6-(1,3-dioxan-2-yl)-4-oxohexanoic acid | 1200436-66-3

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 酮酸及其衍生物
• 英文名称: 6-(1,3-dioxan-2-yl)-4-oxohexanoic acid
• 英文别名: 6-(1,3-Dioxan-2-yl)-4-oxohexanoic acid
• CAS: 1200436-66-3
• 化学式: C₁₀H₁₆O₅
• 分子量: 216.234
• InChiKey: IUAPBCDGMGIVPY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.3
• 重原子数：
  15
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  72.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  6-(1,3-dioxan-2-yl)-4-oxohexanoic acid 在 溶剂黄146 作用下， 以 水 为溶剂， 生成 4,7-dioxo-heptanoic acid
  参考文献：
  名称：

  Efficient Quantitative Analysis of Carboxyalkylpyrrole Ethanolamine Phospholipids: Elevated Levels in Sickle Cell Disease Blood

  摘要：

  γ-羟基-α、β-不饱和醛类是由多不饱和磷脂氧化破坏产生的，形成了含有乙醇胺磷脂（EP）氨基的吡咯衍生物，如 2-戊基吡咯（PP）-EP 和 2-(ω-羧基烷基)吡咯（CAP）-EP 衍生物：2-(ω-羧乙基)吡咯（CEP）-EP、2-(ω-羧丙基)吡咯（CPP）-EP 和 2-(ω-羧庚基)吡咯（CHP）-EP。由于 EPs 在体内以各种形式存在，因此预计会产生分子量不同的吡咯修饰 EPs 的复杂混合物。为了提供一个灵敏的氧化应激指数，用磷脂酶 D 处理每种混合物，释放出单个 CAP-乙醇胺（ETN）或 PP-ETN，从而消除与甘油磷脂分子有关的所有质量差异。通过 LC-MS/MS 分析了镰状细胞病（SCD）患者总血液磷脂的磷脂分解产物混合物。该方法被用于检测镰状细胞病（SCD）患者临床监测血浆中 CAP-EP 和 PP-EP 的水平。我们发现，血液中的 CEP-EP 水平普遍升高（63.9 ± 9.7 nM），与老年性黄斑变性（AMD）患者血液中的平均水平（56.3 ± 37.1 nM）相似；在住院治疗镰状细胞危象的 SCD 患者血浆中检测到的 CEP-EP 水平低 2 倍（27.6 ± 3.6 nM，n = 5），但平均水平仍高于健康对照组血液中检测到的水平（12.1 ± 10.5 nM）。SCD门诊患者血浆中的CPP-EP水平比住院治疗镰状细胞危象的SCD患者高4倍（45.1 ± 10.9 nM，n = 5对10.9 ± 3.4 nM，n = 6；P < 0.002）。SCD门诊患者血浆中的PP-EP浓度比住院治疗镰状细胞危象的SCD患者血浆样本中的PP-EP浓度高出近4.8倍（7.06 ± 4.05 vs 1.48 ± 0.92 nM；p < 0.05）。由于 CAP-EPs 可促进血管生成和血小板活化，因此 SCD 血液中的 CAP-EPs 水平升高可导致高凝状态和血管闭塞事件，而这正是 SCD 的关键病理生理特征。

  DOI：

  10.1021/acs.chemrestox.6b00152
• 作为产物：
  描述：

  6-[1,3]dioxan-2-yl-4-oxo-hexanoic acid methyl ester 在 水 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 3.0h， 生成 6-(1,3-dioxan-2-yl)-4-oxohexanoic acid
  参考文献：
  名称：

  Synthesis and structural characterization of carboxyethylpyrrole-modified proteins: mediators of age-related macular degeneration

