1-(2S)-1,4-二氧杂螺[4.5]癸-2-基-1,2-丙二酮 | 848035-01-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 1-(2S)-1,4-二氧杂螺[4.5]癸-2-基-1,2-丙二酮
• 英文名称: (S)-4,5-cyclohexylidenedioxy-2,3-pentanedione
• 英文别名: (S)-4,5-cyclohexylidenedioxy-2,3-pentadione；1-[(3S)-1,4-dioxaspiro[4.5]decan-3-yl]propane-1,2-dione
• CAS: 848035-01-8
• 化学式: C₁₁H₁₆O₄
• 分子量: 212.246
• InChiKey: OHQIVKZQGGEQDZ-VIFPVBQESA-N

物化性质

• 沸点：
  321.1±37.0 °C(Predicted)
• 密度：
  1.17±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  52.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-(2S)-1,4-二氧杂螺[4.5]癸-2-基-1,2-丙二酮 在 硫酸 、 重水 作用下， 反应 2.5h， 生成 6-甲基-2-硫代-2,3-二氢-4H-1,3-苯并噁嗪-4-酮
  参考文献：
  名称：

  [EN] EXPEDITIOUS SYNTHESIS OF DPD
  [FR] SYNTHESE RAPIDE DE DPD

  摘要：

  这项发明提供了一种实用的合成途径，用于合成4,5-二羟基戊烷-2,3-二酮（DPD），这是一种不稳定的小分子，被认为是细菌群体感应通用信号物质的来源。该合成途径包括新的中间体，并允许制备同位素标记的DPD和ent-DPD。该方法提供了足够数量的DPD，以研究硼酸与DPD的自发结合，这是海洋细菌V. harveyi的信号。

  公开号：

  WO2006034269A1
• 作为产物：
  描述：

  5-((2S)-1,4-dioxaspiro[4.5]dec-2-yl)(3S,4R,5S)-3,4-dihydroxy-3,4,5-trihydrofuran-2-one 在 ruthenium(IV) oxide sodium periodate 、 potassium metaperiodate 、 水 、 potassium hydrogencarbonate 、 三苯基膦 作用下， 以 四氢呋喃 、 四氯化碳 、 正己烷 、 二氯甲烷 、 水 、 乙腈 为溶剂， 反应 24.75h， 生成 1-(2S)-1,4-二氧杂螺[4.5]癸-2-基-1,2-丙二酮
  参考文献：
  名称：

  An Expeditious Synthesis of DPD and Boron Binding Studies

  摘要：

  A practical synthesis has been developed for DPD (4,5-dihydroxypentane-2,3-dione), an unstable small molecule that is proposed to be the source of universal signaling agents for quorum sensing in bacteria. The synthesis allows preparation of isotopically labeled DPD and entDPD as well as detailed studies of spontaneous binding to borate to give the unusual borate complex 6, the signal for marine bacteria such as Vibrio harveyi.

  DOI：

  10.1021/ol047695j

文献信息

• [EN] EXPEDITIOUS SYNTHESIS OF DPD<br/>[FR] SYNTHESE RAPIDE DE DPD
  申请人：UNIV PRINCETON

  公开号：WO2006034269A1

  公开（公告）日：2006-03-30

  This invention provides a practical synthesis route for 4,5-dihydroxypentane-2,3-dione (DPD), an unstable small molecule which is proposed to be the source of universal signaling agents for quorum sensing in bacteria. The synthesis route includes new intermediates and allows preparation of isotopically-labeled DPD and ent-DPD. The method provides sufficient quantities of DPD for study of spontaneous binding of borate to DPD, the signal for the marine bacteria V. harveyi

  这项发明提供了一种实用的合成途径，用于合成4,5-二羟基戊烷-2,3-二酮（DPD），这是一种不稳定的小分子，被认为是细菌群体感应通用信号物质的来源。该合成途径包括新的中间体，并允许制备同位素标记的DPD和ent-DPD。该方法提供了足够数量的DPD，以研究硼酸与DPD的自发结合，这是海洋细菌V. harveyi的信号。
• An Unexpected Switch in the Modulation of AI-2-Based Quorum Sensing Discovered through Synthetic 4,5-Dihydroxy-2,3-pentanedione Analogues
  作者：Colin A. Lowery、Junguk Park、Gunnar F. Kaufmann、Kim D. Janda

