butyl (2,5-dioxopyrrolidin-1-yl)carbonate | 64562-12-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: butyl (2,5-dioxopyrrolidin-1-yl)carbonate
• 英文别名: N-(butoxycarbonyloxy)succinimide；Butyl (2,5-dioxopyrrolidin-1-yl) carbonate
• CAS: 64562-12-5
• 化学式: C₉H₁₃NO₅
• 分子量: 215.206
• InChiKey: CFEOGXPQZRXPMM-UHFFFAOYSA-N

物化性质

• 沸点：
  287.8±23.0 °C(Predicted)
• 密度：
  1.27±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  15
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  72.9
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  butyl (2,5-dioxopyrrolidin-1-yl)carbonate 在 N-甲基吗啉 、 sodium hydride 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 7.0h， 生成
  参考文献：
  名称：

  单步荧光sirtuin检测方法的开发及其在高通量筛选中的应用

  摘要：

  Sirtuins (SIRT) 是一类烟酰胺腺嘌呤二核苷酸 (NAD + ) 依赖性组蛋白脱乙酰酶。由于 SIRT 具有不同的亚细胞位置和对脱酰活性的不同偏好，SIRT 不仅在生物学功能上具有重要意义，而且在人类疾病中也具有重要意义。因此，建立高通量筛选方法对于快速、准确地发现SIRT调节剂具有重要意义。本研究基于SIRTs的不同赖氨酸底物，设计合成了小分子4a~d作为荧光探针，其可以被SIRTs识别和催化，然后自发的分子内酯交换反应发出荧光。我们对这些具有不同 SIRT 的荧光探针进行了全面研究，以进行测定优化、验证、动力学、参数和高通量筛选形式的应用。我们预计这些探针将为高效发现更多 SIRT 抑制剂提供有用且强大的工具。

  DOI：

  10.1039/d1ob02347k
• 作为产物：
  描述：

  N,N'-二琥珀酰亚胺基碳酸酯 、 正丁醇 在 三乙胺 作用下， 以 乙腈 为溶剂， 反应 3.0h， 以73%的产率得到butyl (2,5-dioxopyrrolidin-1-yl)carbonate
  参考文献：
  名称：

  Development of a Fluorogenic Probe with a Transesterification Switch for Detection of Histone Deacetylase Activity

  摘要：

  Histone deacetylases (HDACs) are key enzymatic regulators of many cellular processes such as gene expression, cell cycle, and tumorigenesis. These enzymes are attractive targets for drug development. However, very few simple methods for monitoring HDAC activity have been reported. Here, we have developed a fluorogenic probe, K4(Ac)-CCB, which consists of the histone H3 peptide containing acetyl-Lys and a coumarin fluorophore with a carbonate ester. By the simple addition of the probe to a HDAC solution, enzyme activity was clearly detected through spontaneous intramolecular transesterification, which renders the probe fluorescent. In addition, K4(Ac)-CCB can be applied to the evaluation of HDAC inhibitor activity. This is the first report to demonstrate the monitoring of HDAC activity by using a one-step procedure. Thus, our novel fluorogenic probe will provide a powerful tool for epigenetic research and the discovery of HDAC-targeted drugs.

  DOI：

  10.1021/ja306045j

文献信息

• Intramolecular Long-Distance Nucleophilic Reactions as a Rapid Fluorogenic Switch Applicable to the Detection of Enzymatic Activity
  作者：Reisuke Baba、Yuichiro Hori、Kazuya Kikuchi

  DOI：10.1002/chem.201406093

  日期：2015.3.16

  Long‐distance intramolecular nucleophilic reactions are promising strategies for the design of fluorogenic probes to detect enzymatic activity involved in lysine modifications. However, such reactions have been challenging and hence have not been established. In this study, we have prepared fluorogenic peptides that induce intramolecular reactions between lysine nucleophiles and electrophiles in distal

  长距离分子内亲核反应是设计荧光探针以检测涉及赖氨酸修饰的酶活性的有前途的策略。但是，这种反应具有挑战性，因此尚未建立。在这项研究中，我们准备了荧光肽，可诱导远端位置的赖氨酸亲核试剂和亲电试剂之间的分子内反应。这些肽含有赖氨酸和带有碳酸酯的荧光猝灭荧光团，可引发亲核性酯交换反应，从而导致荧光反应。尽管在赖氨酸和荧光团之间存在长的九个氨基酸间隔基，但在温和的水性条件下仍发生了酯交换反应。此外，其中一种肽的反应动力学最快，半衰期为3.7分钟。此外，通过将这种荧光开关整合到探针中，可以快速荧光检测组蛋白脱乙酰基酶（HDAC）的活性。这些结果表明，酯交换反应具有很大的潜力，可以用作常规的荧光开关来监测赖氨酸靶向酶的活性。
• GLYCAN ARRAYS ON PTFE-LIKE ALUMINUM COATED GLASS SLIDES AND RELATED METHODS
  申请人：Wong Chi-Huey

  公开号：US20100016171A1

  公开（公告）日：2010-01-21

  Aluminum coated glass slides provide a novel glycan array platform. Specifically, aluminum coated glass slides increase sensitivity of fluorescent based assay methods. Additionally, aluminum coated glass slides allows for mass spectroscopic analysis of carbohydrates and provide a platform for examining activity of cellulases. The unique properties of ACG slides include: 1) the metal oxide layer on the surface can be activated for grafting organic compounds such as modified oligosaccharides; 2) the surface remains electrically conductive, and the grafted oligosaccharides can be simultaneously characterized by mass spectrometry and carbohydrate-binding assay; and 3) the slides are more sensitive than transparent glass slides in binding analysis.

