N-[(2S,3R,4R,5S,6R)-2,4,5,6,7-pentahydroxy-1-(6-oxo-5H-[1,3]dioxolo[4,5-g]quinoxalin-7-yl)heptan-3-yl]acetamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: N-[(2S,3R,4R,5S,6R)-2,4,5,6,7-pentahydroxy-1-(6-oxo-5H-[1,3]dioxolo[4,5-g]quinoxalin-7-yl)heptan-3-yl]acetamide
• 化学式: C₁₈H₂₃N₃O₉
• 分子量: 425.395
• InChiKey: IADCFOGCYPRNKT-IUNOTWKLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -3.3
• 重原子数：
  30
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  190
• 氢给体数：
  7
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  N-acetyl neuraminic acid 在 溶剂黄146 、 2-mercaptoethanol sodium salt 作用下， 反应 5.0h， 生成 N-[(2S,3R,4R,5S,6R)-2,4,5,6,7-pentahydroxy-1-(6-oxo-5H-[1,3]dioxolo[4,5-g]quinoxalin-7-yl)heptan-3-yl]acetamide
  参考文献：
  名称：

  Elevated concentrations of Neu5Ac and Neu5,9Ac2 in human plasma: potential biomarkers of cardiovascular disease

  摘要：

  摘要心血管疾病（CVD）是一组影响心脏和血管系统的健康问题，发病率和死亡率都非常高。心血管疾病的特征是高水平的炎症，而炎症与血浆中 N-乙酰神经氨酸（Neu5Ac）浓度的升高有关。尽管 Neu5Ac 是人体血浆中含量第二高的硅醛酸，但却没有针对心血管疾病研究过 Neu5,9Ac2。为了深入了解作为心血管疾病生物标记物的硅酸以及未来潜在的研究领域，我们设计了一项小规模试验研究，研究对象是 30 名确诊心血管疾病的患者以及 30 名年龄和性别匹配的健康对照者。每个样本都检测了 Neu5Ac 和 Neu5,9Ac2 的浓度。与健康对照组相比，心血管疾病患者的平均 Neu5Ac 和 Neu5,9Ac2 浓度明显升高（Neu5Ac：P < 0.001；Neu5,9Ac2：P < 0.04）。接收运算曲线（ROC）分析表明，Neu5Ac 和 Neu5,9Ac2 对心血管疾病都有合理的预测能力（Neu5Ac AUC：0.86；Neu5,9Ac2 AUC：0.71）。然而，Neu5Ac 的灵敏度（0.82）和特异性（0.81）都很好，而 Neu5,9Ac2 的特异性（0.81）相当，但灵敏度（0.44）很差。Neu5Ac + Neu5,9Ac2组合标记物的预测能力（AUC：0.93）、灵敏度（0.87）和特异性（0.90）均优于单独的Neu5Ac。与已知的炎症标记物高灵敏度 c 反应蛋白（hs-CRP：P 值：NS，ROC：0.50）进行比较后发现，Neu5Ac 和 Neu5,9Ac2 均优于该标记物。此外，还将 hs-CRP 值与三种不同的硅酸标记物相结合，以确定对 AUC 值的影响。每种组合的 AUC 值都略有提高，其中 Neu5Ac + Neu5,9Ac2 + hs-CRP 的 AUC 值最高，为 0.97。由此看来，Neu5Ac 作为心血管疾病的预测标志物具有很好的潜力，加入 Neu5,9Ac2 可提高预测能力，加入 hs-CRP 可进一步提高预测能力。

  DOI：

  10.1007/s10719-023-10138-3

文献信息

• Exploring the Potential of Norbornene-Modified Mannosamine Derivatives for Metabolic Glycoengineering
  作者：Anne-Katrin Späte、Jeremias E. G. A. Dold、Ellen Batroff、Verena F. Schart、Daniel E. Wieland、Oliver R. Baudendistel、Valentin Wittmann

  DOI：10.1002/cbic.201600197

  日期：2016.7.15

  Not as bulky as thought: Two new norbornene‐modified mannosamine derivatives were synthesized and applied for metabolic glycoengineering. The norbornene reporters reacted as planned on the cell surface, by inverse‐electron‐demand Diels–Alder cycloaddition. Derivatization with 1,2‐diamino‐4,5‐methylenedioxybenzene (DMB) confirmed that both derivatives are accepted by cells and incorporated as sialic

