ethyl 2-acetamido-2-propargyl-4-pentynoate | 191215-37-9

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: ethyl 2-acetamido-2-propargyl-4-pentynoate
• 英文别名: Ethyl 2-acetamido-2-prop-2-ynylpent-4-ynoate
• CAS: 191215-37-9
• 化学式: C₁₂H₁₅NO₃
• 分子量: 221.256
• InChiKey: ZIGMMIRFXODYCX-UHFFFAOYSA-N

物化性质

• 沸点：
  386.9±42.0 °C(Predicted)
• 密度：
  1.086±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  16
• 可旋转键数：
  6
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  55.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  ethyl 2-acetamido-2-propargyl-4-pentynoate 在 N-甲基吗啉 、 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 24.0h， 生成 (2S)-2-[(2-acetamido-2-prop-2-ynylpent-4-ynoyl)amino]-4-methylpentanoic acid
  参考文献：
  名称：

  三唑-肽缀合物作为 Aβ-聚集、金属介导的 Aβ-聚集和细胞毒性的调节剂

  摘要：

  淀粉样蛋白-β (Aβ) 聚集在阿尔茨海默病 (AD) 的发病机制中起着关键作用。与此同时，Cu 2+等氧化还原活性金属的存在进一步增强了 Aβ 聚集、氧化应激和细胞毒性。在这项研究中，我们合理地设计、合成和评估了一系列三唑-肽偶联物作为潜在的混杂配体，能够靶向 AD 的不同病理因素。特别地，拟肽 DS2 显示出对 Aβ 聚集的最佳抑制活性，IC 50值为 2.43 ± 0.05 μM。此外，DS2 分解预先形成的 Aβ 42原纤维，螯合金属离子，抑制金属介导的 Aβ 聚集，显着控制活性氧的产生，并减少氧化应激。DS2 表现出非常低的细胞毒性，并显着改善了分化的神经母细胞瘤细胞 SH-SY5Y 中 Aβ 诱导的毒性。此外，通过透射电子显微镜 (TEM) 图像验证了在存在和不存在 DS2 的情况下Aβ 42的纤维结构的改变。为了阐明 DS2 对 Aβ 聚集和原纤维结构分解的抑制机制，进行了分子动力学

  DOI：

  10.1021/acschemneuro.3c00041
• 作为产物：
  描述：

  ethyl 2-amino-2-propargyl-4-pentynoate 在 乙酸酐 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 以83%的产率得到ethyl 2-acetamido-2-propargyl-4-pentynoate
  参考文献：
  名称：

  Multi-target-directed triazole derivatives as promising agents for the treatment of Alzheimer’s disease

  摘要：

  A novel series of triazole-based compounds have been designed, synthesised and evaluated as multi-targetdirected ligands (MTDLs) against Alzheimer disease (AD). The triazole-based compounds have been designed to target four major AD hallmarks that include A beta aggregation, metal-induced A beta aggregation, metal dys-homeostasis and oxidative stress. Among the synthesised compounds, 6n having o-CF3 group on the phenyl ring displayed most potent inhibitory activity (96.89% inhibition, IC50 = 8.065 +/- 0.129 mu M) against A beta(42) aggregation, compared to the reference compound curcumin (95.14% inhibition, IC50 = 6.385 +/- 0.009 mu M). Compound 6n disassembled preformed A beta(42) aggregates as effectively as curcumin. Furthermore, 6n displayed metal chelating ability and significantly inhibited Cu2+-induced A beta(42) aggregation and disassembled preformed Cu2+-induced A beta(42) aggregates. 6n successfully controlled the generation of the reactive oxygen species (ROS) by preventing the copper redox cycle. In addition, 6n did not display cytotoxicity and was able to inhibit toxicity induced by A beta(42) aggregates in SH-SY5Y cells. The preferred binding regions and key interactions of 6n with A beta(42) monomer and A beta(42) protofibril structure was evaluated with molecular docking. Compound 6n binds preferably to the C-terminal region of A beta(42) that play a critical role in A beta(42) aggregation. The results of the present study highlight a novel triazole-based compound, 6n, as a promising MTDL against AD.

