4-((2R,3R)-3-((E)-((2R,3R)-3-hydroxy-2-((Z)-oct-2-en-1-yl)-5-oxocyclopentylidene)methyl)oxiran-2-yl)butanoic acid

• 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: 4-((2R,3R)-3-((E)-((2R,3R)-3-hydroxy-2-((Z)-oct-2-en-1-yl)-5-oxocyclopentylidene)methyl)oxiran-2-yl)butanoic acid
• 英文别名: 4-[(2R,3R)-3-(((E)-(2R,3R)-3-hydroxy-2-((Z)-oct-2-enyl)-5-oxocyclopentylidene)methyl)oxiran-2-yl]butanoic acid；4-[(2R,3R)-3-((E)-((2R,3R)-3-hydroxy-2-((Z)-oct-2-enyl)-5-oxocyclopentylidene)methyl)oxiran-2-yl]butanoic acid；(2R,3R)-3-Z-[(4R,5R)-4-hydroxy-5-(2Z-octenyl)-2-oxo-cyclopentylidenemethyl]oxirane-2-butanoic acid；EI；4-[(2R,3R)-3-[(E)-[(2R,3R)-3-hydroxy-2-[(Z)-oct-2-enyl]-5-oxocyclopentylidene]methyl]oxiran-2-yl]butanoic acid
• 化学式: C₂₀H₃₀O₅
• 分子量: 350.455
• InChiKey: HHCKGRLRYHXQJS-QRKAMBPMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  25
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  87.1
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  (1S,4R)-1-acetyloxy-4-(4-methoxyphenylmethoxy)cyclopent-2-ene 在 sodium chlorite 、 甲酸 、 sodium dihydrogenphosphate dihydrate 、 溴 、 叔丁基锂 、 sodium hexamethyldisilazane 、 四氯化钛 、 二异丁基氢化铝 、 碳酸氢钠 、 potassium carbonate 、 戴斯-马丁氧化剂 、 pyridinium chlorochromate 、 2,3-二氯-5,6-二氰基-1,4-苯醌 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 、 二氯甲烷 、 水 、 叔丁醇 、 正戊烷 为溶剂， 反应 12.83h， 生成 4-((2R,3R)-3-((E)-((2R,3R)-3-hydroxy-2-((Z)-oct-2-en-1-yl)-5-oxocyclopentylidene)methyl)oxiran-2-yl)butanoic acid
  参考文献：
  名称：

  An Epoxyisoprostane Is a Major Regulator of Endothelial Cell Function

  摘要：

  The goal of these studies was to determine the effect of 5,6-epoxyisoprostane, El, on human aortic endothelial cells (HAEC). El can form as a phospholipase product of 1-palmitoyl-2-(5,6-epoxyisoprostane E2)-sn-glycero-3-phosphocholine, PEIPC, a proinflammatory molecule that accumulates in sites of inflammation where phospholipases are also increased. To determine the effect of El on HAEC, we synthesized several stereoisomers of El using a convergent approach from the individual optically pure building blocks, the epoxyaldehydes 5 and 6 and the bromoenones 14 and 16. The desired stereoisomer of El can be prepared from these materials in only six operations, and thus, large amounts of the product can be obtained. The trans/trans isomers had the most potent activity, suggesting specificity in the interaction of El with the cell surface. El has potent anti-inflammatory effects in HAEC. El strongly inhibits the production of MCP-1, a major monocyte chemotactic factor, and either decreases or minimally increases the levels of 10 proinflammatory molecules increased by PEIPC. El also strongly down-regulates the inflammatory effects of IL-1 beta, a major inflammatory cytokine. Thus El, a hydrolytic product of PEIPC, has potent anti-inflammatory function.

