2-[4-(1-Ethyl-2,5-dioxopyrrolidin-3-yl)sulfanylphenyl]acetic acid | 1336858-35-5

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: 2-[4-(1-Ethyl-2,5-dioxopyrrolidin-3-yl)sulfanylphenyl]acetic acid
• CAS: 1336858-35-5
• 化学式: C₁₄H₁₅NO₄S
• 分子量: 293.343
• InChiKey: DPMVUWAYQOMMPO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  20
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  100
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  谷胱甘肽 、 2-[4-(1-Ethyl-2,5-dioxopyrrolidin-3-yl)sulfanylphenyl]acetic acid 以 water-d2 为溶剂， 反应 24.0h， 生成
  参考文献：
  名称：

  Tunable Degradation of Maleimide–Thiol Adducts in Reducing Environments

  摘要：

  Addition chemistries are widely used in preparing biological conjugates, and in particular, maleimide-thiol adducts have been widely employed. Here, we show that the resulting succinimide thioether formed by the Michael-type addition of thiols to N-ethylmaleimide (NEM), generally accepted as stable, undergoes retro and exchange reactions in the presence of other thiol compounds at physiological pH and temperature, offering a novel strategy for controlled release. Model studies (H-1 NMR, HPLC) of NEM conjugated to 4-mercaptophenylcetic acid (MPA), N-acetylcysteine, or 3-mercaptopropionic acid (MP) incubated with glutathione showed half-lives of conversion from 20 to 80 h, with extents of conversion from 20% to 90% for MPA and N-acetylcysteine conjugates. After ring-opening, the resultant succinimide thioether did not show retro and exchange reactions.The kinetics of the retro reactions and extent of exchange can be modulated by the Michael donor's reactivity; therefore, the degradation of maleimide-thiol adducts could be tuned for controlled release of drugs or degradation of materials at time scales different than those currently possible via disulfide-mediated release. Such approaches may find a new niche for controlled release in reducing environments relevant in chemotherapy and subecullar trafficking.

  DOI：

  10.1021/bc200148v
• 作为产物：
  描述：

  N-乙基马来酰亚胺 、 4-巯基苯基乙酸 在 三乙胺 作用下， 以 乙腈 为溶剂， 反应 1.0h， 以90%的产率得到2-[4-(1-Ethyl-2,5-dioxopyrrolidin-3-yl)sulfanylphenyl]acetic acid
  参考文献：
  名称：

  谷胱甘肽介导的巯基-马来酰亚胺偶联物的降解。

  摘要：

  响应于含硫醇的环境，硫醚琥珀酰亚胺点击键的复古迈克尔型加成和硫醇交换为设计可控药物递送的谷胱甘肽敏感的可降解水凝胶提供了一种新颖的策略。在这里我们表征了动力学和逆向迈克尔型加成和硫醇交换程度与硫醇的p K a和马来酰亚胺的N-取代基的身份的变化。通过典型的迈克尔型加成制备了一系列的N-取代的硫醚琥珀酰亚胺。结合到N-乙基马来酰亚胺（NEM），N-苯基马来酰亚胺（NPM）上的4-巯基苯乙酸（MPA，p K a 6.6）的模型研究（1 H NMR，HPLC）或N-氨乙基马来酰亚胺（NAEM），然后与谷胱甘肽一起孵育，显示半衰期为3.1到18 h，转化率约为12％到90％。交换速率和水解开环速率的变化似乎是由共振效应，N-取代的部分的吸电子能力以及胺取代基与水的分子内催化氢键合的电势引起的（尤其是在这种情况下）开环）。4-巯基肉桂酸（MPP，p K a 7.0）和N-乙酰基-1-半胱氨酸（NAC，p

  DOI：

  10.1021/acs.bioconjchem.8b00546

文献信息

• Manipulation of Glutathione-Mediated Degradation of Thiol–Maleimide Conjugates
  作者：Haocheng Wu、Paige J. LeValley、Tianzhi Luo、April M. Kloxin、Kristi L. Kiick

  DOI：10.1021/acs.bioconjchem.8b00546

  日期：2018.11.21

  effects, electron-withdrawing capacity of the N-substituted moiety, as well as the potential for intramolecular catalytic hydrogen bonding of amine substituents with water (particularly in the case of ring opening). Further model studies of 4-mercaptohydrocinnamic acid (MPP, pKa 7.0) and N-acetyl-l-cysteine (NAC, pKa 9.5) conjugated to selected N-substituted maleimides and then incubated with glutathione

  响应于含硫醇的环境，硫醚琥珀酰亚胺点击键的复古迈克尔型加成和硫醇交换为设计可控药物递送的谷胱甘肽敏感的可降解水凝胶提供了一种新颖的策略。在这里我们表征了动力学和逆向迈克尔型加成和硫醇交换程度与硫醇的p K a和马来酰亚胺的N-取代基的身份的变化。通过典型的迈克尔型加成制备了一系列的N-取代的硫醚琥珀酰亚胺。结合到N-乙基马来酰亚胺（NEM），N-苯基马来酰亚胺（NPM）上的4-巯基苯乙酸（MPA，p K a 6.6）的模型研究（1 H NMR，HPLC）或N-氨乙基马来酰亚胺（NAEM），然后与谷胱甘肽一起孵育，显示半衰期为3.1到18 h，转化率约为12％到90％。交换速率和水解开环速率的变化似乎是由共振效应，N-取代的部分的吸电子能力以及胺取代基与水的分子内催化氢键合的电势引起的（尤其是在这种情况下）开环）。4-巯基肉桂酸（MPP，p K a 7.0）和N-乙酰基-1-半胱氨酸（NAC，p
• Tunable Degradation of Maleimide–Thiol Adducts in Reducing Environments
  作者：Aaron D. Baldwin、Kristi L. Kiick

  DOI：10.1021/bc200148v

  日期：2011.10.19

  Addition chemistries are widely used in preparing biological conjugates, and in particular, maleimide-thiol adducts have been widely employed. Here, we show that the resulting succinimide thioether formed by the Michael-type addition of thiols to N-ethylmaleimide (NEM), generally accepted as stable, undergoes retro and exchange reactions in the presence of other thiol compounds at physiological pH and temperature, offering a novel strategy for controlled release. Model studies (H-1 NMR, HPLC) of NEM conjugated to 4-mercaptophenylcetic acid (MPA), N-acetylcysteine, or 3-mercaptopropionic acid (MP) incubated with glutathione showed half-lives of conversion from 20 to 80 h, with extents of conversion from 20% to 90% for MPA and N-acetylcysteine conjugates. After ring-opening, the resultant succinimide thioether did not show retro and exchange reactions.The kinetics of the retro reactions and extent of exchange can be modulated by the Michael donor's reactivity; therefore, the degradation of maleimide-thiol adducts could be tuned for controlled release of drugs or degradation of materials at time scales different than those currently possible via disulfide-mediated release. Such approaches may find a new niche for controlled release in reducing environments relevant in chemotherapy and subecullar trafficking.