  铝涂层玻璃载玻片提供了一种新的糖基阵列平台。具体而言，铝涂层玻璃载玻片增加了荧光基础检测方法的灵敏度。此外，铝涂层玻璃载玻片允许对碳水化合物进行质谱分析，并提供了检查纤维素酶活性的平台。ACG载玻片的独特性质包括：1）表面的金属氧化物层可以被激活，以嫁接有机化合物，如修饰的寡糖；2）表面仍然具有电导性，嫁接的寡糖可以同时通过质谱分析和糖类结合分析进行表征；3）与透明玻璃载玻片相比，这些载玻片在结合分析中更为敏感。
• Glycan arrays on PTFE-like aluminum coated glass slides and related methods
  申请人：Academia Sinica

  公开号：US10274488B2

  公开（公告）日：2019-04-30

  Aluminum coated glass slides provide a novel glycan array platform. Specifically, aluminum coated glass slides increase sensitivity of fluorescent based assay methods. Additionally, aluminum coated glass slides allows for mass spectroscopic analysis of carbohydrates and provide a platform for examining activity of cellulases. The unique properties of ACG slides include: 1) the metal oxide layer on the surface can be activated for grafting organic compounds such as modified oligosaccharides; 2) the surface remains electrically conductive, and the grafted oligosaccharides can be simultaneously characterized by mass spectrometry and carbohydrate-binding assay; and 3) the slides are more sensitive than transparent glass slides in binding analysis.

  镀铝玻璃载玻片提供了一种新型糖阵列平台。具体来说，镀铝玻璃载玻片提高了荧光检测方法的灵敏度。此外，铝涂层玻璃载玻片还可用于碳水化合物的质谱分析，并为纤维素酶活性的检测提供平台。ACG 玻片的独特性能包括1) 表面的金属氧化物层可被激活，用于接枝有机化合物，如改性低聚糖；2) 表面保持导电性，接枝的低聚糖可同时通过质谱分析和碳水化合物结合分析进行表征；3) 在结合分析方面，载玻片比透明玻璃载玻片更灵敏。
• SAR Studies on Trisubstituted Benzimidazoles as Inhibitors of <i>Mtb</i> FtsZ for the Development of Novel Antitubercular Agents
  作者：Divya Awasthi、Kunal Kumar、Susan E. Knudson、Richard A. Slayden、Iwao Ojima

  DOI：10.1021/jm401468w

  日期：2013.12.12

  FtsZ, an essential protein for bacterial cell division, is a highly promising therapeutic target, especially for the discovery and development of new-generation anti-TB agents. Following up the identification of two lead 2,5,6-trisubstituted benzimidazoles, 1 and 2, targeting Mtb-FtsZ in our previous study, an extensive SAR study for optimization of these lead compounds was performed through systematic modification of the 5 and 6 positions. This study has successfully led to the discovery of a highly potent advanced lead 5f (MIC = 0.06 mu g/mL) and several other compounds with comparable potencies. These advanced lead compounds possess a dimethylamino group at the 6 position. The functional groups at the 5 position exhibit substantial effects on the antibacterial activity as well. In vitro experiments such as the FtsZ polymerization inhibitory assay and TEM analysis of Mtb-FtsZ treated with 5f and others indicate that Mtb-FtsZ is the molecular target for their antibacterial activity.
• Design, synthesis and evaluation of novel 2,5,6-trisubstituted benzimidazoles targeting FtsZ as antitubercular agents
  作者：Bora Park、Divya Awasthi、Soumya R. Chowdhury、Eduard H. Melief、Kunal Kumar、Susan E. Knudson、Richard A. Slayden、Iwao Ojima

  DOI：10.1016/j.bmc.2014.03.035

  日期：2014.5

  Filamenting temperature-sensitive protein Z (FtsZ), an essential cell division protein, is a promising target for the drug discovery of new-generation antibacterial agents against various bacterial pathogens. As a part of SAR studies on benzimidazoles, we have synthesized a library of 376 novel 2,5,6-trisubstituted benzimidazoles, bearing ether or thioether linkage at the 6-position. In a preliminary HTP screening against Mtb H37Rv, 108 compounds were identified as hits at a cut off concentration of 5 mu g/mL. Among those hits, 10 compounds exhibited MIC values in the range of 0.63-12.5 mu g/mL. Light scattering assay and TEM analysis with the most potent compound 5a clearly indicate that its molecular target is Mtb-FtsZ. Also, the K-d of 5a with Mtb-FtsZ was determined to be 1.32 mu M. (C) 2014 Elsevier Ltd. All rights reserved.