  摘要：

  Protein modifications in which the e-amino group of lysyl residues is incorporated into a 2-(omega-carboxy-ethyl)pyrrole (CEP) are mediators of age-related macular degeneration (AMD). They promote both angiogenesis into the retina ('wet AMD') and geographic retinal atrophy ('dry AMD'). Blood levels of CEPs are biomarkers for clinical prognosis of the disease. To enable mechanistic studies of their role in promoting AMD, for example, through the activation of B- and T-cells, interaction with receptors, or binding with complement proteins, we developed an efficient synthesis of CEP derivatives, that is especially effective for proteins. The structures of tryptic peptides derived from CEP-modified proteins were also determined. A key finding is that 4,7-dioxoheptanoic acid 9-fluorenylmethyl ester reacts with primary amines to provide 9-fluorenylmethyl esters of CEP-modified proteins that can be deprotected in situ with 1,8-diazabicyclo[5.4.0]undec-7-ene without causing protein denaturation. The introduction of multiple CEP-modifications with a wide variety of CEP: protein ratios is readily achieved using this strategy. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.09.009

文献信息

• DETECTION OF CARBOXYALKYLPYRROLE OR PENTYLPYRROLE ETHANOLAMINE PHOSPHOLIPIDS
  申请人：CASE WESTERN RESERVE UNIVERSITY

  公开号：US20170176470A1

  公开（公告）日：2017-06-22

  A method of detecting carboxyalkylpyrrole ethanolamine phospholipids (CAP-EPs) or pentylpyrrole ethanolamine phospholipids (CAP-EPs) in a bodily sample from a subject includes obtaining a bodily sample from a subject suspected of including carboxyalkylpyrrole ethanolamine phospholipids (CAP-EPs) or pentylpyrrole ethanolamine phospholipids (PP-EPs) extracting carboxyalkylpyrrole ethanolamine phospholipids or pentylpyrrole ethanolamine phospholipids from the bodily sample; hydrolyzing carboxyalkylpyrrole or pentylpyrrole ethanolamine phospholipids from the extracted with a phospholipase D to form carboxyalkylpyrrole ethanolamine (CAP-ETN) and pentylpyrrole ethanolamine (PP-ETN) derivatives; and determining the amount of carboxyalkylpyrrole ethanolamine (CAP-ETN) and pentylpyrrole ethanolamine (PP-ETN) by mass spectrometry.
• Synthesis and structural characterization of carboxyethylpyrrole-modified proteins: mediators of age-related macular degeneration
  作者：Liang Lu、Xiaorong Gu、Li Hong、James Laird、Keeve Jaffe、Jaewoo Choi、John Crabb、Robert G. Salomon

  DOI：10.1016/j.bmc.2009.09.009

  日期：2009.11

  Protein modifications in which the e-amino group of lysyl residues is incorporated into a 2-(omega-carboxy-ethyl)pyrrole (CEP) are mediators of age-related macular degeneration (AMD). They promote both angiogenesis into the retina ('wet AMD') and geographic retinal atrophy ('dry AMD'). Blood levels of CEPs are biomarkers for clinical prognosis of the disease. To enable mechanistic studies of their role in promoting AMD, for example, through the activation of B- and T-cells, interaction with receptors, or binding with complement proteins, we developed an efficient synthesis of CEP derivatives, that is especially effective for proteins. The structures of tryptic peptides derived from CEP-modified proteins were also determined. A key finding is that 4,7-dioxoheptanoic acid 9-fluorenylmethyl ester reacts with primary amines to provide 9-fluorenylmethyl esters of CEP-modified proteins that can be deprotected in situ with 1,8-diazabicyclo[5.4.0]undec-7-ene without causing protein denaturation. The introduction of multiple CEP-modifications with a wide variety of CEP: protein ratios is readily achieved using this strategy. (C) 2009 Elsevier Ltd. All rights reserved.
• Efficient Quantitative Analysis of Carboxyalkylpyrrole Ethanolamine Phospholipids: Elevated Levels in Sickle Cell Disease Blood
  作者：Junhong Guo、Hua Wang、Borys Hrinczenko、Robert G. Salomon