  并不像想象的那么庞大：合成了两种新的降冰片烯修饰的甘露糖胺衍生物，并将其用于代谢糖工程。降冰片烯报道分子通过反电子需求Diels-Alder环加成反应按计划在细胞表面发生了反应。用1,2-二氨基-4,5-亚甲基二氧基苯（DMB）衍生化证实这两种衍生物都被细胞接受并以唾液酸形式结合。
• Quantitative Standards of 4‐ <i>O</i> ‐Acetyl‐ and 9‐ <i>O</i> ‐Acetyl‐ <i>N</i> ‐Acetylneuraminic Acid for the Analysis of Plasma and Serum
  作者：Jack Cheeseman、Concepcion Badia、Rebecca I. Thomson、Gunter Kuhnle、Richard A. Gardner、Daniel I. R. Spencer、Helen M. I. Osborn

  DOI：10.1002/cbic.202100662

  日期：2022.3.4

  Synthesised acetylated derivatives of N-acetylneuraminic acid, Neu5,9Ac2 and Neu4,5Ac2, alongside commercially available Neu5Ac and Neu5Gc were utilised as standards for the quantitative analysis of these derivatives in plasma and serum samples. Multiple derivatives could be detected in one assay, which exhibited high specificity and low limits of detection and quantitation.

  N-乙酰神经氨酸、Neu5,9Ac 2和 Neu4,5Ac 2的合成乙酰化衍生物以及市售的 Neu5Ac 和 Neu5Gc 被用作血浆和血清样品中这些衍生物的定量分析的标准。可以在一次测定中检测多种衍生物，其表现出高特异性和低检测限和定量限。
• Quantifying the Efficiency of<i>N</i>-Phenyl-D-mannosamine to Metabolically Engineer Sialic Acid on Cancer Cell Surface
  作者：Zhifang Zhou、Guochao Liao、Sergejs Stepanovs、Zhongwu Guo

  DOI：10.1080/07328303.2014.933483

  日期：2014.10.13

  A convenient method was developed for the quantification of sialic acids expressed by cells and used to analyze the efficiency of N-phenylacetyl-D-mannosamine (ManNPhAc) to metabolically glycoengineer SKMEL-28 cancer cell. For this purpose, ManNPhAc-cultured cells were treated with 2M acetic acid to release sialic acids, and the products were treated with 1,2-diamino-4,5-methylenedioxybenzene to form the corresponding derivatives that had strong UV absorptions. The reaction mixture was then applied to HPLC-UV analysis to determine the amounts and the ratios of natural sialic acid and its unnatural analog. It was confirmed that after incubation with ManNPhAc SKMEL-28 cell was effectively glycoengineered to express a significant amount of unnatural sialic acid.
• Acid–base properties of the reaction product of sialic acid with fluorogenic reagent, 1,2-diamino-4,5-methylenedioxybenzene (DMB)
  作者：Shu-Ling Lin、Sadako Inoue、Yasuo Inoue

  DOI：10.1016/s0008-6215(00)00177-4

  日期：2000.11

  N-Acetylneuraminic acid (Neu5Ac) forms the highly fluorophoric quinoxalinone derivative (Q) when treated with 1,2-diamino-4, 5-methylenedioxybenzene (DMB). Effects of protonation and deprotonation on the fluorescence of Q were examined at room temperature. The strong fluorescence was found to be caused by the neutral form Q but not the protonated form of its excited state [Q]* and at pH below 1 the emission was completely quenched. The deprotonated singlet form [Q(-)]* was a less efficient fluorescer than [Q]*. (C) 2000 Elsevier Science Ltd. All rights reserved.
• Elevated concentrations of Neu5Ac and Neu5,9Ac2 in human plasma: potential biomarkers of cardiovascular disease
  作者：Jack Cheeseman、Concepcion Badia、Georgia Elgood-Hunt、Richard A. Gardner、Duong N. Trinh、Marco P. Monopoli、Gunter Kuhnle、Daniel I.R. Spencer、Helen M.I. Osborn