  DOI：

  10.1016/j.bioorg.2019.03.058

文献信息

• Synthesis and reactions of silicon containing cyclic α-amino acid derivatives
  作者：Sambasivarao Kotha、Enugurthi Brahmachary

  DOI：10.1016/j.jorganchem.2003.09.044

  日期：2004.1

  simple synthesis of a new amino acid derivative 5,6-bis(trimethylsilyl)indanylglycine via cobalt mediated [2 + 2 + 2] cycloaddition strategy is described. Co-trimerization of diyne building block containing amino acid moiety with bis(trimethylsilyl)acetylene in presence of CpCo(CO)2 catalyst afforded the silylated indane-based α-amino acid (AAA) derivative. Electrophilic aromatic substitution reaction

  描述了通过钴介导的[2 + 2 + 2]环加成策略简单合成新的氨基酸衍生物5,6-双（三甲基甲硅烷基）茚满基甘氨酸的方法。在CpCo（CO）2催化剂存在下，将含有氨基酸部分的二炔结构单元与双（三甲基甲硅烷基）乙炔共三聚，得到甲硅烷基化的基于茚满的α-氨基酸（AAA）衍生物。电芳族取代反应，本位到三甲基甲硅烷基都给高度官能化的基于二氢化茚-AAA衍生物。
• Design, Synthesis and Late‐Stage Modification of Indane‐Based Peptides via [2+2+2] Cyclotrimerization
  作者：Sambasivarao Kotha、Naveen Kumar Gupta、Gaddamedi Sreevani、Nageswara Rao Panguluri

  DOI：10.1002/asia.202100825

  日期：2021.11.15

  Indane-based peptides are biologically important compounds. Here, we carried out late stage modification of dipeptides containing 2-aminoindan-2-carboxylic acid (Aic) via Sonogashira coupling, [2+2+2] cyclotrimerization, sultine formation, Diels–Alder reaction and Suzuki–Miyaura cross coupling as key steps.

  基于茚满的肽是生物学上重要的化合物。在这里，我们通过 Sonogashira 偶联、[2+2+2] 环三聚、sultine 形成、Diels-Alder 反应和 Suzuki-Miyaura 交叉偶联作为关键对含有 2-氨基茚满-2-羧酸（Aic）的二肽进行后期修饰脚步。
• Synthesis of unsual α-amino acids via a 2+2+2 cycloaddition strategy
  作者：Sambasivarao Kotha、Enugurthi Brahmachary

  DOI：10.1016/s0040-4039(97)00663-1

  日期：1997.5

  A simple method for the preparation of di)ne building block 5 and its use in the synthesis of indane-based alpha-amino acid derivatives via a 2+2+2 cycloaddition strategy is reported. (C) 1997 Published by Elsevier Science Ltd.
• Synthesis of constrained phenylalanine derivatives via a [2+2+2] cycloaddition strategy
  作者：Sambasivarao Kotha、Enugurthi Brahmachary

  DOI：10.1016/s0968-0896(02)00039-1

  日期：2002.7

  A simple synthesis of dialkyne building blocks (6,7,8 and 9) embodying amino acid moiety is described. The dialkyne 6 participated in a [2 + 2+ 2] cycloaddition reaction with various monoalkynes in presence of Wilkinson's catalyst to give 5- and 5,6-disubstitued indan-based alpha-amino acid derivates. Cobalt catalyst [e.g., CpCo(CO)(2)] has also been employed in the synthesis of various 2-indanyl glycine derivatives via co-trimerization reaction of the diyne building blocks 6 and 7 with several monoalkynes. (C) 2002 Elsevier Science Ltd. All rights reserved.
• Serendipitous late-stage modification of dipeptide by using AIBN and thioacetic acid
  作者：Kotha, Sambasivarao、Gupta, Naveen Kumar、Ansari, Saima

  DOI：10.56042/ijc.v62i5.1431

  日期：——