些调节剂组合在缺乏磷酸盐和/或缺乏铁的环境中表现出改善的抑制作用。营养匮乏环境可以模拟与人类和非人类动物细菌感染相关的环境。这些方法特别适用于调节假单胞菌和布氏杆菌中的QS。
• WO2008/116029
  申请人：——

  公开号：——

  公开（公告）日：——
• Modulation of Bacterial Quorum Sensing With Synthetic Ligands
  申请人：WISCONSIN ALUMNI RESEARCH FOUNDATION

  公开号：US20200115356A1

  公开（公告）日：2020-04-16

  The present invention provides compounds and methods for modulation of the quorum sensing of bacteria. In an embodiment, the compounds of the present invention are able to act as replacements for naturally occurring bacterial quorum sensing ligands in a ligand-protein binding system; that is, they imitate the effect of natural ligands and produce an agonistic effect. In another embodiment, the compounds of the present invention are able to act in a manner which disturbs or inhibits the naturally occurring ligand-protein binding system in quorum sensing bacteria; that is, they produce an antagonistic effect. The compounds of the present invention comprise N-acylated-homoserine lactones (AHLs) comprised of a wide range of acyl groups.
• MODULATION OF BACTERIAL QUORUM SENSING WITH SYNTHETIC LIGANDS
  申请人：WISCONSIN ALUMNI RESEARCH FOUNDATION

  公开号：US20220411390A1

  公开（公告）日：2022-12-29

  The present invention provides compounds and methods for modulation of the quorum sensing of bacteria. In an embodiment, the compounds of the present invention are able to act as replacements for naturally occurring bacterial quorum sensing ligands in a ligand-protein binding system; that is, they imitate the effect of natural ligands and produce an agonistic effect. In another embodiment, the compounds of the present invention are able to act in a manner which disturbs or inhibits the naturally occurring ligand-protein binding system in quorum sensing bacteria; that is, they produce an antagonistic effect. The compounds of the present invention comprise N-acylated-homoserine lactones (AHLs) comprised of a wide range of acyl groups.