  DOI：10.1021/acs.chemrestox.6b00152

  日期：2016.7.18

  γ-Hydroxy-α,β-unsaturated aldehydes, generated by oxidative damage of polyunsaturated phospholipids, form pyrrole derivatives that incorporate the ethanolamine phospholipid (EP) amino group such as 2-pentylpyrrole (PP)-EP and 2-(ω-carboxyalkyl)pyrrole (CAP)-EP derivatives: 2-(ω-carboxyethyl)pyrrole (CEP)-EP, 2-(ω-carboxypropyl)pyrrole (CPP)-EP, and 2-(ω-carboxyheptyl)pyrrole (CHP)-EP. Because EPs occur in vivo in various forms, a complex mixture of pyrrole-modified EPs with different molecular weights is expected to be generated. To provide a sensitive index of oxidative stress, all of the differences in mass related to the glycerophospholipid moieties were removed by releasing a single CAP-ethanolamine (ETN) or PP-ETN from each mixture by treatment with phospholipase D. Accurate quantization was achieved using the corresponding ethanolamine-d4 pyrroles as internal standards. The product mixture obtained by phospholipolysis of total blood phospholipids from sickle cell disease (SCD) patients was analyzed by LC-MS/MS. The method was applied to measure CAP-EP and PP-EP levels in blood plasma from clinical monitoring of SCD patients. We found uniformly elevated blood levels of CEP-EP (63.9 ± 9.7 nM) similar to mean levels in blood from age-related macular degeneration (AMD) patients (56.3 ± 37.1 nM), and 2-fold lower levels (27.6 ± 3.6 nM, n = 5) were detected in plasma from SCD patients hospitalized to treat a sickle cell crisis, although mean levels remain higher than those (12.1 ± 10.5 nM) detected in blood from healthy controls. Plasma levels of CPP-EPs from SCD clinic patients were 4-fold higher than those of SCD patients hospitalized to treat a sickle cell crisis (45.1 ± 10.9 nM, n = 5 versus 10.9 ± 3.4 nM, n = 6; p < 0.002). PP-EP concentration in plasma from SCD clinic patients is nearly 4.8-fold higher than its level in plasma samples from SCD patients hospitalized to treat a sickle cell crisis (7.06 ± 4.05 vs 1.48 ± 0.92 nM; p < 0.05). Because CAP-EPs promote angiogenesis and platelet activation, the elevated levels present in SCD blood can contribute to the hypercoaguability and vaso-occlusive events that are critical pathophysiologic features of SCD.

  γ-羟基-α、β-不饱和醛类是由多不饱和磷脂氧化破坏产生的，形成了含有乙醇胺磷脂（EP）氨基的吡咯衍生物，如 2-戊基吡咯（PP）-EP 和 2-(ω-羧基烷基)吡咯（CAP）-EP 衍生物：2-(ω-羧乙基)吡咯（CEP）-EP、2-(ω-羧丙基)吡咯（CPP）-EP 和 2-(ω-羧庚基)吡咯（CHP）-EP。由于 EPs 在体内以各种形式存在，因此预计会产生分子量不同的吡咯修饰 EPs 的复杂混合物。为了提供一个灵敏的氧化应激指数，用磷脂酶 D 处理每种混合物，释放出单个 CAP-乙醇胺（ETN）或 PP-ETN，从而消除与甘油磷脂分子有关的所有质量差异。通过 LC-MS/MS 分析了镰状细胞病（SCD）患者总血液磷脂的磷脂分解产物混合物。该方法被用于检测镰状细胞病（SCD）患者临床监测血浆中 CAP-EP 和 PP-EP 的水平。我们发现，血液中的 CEP-EP 水平普遍升高（63.9 ± 9.7 nM），与老年性黄斑变性（AMD）患者血液中的平均水平（56.3 ± 37.1 nM）相似；在住院治疗镰状细胞危象的 SCD 患者血浆中检测到的 CEP-EP 水平低 2 倍（27.6 ± 3.6 nM，n = 5），但平均水平仍高于健康对照组血液中检测到的水平（12.1 ± 10.5 nM）。SCD门诊患者血浆中的CPP-EP水平比住院治疗镰状细胞危象的SCD患者高4倍（45.1 ± 10.9 nM，n = 5对10.9 ± 3.4 nM，n = 6；P < 0.002）。SCD门诊患者血浆中的PP-EP浓度比住院治疗镰状细胞危象的SCD患者血浆样本中的PP-EP浓度高出近4.8倍（7.06 ± 4.05 vs 1.48 ± 0.92 nM；p < 0.05）。由于 CAP-EPs 可促进血管生成和血小板活化，因此 SCD 血液中的 CAP-EPs 水平升高可导致高凝状态和血管闭塞事件，而这正是 SCD 的关键病理生理特征。