(2S)-2-[[(1,1-Dimethylethyl)dimethylsilyl]oxy]butanoic acid | 1079843-58-5

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: (2S)-2-[[(1,1-Dimethylethyl)dimethylsilyl]oxy]butanoic acid
• 英文别名: (2S)-2-[tert-butyl(dimethyl)silyl]oxybutanoic acid
• CAS: 1079843-58-5
• 化学式: C₁₀H₂₂O₃Si
• 分子量: 218.368
• InChiKey: IYAKUMSVAGKDRS-QMMMGPOBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.87
• 重原子数：
  14.0
• 可旋转键数：
  4.0
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.9
• 拓扑面积：
  46.53
• 氢给体数：
  1.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  (2S)-2-[[(1,1-Dimethylethyl)dimethylsilyl]oxy]butanoic acid 在 氯化亚砜 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 18.0h， 生成 (S)-3-(tert-butyldimethylsilyloxy)decan-4-one
  参考文献：
  名称：

  Small molecule probes of the receptor binding site in the Vibrio cholerae CAI-1 quorum sensing circuit

  摘要：

  Based on modification of separate structural features of the Vibrio cholerae quorum sensing signal, (S)-3-hydroxytridecan-4-one (CAI-1), three focused compound libraries have been synthesized and evaluated for biological activity. Modifications to the acyl tail and alpha-hydroxy ketone typically provided agonists with activities correlated to tail length and conservative changes to the hydroxy ketone. Among the molecules identified within this collection of agonists is Am-CAI-1 (B11), which is among the most potent agonists reported to date with an EC50 of 0.21 mu M. Modifications to the ethyl side chain delivered molecules with both agonist and antagonist activity, including m-OH-Ph-CAI-1 (C13) which is the most potent antagonist reported to date with an IC50 of 36 mu M. The molecules described in this manuscript are anticipated to serve as valuable tools in the study of quorum sensing in Vibrio cholerae and provide new leads in the development of an antivirulence therapy against this human pathogen. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.09.021
• 作为产物：
  描述：

  S-2-羟基丁酸 、 叔丁基二甲基氯硅烷 在 咪唑 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 8.0h， 生成 (2S)-2-[[(1,1-Dimethylethyl)dimethylsilyl]oxy]butanoic acid
  参考文献：
  名称：

  Small molecule probes of the receptor binding site in the Vibrio cholerae CAI-1 quorum sensing circuit

  摘要：

  Based on modification of separate structural features of the Vibrio cholerae quorum sensing signal, (S)-3-hydroxytridecan-4-one (CAI-1), three focused compound libraries have been synthesized and evaluated for biological activity. Modifications to the acyl tail and alpha-hydroxy ketone typically provided agonists with activities correlated to tail length and conservative changes to the hydroxy ketone. Among the molecules identified within this collection of agonists is Am-CAI-1 (B11), which is among the most potent agonists reported to date with an EC50 of 0.21 mu M. Modifications to the ethyl side chain delivered molecules with both agonist and antagonist activity, including m-OH-Ph-CAI-1 (C13) which is the most potent antagonist reported to date with an IC50 of 36 mu M. The molecules described in this manuscript are anticipated to serve as valuable tools in the study of quorum sensing in Vibrio cholerae and provide new leads in the development of an antivirulence therapy against this human pathogen. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.09.021

文献信息

• Role of the CAI-1 Fatty Acid Tail in the <i>Vibrio cholerae</i> Quorum Sensing Response
  作者：Lark J. Perez、Wai-Leung Ng、Paul Marano、Karolina Brook、Bonnie L. Bassler、Martin F. Semmelhack

  DOI：10.1021/jm300908t

  日期：2012.11.26

  Quorum sensing is a mechanism of chemical communication among bacteria that enables collective behaviors. In V. cholerae, the etiological agent of the disease cholera, quorum sensing controls group behaviors including virulence factor production and biofilm formation. The major V. cholerae quorum-sensing system consists of the extracellular signal molecule called CAI-1 and its cognate membrane bound receptor called CqsS. Here, the ligand binding activity of CqsS is probed with structural analogues of the natural signal. Enabled by our discovery of a structurally simplified analogue of CAI-1, we prepared and analyzed a focused library. The molecules were designed to probe the effects of conformational and structural changes along the length of the fatty acid tail of CAI-1. Our results, combined with pharmacophore modeling, suggest a molecular basis for signal molecule recognition and receptor fidelity with respect to the fatty acid tail portion of CAI-1. These efforts provide novel probes to enhance discovery of antivirulence agents for the treatment of V. cholerae.