[2-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-acryloylamino]-acetic acid methyl ester | 88143-88-8

• 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: [2-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-acryloylamino]-acetic acid methyl ester
• CAS: 88143-88-8
• 化学式: C₁₄H₁₂N₂O₅
• 分子量: 288.26
• InChiKey: MZIIDTHIXVNFKS-UHFFFAOYSA-N

物化性质

• 密度：
  1.392±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.09
• 重原子数：
  21.0
• 可旋转键数：
  4.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  92.78
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  、 [2-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-acryloylamino]-acetic acid methyl ester 在 N,N-二异丙基乙胺 、 溶剂红 43 作用下， 以 乙腈 为溶剂， 以30 %的产率得到methyl (3-(4'-chloro-6-(2-chloronicotinamido)-[1,1'-biphenyl]-3-yl)-2-(1,3-dioxoisoindolin-2-yl)propanoyl)glycinate
  参考文献：
  名称：

  Photocatalytic Functionalization of Dehydroalanine‐Derived Peptides in Batch and Flow

  摘要：

  Unnatural amino acids, and their synthesis by the late‐stage functionalization (LSF) of peptides, play a crucial role in areas such as drug design and discovery. Historically, the LSF of biomolecules has predominantly utilized traditional synthetic methodologies that exploit nucleophilic residues, such as cysteine, lysine or tyrosine. Herein, we present a photocatalytic hydroarylation process targeting the electrophilic residue dehydroalanine (Dha). This residue possesses an α,β‐unsaturated moiety and can be combined with various arylthianthrenium salts, both in batch and flow reactors. Notably, the flow setup proved instrumental for efficient scale‐up, paving the way for the synthesis of unnatural amino acids and peptides in substantial quantities. Our photocatalytic approach, being inherently mild, permits the diversification of peptides even when they contain sensitive functional groups. The readily available arylthianthrenium salts facilitate the seamless integration of Dha‐containing peptides with a wide range of arenes, drug blueprints, and natural products, culminating in the creation of unconventional phenylalanine derivatives. The synergistic effect of the high functional group tolerance and the modular characteristic of the aryl electrophile enables efficient peptide conjugation and ligation in both batch and flow conditions.

  DOI：

  10.1002/anie.202403271
• 作为产物：
  描述：

  N-Phthaloyl-L-serin 在 焦磷酸硫胺素 、 1-羟基苯并三唑 、 三乙胺 、 N,N'-二环己基碳二亚胺 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 23.0h， 生成 [2-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-acryloylamino]-acetic acid methyl ester
  参考文献：
  名称：

  肽直接化学转化为β-内酰胺

  摘要：

  通过与偶氮二羧酸酯和三苯基膦反应，在α'C上具有相对酸性质子（H 1为1）的适当保护的丝氨二肽可以有效地转化为β-内酰胺。将相同的反应条件应用于缺少酸性α'质子的丝氨酰胺可提供脱氢肽作为主要产物。描述了使这些结果合理化的模型反应和潜在的中间体。

  DOI：

  10.1016/s0040-4020(01)92149-0

文献信息

• A Vitamin B ₂ ‐Photocatalysed Approach to Methionine Analogues
  作者：Oliver J. Knowles 、Linus O. Johannissen、Giacomo E. M. Crisenza、Sam Hay、David Leys、David J. Procter

  DOI：10.1002/anie.202212158

  日期：2022.12.12

  role in medicinal and biological chemistry, synthetic methods to access non-natural methionine analogues remain underdeveloped. Using vitamin B2-photocatalysis, simple sulfides undergo radical α-C−H functionalization with unsaturated amino acid partners to deliver an array of new methionine derivatives. The approach also facilitates the chemoselective modification of peptide side-chains.

  尽管它们在医药和生物化学中发挥着新兴作用，但获取非天然甲硫氨酸类似物的合成方法仍不发达。使用维生素 B 2 -光催化，简单的硫化物与不饱和氨基酸伙伴发生自由基 α-C−H 官能化，产生一系列新的甲硫氨酸衍生物。该方法还有助于对肽侧链进行化学选择性修饰。
• Michael Addition Reaction between Dehydroalanines and Phosphites Enabled the Introduction of Phosphonates into Oligopeptides
  作者：Changjun Yu、Ruiyao E、Yingying An、Xiaomin Guo、Guangjun Bao、Yiping Li、Junqiu Xie、Wangsheng Sun

  DOI：10.1021/acs.orglett.4c01567

  日期：2024.6.7

  A method for introducing a range of phosphonates into oligopeptides through a Michael addition reaction between dehydroalanine and phosphite is presented. The method offers a mild, cheap, and straightforward approach to peptide phosphorylation that has potential applications in chemical biology and medicinal chemistry. Moreover, the introduction of a phosphonate group into short antibacterial peptides

  提出了一种通过脱氢丙氨酸和亚磷酸酯之间的迈克尔加成反应将一系列膦酸酯引入寡肽的方法。该方法提供了一种温和、廉价且直接的肽磷酸化方法，在化学生物学和药物化学方面具有潜在的应用。此外，将膦酸基团引入短抗菌肽中以证明其实用性，从而发现了具有有效广谱抗菌活性的膦酸化抗菌肽。