N-(1,4-二氢-1,4-二氧-2-萘)-L-色氨酸 | 185351-19-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 中文名称: N-(1,4-二氢-1,4-二氧-2-萘)-L-色氨酸
• 英文名称: NQTrp
• 英文别名: (2S)-2-[(1,4-dioxonaphthalen-2-yl)amino]-3-(1H-indol-3-yl)propanoic acid
• CAS: 185351-19-3
• 化学式: C₂₁H₁₆N₂O₄
• 分子量: 360.369
• InChiKey: DZZUYZXINNHEGM-SFHVURJKSA-N

物化性质

• 熔点：
  208.0-211.0 °C
• 沸点：
  658.9±55.0 °C(Predicted)
• 密度：
  1.45±0.1 g/cm3(Predicted)
• 溶解度：
  在DMSO中的溶解度为20mg/mL，澄清

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  99.3
• 氢给体数：
  3
• 氢受体数：
  5

安全信息

• 储存条件：
  -20°C，密封保存于干燥处。

制备方法与用途

NQTrp是一种芳香萘醌色氨酸杂化分子，具有广泛的抗淀粉样变性作用，能抑制tau蛋白的聚集。在体外实验中，NQTrp能够抑制六肽（γD-晶状蛋白N端的41GCWMLY46）及全长γD-晶状蛋白的聚集。

反应信息

• 作为反应物：
  描述：

  氯甲基二甲基氯硅烷 、 N-(1,4-二氢-1,4-二氧-2-萘)-L-色氨酸 在 六甲基二硅氮烷 、 cesium fluoride 作用下， 以 二乙二醇二甲醚 为溶剂， 生成
  参考文献：
  名称：

  Methylations of Tryptophan-Modified Naphthoquinone Affect Its Inhibitory Potential toward Aβ Aggregation

  摘要：

  Aggregation of amyloid beta (A beta) is the hallmark of Alzheimer's disease (AD). Small molecules inhibiting A beta can be valuable therapeutics for AD. We have previously reported that 1,4-naphthoquinon-2-yk-tryptophan (NQTrp), reduces aggregation and oligomerization of A beta in vitro and in vivo. In silico analysis further showed that certain functional groups of NQTrp, not in the aromatic rings, are also involved in binding and inhibiting A beta. To better understand the exact mode of action and identify the groups crucial for NQTrp inhibitory activity, we conducted structure activity-analysis. Four derivatives of NQTrp were studied in silico: a D-isomer, two single-methylated and one double-methylated derivative. In silico results showed that the NQTrp groups involved in hydrogen bonds are the anilinic NH (i.e., the NH linker between the quinone and tryptophan moieties), the quinonic carbonyls, and the carboxylic acid. These predictions were supported by in vitro results. Our results should aid in designing improved small-molecule inhibitors of A beta aggregation for treating AD.

  DOI：

  10.1021/jp309066p
• 作为产物：
  描述：

  L-色氨酸 、 1,4-萘醌 以 乙醇 、 水 为溶剂， 反应 24.0h， 以53%的产率得到N-(1,4-二氢-1,4-二氧-2-萘)-L-色氨酸
  参考文献：
  名称：

  On the Synthesis of Naphthoquinonyl Heterocyclic Amino Acids

  摘要：

  L-组氨酸、N δ-cbz-L-组氨酸、L-色氨酸和 L-脯氨酸与 1,4-萘醌或 2,3-二氯-1,4-萘醌反应，生成改性的 N-醌基氨基酸。对于游离的δ-氨基酸，醌分子与δ-氨基相连。对于封端δ-氨基酸，醌分子连接到杂环氮原子上。

  DOI：

  10.1055/s-1996-4417

文献信息

• Efficient Syntheses of Naphthoquinone-Dipeptides
  作者：Alan Katritzky、Longchuan Huang、Rajeev Sakhuja

  DOI：10.1055/s-0029-1220012

  日期：2010.6

  Naphthoquinone-dipeptides are synthesized in 76-89% yield from naphthoquinone-amino acid conjugates by N-acylbenzotriazole methodology in aqueous media at 20 ˚C.

