resolvin E1(1-)

• 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: resolvin E1(1-)
• 英文别名: (5S,6Z,8E,10E,12R,14Z,16E,18R)-5,12,18-trihydroxyicosa-6,8,10,14,16-pentaenoate
• 化学式: C₈H₇N₂O₃Pol
• 分子量: 349.4
• InChiKey: AOPOCGPBAIARAV-OTBJXLELSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  25
• 可旋转键数：
  12
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  101
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  resolvin E1(1-) 在 tin(ll) chloride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 [(2S,3S,3aS,6R,6aR)-3-hydroxy-2-[[1-[[4-(4-methylphenyl)sulfonyloxyphenyl]methyl]triazol-4-yl]methoxy]-5-oxo-3,3a,6,6a-tetrahydro-2H-furo[3,2-b]furan-6-yl] benzoate
  参考文献：
  名称：

  2,3,4,5-四氢-1 H-苯并[ e ] [1,4]二氮杂pine衍生物的固相合成

  摘要：

  我们已经开发出一种有效的固相合成方法，用于合成2,3,4,5-四氢-1 H-苯并[ e ] [1,4]二氮杂pine衍生物。该方法对于这些潜在的生物活性分子的高通量合成是有价值的。

  DOI：

  10.1016/j.tetlet.2011.05.138
• 作为产物：
  描述：

  aminomethyl-terminated Tentagel resin 、 邻硝基苯甲酸 在 1-羟基苯并三唑 、 N,N'-二异丙基碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 resolvin E1(1-)
  参考文献：
  名称：

  2,3,4,5-四氢-1 H-苯并[ e ] [1,4]二氮杂pine衍生物的固相合成

  摘要：

  我们已经开发出一种有效的固相合成方法，用于合成2,3,4,5-四氢-1 H-苯并[ e ] [1,4]二氮杂pine衍生物。该方法对于这些潜在的生物活性分子的高通量合成是有价值的。

  DOI：

  10.1016/j.tetlet.2011.05.138

文献信息

• Metabolic Inactivation of Resolvin E1 and Stabilization of Its Anti-inflammatory Actions
  作者：Makoto Arita、Sungwhan F. Oh、Tomomichi Chonan、Song Hong、Siva Elangovan、Yee-Ping Sun、Jasim Uddin、Nicos A. Petasis、Charles N. Serhan

  DOI：10.1074/jbc.m603766200

  日期：2006.8

  metabolic inactivation and proved to retain biological activity reducing PMN infiltration and pro-inflammatory cytokine/chemokine production in vivo. These results established the structure of a novel RvE1 initial metabolite, indicating that conversion of RvE1 to the oxo product represents a mode of RvE1 inactivation. Moreover, the designed RvE1 analog, which resisted further metabolism/inactivation, could

  Resolvins（Rv）是源自omega-3多不饱和脂肪酸的脂质介体，在局部炎症环境中起作用，以阻止白细胞募集并促进分解。Resolvin E1（RvE1;（5S，12R，18R）-三羟基-6Z，8E，10E，14Z，16E-二十碳五烯酸）是一种衍生自omega-3二十碳五烯酸的加氧酶产品，具有强大的抗炎/消炎作用。体内。在这里，我们确定氧化还原酶是否催化RvE1的转化并评估RvE1代谢产物的生物学活性。以NAD +作为辅因子，重组15-羟基前列腺素脱氢酶充当18-羟基脱氢酶，形成18-氧代-RvE1。在鼠肺中，碳18位上的羟基脱氢形成18-oxo-RvE1是RvE1的主要初始代谢途径。RvE1在酵母聚糖诱导的腹膜炎中有效减少多形核白细胞（PMN）募集的浓度下，18-oxo-RvE1没有活性。在人类嗜中性粒细胞中，RvE1的碳20羟基化是主要的转化途径。合成了一种RvE1类似物，即19-
• Solid-phase synthesis of N-substituted 3,4-dihydroquinazolinone derivatives
  作者：Zhang Liu、Lili Ou、Marc A. Giulianotti、Richard A. Houghten