  DOI：

  10.1021/jm400959q

文献信息

• Synthesis of Epoxyisoprostanes: Effects in Reducing Secretion of Pro-inflammatory Cytokines IL-6 and IL-12
  作者：Julian Egger、Peter Bretscher、Stefan Freigang、Manfred Kopf、Erick M. Carreira

  DOI：10.1002/anie.201300739

  日期：2013.5.10

  chemoselective steps, including a CH insertion for the rapid construction of the cyclopentanone ring. The synthesized compounds display unprecedented biological activity in reducing the secretion of pro‐inflammatory cytokines.

  抗炎：以难以捉摸epoxyisoprostanoid高效而通用合成途径，磷脂PECPC和PEIPC，随着isoprostanoids EC和EI，依赖于许多的立体和化学选择性的步骤，包括一个C  ħ插入供的快速施工环戊酮环。合成的化合物在减少促炎性细胞因子的分泌方面显示出前所未有的生物学活性。
• Total Synthesis of the Epoxy Isoprostane Phospholipids PEIPC and PECPC
  作者：Michael E. Jung、Judith A. Berliner、Daniela Angst、Dawei Yue、Lukasz Koroniak、Andrew D. Watson、Rongsong Li

  DOI：10.1021/ol051415y

  日期：2005.9.1

  A total synthesis of the naturally occurring hydroxy ketone PEIPC 1, a compound that plays a role in endothelial activation in atherosclerosis, has been completed via a triply convergent preparation of a protected El derivative 13 from 3,5-diacetoxycyclopentene 7, pentane-1,5-diol, and vinyllithium, using Sharpless epoxidation and enzymatic resolution as key steps. Final coupling with lyso-PC 16 and silyl group deprotection gave PECK 2 and PEIPC 1, which showed the same activity as natural PECPC and PEIPC.
• Improved Synthesis of the Epoxy Isoprostane Phospholipid PEIPC and its Reactivity with Amines
  作者：Michael E. Jung、Judith A. Berliner、Lukasz Koroniak、B. Gabriel Gugiu、Andrew D. Watson

  DOI：10.1021/ol8014804

  日期：2008.10.2

  An improved synthesis of the naturally occurring hydroxy ketone 1-palmitoyl-2-(5,6)-epoxyisoprostane E-2-sn-glycero-3-phosphocholine (PEIPC) 1, a compound that plays a role in endothelial activation in atherosclerosis, has been carried out using a PMB ether as the key protecting group. Opening of an intermediate with pentylamine shows that the allylic epoxide is the position of attack by nucleophiles.
• An Epoxyisoprostane Is a Major Regulator of Endothelial Cell Function
  作者：Wei Zhong、James R. Springstead、Ramea Al-Mubarak、Sangderk Lee、Rongsong Li、Benjamin Emert、Judith A. Berliner、Michael E. Jung

  DOI：10.1021/jm400959q

  日期：2013.11.14

  The goal of these studies was to determine the effect of 5,6-epoxyisoprostane, El, on human aortic endothelial cells (HAEC). El can form as a phospholipase product of 1-palmitoyl-2-(5,6-epoxyisoprostane E2)-sn-glycero-3-phosphocholine, PEIPC, a proinflammatory molecule that accumulates in sites of inflammation where phospholipases are also increased. To determine the effect of El on HAEC, we synthesized several stereoisomers of El using a convergent approach from the individual optically pure building blocks, the epoxyaldehydes 5 and 6 and the bromoenones 14 and 16. The desired stereoisomer of El can be prepared from these materials in only six operations, and thus, large amounts of the product can be obtained. The trans/trans isomers had the most potent activity, suggesting specificity in the interaction of El with the cell surface. El has potent anti-inflammatory effects in HAEC. El strongly inhibits the production of MCP-1, a major monocyte chemotactic factor, and either decreases or minimally increases the levels of 10 proinflammatory molecules increased by PEIPC. El also strongly down-regulates the inflammatory effects of IL-1 beta, a major inflammatory cytokine. Thus El, a hydrolytic product of PEIPC, has potent anti-inflammatory function.