  DOI：10.1007/s10719-023-10138-3

  日期：2023.12

  Cardiovascular disease (CVD) is a group of health conditions affecting the heart and vascular system with very high prevalence and mortality rates. The presence of CVD is characterised by high levels of inflammation which have previously been associated with increased plasma concentrations of N-acetyl neuraminic acid (Neu5Ac). While Neu5Ac has been studied in the context of CVD, Neu5,9Ac₂ has not, despite being the second most abundant sialic acid in human plasma. A small-scale pilot study of thirty plasma samples from patients with diagnosed CVD, and thirty age and sex-matched healthy controls, was designed to gain insight into sialic acids as biomarkers for CVD and potential future areas of study. Each sample was assayed for Neu5Ac and Neu5,9Ac₂ concentrations. Mean Neu5Ac and Neu5,9Ac₂ concentrations were significantly elevated in patients with CVD compared to healthy controls (Neu5Ac: P < 0.001; Neu5,9Ac₂: P < 0.04). Receiver operator curve (ROC) analysis indicated that both Neu5Ac and Neu5,9Ac₂ have reasonable predictive power for the presence of CVD (Neu5Ac AUC: 0.86; Neu5,9Ac₂ AUC: 0.71). However, while Neu5Ac had both good sensitivity (0.82) and specificity (0.81), Neu5,9Ac₂ had equivalent specificity (0.81) but very poor sensitivity (0.44). A combination marker of Neu5Ac + Neu5,9Ac₂ showed improvement over Neu5Ac alone in terms of predictive power (AUC: 0.93), sensitivity (0.87), and specificity (0.90). Comparison to a known inflammatory marker, high sensitivity c-reactive protein (hs-CRP: P-value: NS, ROC:0.50) was carried out, showing that both Neu5Ac and Neu5,9Ac₂ outperformed this marker. Further to this, hs-CRP values were combined with the three different sialic acid markers to determine any effect on the AUC values. A slight improvement in AUC was noted for each of the combinations, with Neu5Ac + Neu5,9Ac₂ + hs-CRP giving the best AUC of 0.97 overall. Thus, Neu5Ac would appear to offer good potential as a predictive marker for the presence of CVD, which the addition of Neu5,9Ac₂ predictive power improves, with further improvement seen by the addition of hs-CRP.

  摘要心血管疾病（CVD）是一组影响心脏和血管系统的健康问题，发病率和死亡率都非常高。心血管疾病的特征是高水平的炎症，而炎症与血浆中 N-乙酰神经氨酸（Neu5Ac）浓度的升高有关。尽管 Neu5Ac 是人体血浆中含量第二高的硅醛酸，但却没有针对心血管疾病研究过 Neu5,9Ac2。为了深入了解作为心血管疾病生物标记物的硅酸以及未来潜在的研究领域，我们设计了一项小规模试验研究，研究对象是 30 名确诊心血管疾病的患者以及 30 名年龄和性别匹配的健康对照者。每个样本都检测了 Neu5Ac 和 Neu5,9Ac2 的浓度。与健康对照组相比，心血管疾病患者的平均 Neu5Ac 和 Neu5,9Ac2 浓度明显升高（Neu5Ac：P < 0.001；Neu5,9Ac2：P < 0.04）。接收运算曲线（ROC）分析表明，Neu5Ac 和 Neu5,9Ac2 对心血管疾病都有合理的预测能力（Neu5Ac AUC：0.86；Neu5,9Ac2 AUC：0.71）。然而，Neu5Ac 的灵敏度（0.82）和特异性（0.81）都很好，而 Neu5,9Ac2 的特异性（0.81）相当，但灵敏度（0.44）很差。Neu5Ac + Neu5,9Ac2组合标记物的预测能力（AUC：0.93）、灵敏度（0.87）和特异性（0.90）均优于单独的Neu5Ac。与已知的炎症标记物高灵敏度 c 反应蛋白（hs-CRP：P 值：NS，ROC：0.50）进行比较后发现，Neu5Ac 和 Neu5,9Ac2 均优于该标记物。此外，还将 hs-CRP 值与三种不同的硅酸标记物相结合，以确定对 AUC 值的影响。每种组合的 AUC 值都略有提高，其中 Neu5Ac + Neu5,9Ac2 + hs-CRP 的 AUC 值最高，为 0.97。由此看来，Neu5Ac 作为心血管疾病的预测标志物具有很好的潜力，加入 Neu5,9Ac2 可提高预测能力，加入 hs-CRP 可进一步提高预测能力。