  DOI：10.1016/j.tetlet.2011.03.034

  日期：2011.5

  An efficient solid-phase synthetic approach for the synthesis of N-substituted 3, 4-dihydroquinazolinone derivatives has been developed. Four different 2-nitrobenzoic acids and three different 2-phenylacetyl chlorides were employed in the synthesis of this library. After purification, all products were obtained in good yields. (C) 2011 Elsevier Ltd. All rights reserved.
• Pro-resolving actions and stereoselective biosynthesis of 18S E-series resolvins in human leukocytes and murine inflammation
  作者：Sungwhan F. Oh、Padmini S. Pillai、Antonio Recchiuti、Rong Yang、Charles N. Serhan

  DOI：10.1172/jci42545

  日期：2011.2.1

  E-series resolvins are antiinflammatory and pro-resolving lipid mediators derived from the omega-3 polyunsaturated fatty acid eicosapentaenoic acid (EPA) that actively clear inflammation to promote tissue homeostasis. Aspirin, in addition to exerting antithrombotic actions, also triggers the biosynthesis of these specialized pro-resolving mediators. Here, we used metabolomic profiling to investigate the biosynthesis of E-series resolvins with specific chiral chemistry in serum from human subjects and present evidence for new 18S series resolvins. Aspirin increased endogenous formation of 18S-hydroxyeicosapentaenoate (18S-HEPE) compared with 18R-HEPE, a known resolvin precursor. Human recombinant 5-lipoxygenase used both enantiomers as substrates, and recombinant LTA(4) hydrolase (LTA4H) converted chiral 5S(6)-epoxide-containing intermediates to resolvin El and 18S-resolvin El (RvE1 and 18S-RvE1, respectively). 18S-RvE1 bound to the leukocyte GPCRs ChemR23 and BLT1 with increased affinity and potency compared with the R-epimer, but was more rapidly inactivated than RvE1 by dehydrogenase. Like RvE1, 18S-RvE1 enhanced macrophage phagocytosis of zymosan, E. coli, and apoptotic neutrophils and reduced both neutrophil infiltration and proinflammatory cytokines in murine peritonitis. These results demonstrate two parallel stereospecific pathways in the biosynthesis of E-series resolvins, 18R- and 18S-, which are antiinflammatory, pro-resolving, and non-phlogistic and may contribute to the beneficial actions of aspirin and omega-3 polyunsaturated fatty acids.
• Resolvin E2: Identification and Anti-Inflammatory Actions: Pivotal Role of Human 5-Lipoxygenase in Resolvin E Series Biosynthesis
  作者：Eric Tjonahen、Sungwhan F. Oh、Jeffrey Siegelman、Siva Elangovan、Katherine B. Percarpio、Song Hong、Makoto Arita、Charles N. Serhan

  DOI：10.1016/j.chembiol.2006.09.011

  日期：2006.11

  The family of resolvins consists of omega-3 fatty acid-derived mediators, including E series resolvins generated from eicosapentaenoic acid (EPA), and carry potent anti-inflammatory properties. Here, we report the isolation, identification, and bioactions of resolvin E2 (RvE2), which is 5S,18-dihydroxy-eicosapentaenoic acid. RvE2 stopped zymosan-induced polymorphonuclear (PMN) leukocyte infiltration and displayed potent anti-inflammatory properties in murine peritonitis. We also demonstrate that human recombinant 5-lipoxygenase generates RvE2 from a common precursor of E series resolvins, namely, 18-hydroxyeicosapentaenoate (18-HEPE). Furthermore, the initial 5-hydroperoxide intermediate was also converted to a 5(6)-epoxide intermediate in RvE1 formation. These results demonstrate that RvE2, together with RvE1, may contribute to the beneficial actions of omega-3 fatty acids in human diseases. Moreover, they indicate that the 5-lipoxygenase in human leukocytes is a pivotal enzyme that can produce both pro- and anti-inflammatory chemical mediators.