  DOI：10.1021/ja802353j

  日期：2008.7.1

  Quorum sensing (QS) has traditionally referred to a mechanism of communication within a species of bacteria. However, emerging research implicates QS in interspecies communication and competition, and such systems have been proposed in a wide variety of bacteria, The AI-2-based QS system represents the most studied of these proposed interspecies systems, and has been proposed to regulate diverse functions such as bioluminescence, expression of virulence factors, and biofilm formation. As such, the development of modulatory compounds, both agonists and antagonists, is of great interest for the treatment of bacterial infections and the study of unknown AI-2-based QS systems. Toward this end, we have designed and synthesized a panel of 4,5-dihydroxy-2,3-pentanedione/AI-2 analogues and evaluated their effects on the AI-2 QS of various bacteria. The panel of compounds exhibited differential effects in the bacterial cell lines examined, providing a platform for the development of broad-spectrum modulators of AI-2-based QS.
• Inhibition of Pseudomonas aeruginosa quorum sensing by AI-2 analogs
  作者：Hadas Ganin、Xu Tang、Michael M. Meijler

  DOI：10.1016/j.bmcl.2009.03.163

  日期：2009.7

  Autoinducer-2 (AI-2) has been suggested to serve as a universal interspecies quorum sensing signaling molecule. We have synthesized a set of AI-2 analogs with small incremental changes in alkyl substitution on C-2 and evaluated them for their agonistic and antagonistic potential as quorum sensing (QS) attenuators in two different bacterial species: Pseudomonas aeruginosa and Vibrio harveyi. Unexpectedly, several of the analogs were found to function as synergistic QS agonists in V. harveyi, while two of these analogs inhibit QS in P. aeruginosa. (C) 2009 Elsevier Ltd. All rights reserved.
• Pyrogallol and its analogs can antagonize bacterial quorum sensing in Vibrio harveyi
  作者：Nanting Ni、Gaurav Choudhary、Minyong Li、Binghe Wang

  DOI：10.1016/j.bmcl.2008.01.081

  日期：2008.3

  Bacteria can coordinate community-wide behaviors through quorum sensing, that is, the secretion and sensing of autoinducer (AI) molecules. Bacterial quorum sensing is implicated in the regulation of pathologically relevant events such as biofilm formation, bacterial virulence, and drug resistance. Inhibitors of bacterial quorum sensing could therefore be useful therapeutics. Herein we report for the first time the discovery of several pyrogallol compounds as single digit micromolar inhibitors of bacterial quorum sensing in Vibrio harveyi. (c) 2008 Elsevier Ltd. All rights reserved.
• Processing the Interspecies Quorum-sensing Signal Autoinducer-2 (AI-2)
  作者：João C. Marques、Pedro Lamosa、Caitlin Russell、Rita Ventura、Christopher Maycock、Martin F. Semmelhack、Stephen T. Miller、Karina B. Xavier

  DOI：10.1074/jbc.m111.230227

  日期：2011.5

  The molecule (S)-4,5-dihydroxy-2,3-pentanedione (DPD) is produced by many different species of bacteria and is the precursor of the signal molecule autoinducer-2 (AI-2). AI-2 mediates interspecies communication and facilitates regulation of bacterial behaviors such as biofilm formation and virulence. A variety of bacterial species have the ability to sequester and process the AI-2 present in their environment, thereby interfering with the cell-cell communication of other bacteria. This process involves the AI-2-regulated lsr operon, comprised of the Lsr transport system that facilitates uptake of the signal, a kinase that phosphorylates the signal to phospho-DPD (P-DPD), and enzymes (like LsrG) that are responsible for processing the phosphorylated signal. Because P-DPD is the intracellular inducer of the lsr operon, enzymes involved in P-DPD processing impact the levels of Lsr expression. Here we show that LsrG catalyzes isomerization of P-DPD into 3,4,4-trihydroxy-2-pentanone-5-phosphate. We present the crystal structure of LsrG, identify potential catalytic residues, and determine which of these residues affects P-DPD processing in vivo and in vitro. We also show that an lsrG deletion mutant accumulates at least 10 times more P-DPD than wild type cells. Consistent with this result, we find that the lsrG mutant has increased expression of the lsr operon and an altered profile of AI-2 accumulation and removal. Understanding of the biochemical mechanisms employed by bacteria to quench signaling of other species can be of great utility in the development of therapies to control bacterial behavior.