  萘醌二肽通过 N-酰基苯基三氮唑法在水相中于 20°C 从萘醌-氨基酸共轭物合成，产率为 76-89%。
• New family of antimicrobial agents derived from 1,4-naphthoquinone
  作者：Monika Janeczko、Oleg M. Demchuk、Dorota Strzelecka、Konrad Kubiński、Maciej Masłyk

  DOI：10.1016/j.ejmech.2016.10.034

  日期：2016.11

  Naphthalene-1,4-dione derivatives were synthesized and tested against selected bacterial strains. All the tested compounds were prepared by direct introduction of corresponding substituents into the naphthoquinone core in oxidative conditions. In this study, eight strains of bacteria (Proteus, Escherichia, Klebsiella, Staphylococcus, Enterobacter, Pseudomonas, Salmonella, Enterococcus) were used for

  合成萘-1,4-二酮衍生物，并针对选定的细菌菌株进行测试。通过在氧化条件下将相应的取代基直接引入萘醌核中来制备所有测试的化合物。在这项研究中，八株细菌（变形杆菌，大肠杆菌，克雷伯菌，金黄色葡萄球菌，肠杆菌，假单胞菌，沙门氏菌，肠球菌）用于通过最小抑制浓度（MIC）方法测定合成化合物的抗菌活性。另外，使用人红细胞测试了所选化合物的溶血活性。所有萘-1,4-二酮衍生物均显示出显着的抗菌活性，MIC值为7.8至500μg/ ml。大多数合成的化合物显示出对金黄色葡萄球菌最强的抗菌性能，并且具有很高的选择性。测试的萘-1,4-二酮衍生物均未表现出溶血活性。
• On the Synthesis of Naphthoquinonyl Heterocyclic Amino Acids
  作者：Prativa Bade Shrestha-Dawadi、Shmuel Bittner、Mati Fridkin、Shai Rahimipour

  DOI：10.1055/s-1996-4417

  日期：1996.12

  L-Histidine, N α -cbz-L-histidine, L-tryptophan and L-proline react with 1,4-naphthoquinone or 2,3-dichloro-1,4-naphthoquinone to afford modified N-quinonyl amino acids. With free α-amino acids, the quinone moiety is attached to the α-amino group. With blocked α-amino acids the quinone moiety is attached to the heterocyclic nitrogen atom.

  L-组氨酸、N δ-cbz-L-组氨酸、L-色氨酸和 L-脯氨酸与 1,4-萘醌或 2,3-二氯-1,4-萘醌反应，生成改性的 N-醌基氨基酸。对于游离的δ-氨基酸，醌分子与δ-氨基相连。对于封端δ-氨基酸，醌分子连接到杂环氮原子上。
• Methylations of Tryptophan-Modified Naphthoquinone Affect Its Inhibitory Potential toward Aβ Aggregation
  作者：Roni Scherzer-Attali、Marino Convertino、Riccardo Pellarin、Ehud Gazit、Daniel Segal、Amedeo Caflisch

  DOI：10.1021/jp309066p

  日期：2013.2.14

  Aggregation of amyloid beta (A beta) is the hallmark of Alzheimer's disease (AD). Small molecules inhibiting A beta can be valuable therapeutics for AD. We have previously reported that 1,4-naphthoquinon-2-yk-tryptophan (NQTrp), reduces aggregation and oligomerization of A beta in vitro and in vivo. In silico analysis further showed that certain functional groups of NQTrp, not in the aromatic rings, are also involved in binding and inhibiting A beta. To better understand the exact mode of action and identify the groups crucial for NQTrp inhibitory activity, we conducted structure activity-analysis. Four derivatives of NQTrp were studied in silico: a D-isomer, two single-methylated and one double-methylated derivative. In silico results showed that the NQTrp groups involved in hydrogen bonds are the anilinic NH (i.e., the NH linker between the quinone and tryptophan moieties), the quinonic carbonyls, and the carboxylic acid. These predictions were supported by in vitro results. Our results should aid in designing improved small-molecule inhibitors of A beta aggregation for treating AD.