乙基5-(4-硝基苯基)-5-氧代戊酸酯 | 898777-59-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 乙基5-(4-硝基苯基)-5-氧代戊酸酯
• 英文名称: ethyl 5-(4-nitrophenyl)-5-oxopentanoate
• 英文别名: Ethyl 5-(4-nitrophenyl)-5-oxovalerate
• CAS: 898777-59-8
• 化学式: C₁₃H₁₅NO₅
• 分子量: 265.266
• InChiKey: PYDJNTHFFDADIE-UHFFFAOYSA-N

物化性质

• 沸点：
  408.1±25.0 °C(Predicted)
• 密度：
  1.212±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  19
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  89.2
• 氢给体数：
  0
• 氢受体数：
  5

安全信息

• 海关编码：
  2918300090

反应信息

• 作为反应物：
  描述：

  乙基5-(4-硝基苯基)-5-氧代戊酸酯 在 palladium on activated carbon 、 氢气 作用下， 以 甲醇 为溶剂， 20.0 ℃ 、100.0 kPa 条件下， 反应 3.0h， 以65%的产率得到(±)-ethyl 5-(4-aminophenyl)-5-hydroxypentanoate
  参考文献：
  名称：

  Identification of the subtype-selective Sirt5 inhibitor balsalazide through systematic SAR analysis and rationalization via theoretical investigations

  摘要：

  We report here an extensive structure-activity relationship study of balsalazide, which was previously identified in a high-throughput screening as an inhibitor of Sirt5. To get a closer understanding why this compound is able to inhibit Sirt5, we initially performed docking experiments comparing the binding mode of a succinylated peptide as the natural substrate and balsalazide with Sirt5 in the presence of NAD(+). Based on the evidence gathered here, we designed and synthesized 13 analogues of balsalazide, in which single functional groups were either deleted or slightly altered to investigate which of them are mandatory for high inhibitory activity. Our study confirms that balsalazide with all its given functional groups is an inhibitor of Sirt5 in the low micromolar concentration range and structural modifications presented in this study did not increase potency. While changes on the N-aroyl-beta-alanine side chain eliminated potency, the introduction of a truncated salicylic acid part minimally altered potency. Calculations of the associated reaction paths showed that the inhibition potency is very likely dominated by the stability of the inhibitor-enzyme complex and not the type of inhibition (covalent vs. non-covalent). Further in-vitro characterization in a trypsin coupled assay determined that the tested inhibitors showed no competition towards NAD(+) or the synthetic substrate analogue ZKsA. In addition, investigations for subtype selectivity revealed that balsalazide is a subtype-selective Sirt5 inhibitor, and our initial SAR and docking studies pave the way for further optimization. (C) 2020 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2020.112676
• 作为产物：
  描述：

  对硝基苯乙酮 在 哌啶 作用下， 以 乙醇 、 正己烷 为溶剂， 反应 264.67h， 生成 乙基5-(4-硝基苯基)-5-氧代戊酸酯
  参考文献：
  名称：

  Identification of the subtype-selective Sirt5 inhibitor balsalazide through systematic SAR analysis and rationalization via theoretical investigations

  摘要：

  We report here an extensive structure-activity relationship study of balsalazide, which was previously identified in a high-throughput screening as an inhibitor of Sirt5. To get a closer understanding why this compound is able to inhibit Sirt5, we initially performed docking experiments comparing the binding mode of a succinylated peptide as the natural substrate and balsalazide with Sirt5 in the presence of NAD(+). Based on the evidence gathered here, we designed and synthesized 13 analogues of balsalazide, in which single functional groups were either deleted or slightly altered to investigate which of them are mandatory for high inhibitory activity. Our study confirms that balsalazide with all its given functional groups is an inhibitor of Sirt5 in the low micromolar concentration range and structural modifications presented in this study did not increase potency. While changes on the N-aroyl-beta-alanine side chain eliminated potency, the introduction of a truncated salicylic acid part minimally altered potency. Calculations of the associated reaction paths showed that the inhibition potency is very likely dominated by the stability of the inhibitor-enzyme complex and not the type of inhibition (covalent vs. non-covalent). Further in-vitro characterization in a trypsin coupled assay determined that the tested inhibitors showed no competition towards NAD(+) or the synthetic substrate analogue ZKsA. In addition, investigations for subtype selectivity revealed that balsalazide is a subtype-selective Sirt5 inhibitor, and our initial SAR and docking studies pave the way for further optimization. (C) 2020 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2020.112676

文献信息

• Synthesis and Binding Studies of a Tetra-α Aryl-Extended Photoresponsive Calix[4]pyrrole Receptor Bearing <i>meso</i> -Alkyl Substituents
  作者：Luis Escobar、Frank A. Arroyave、Pablo Ballester

  DOI：10.1002/ejoc.201701602

  日期：2018.3.7

  Synthesis of the tetra‐α isomer of a meso‐azobenzene‐extended calix[4]pyrrole and photo‐irradiation of the all‐trans receptor induces the isomerization of its azobenzene units, producing a mixture enriched with the cis‐counterpart. Its interaction with electron‐rich molecular guests (neutral and anionic) was probed using 1H NMR spectroscopic titrations and isothermal titration calorimetry (ITC).

  内消旋偶氮苯延伸的杯[4]吡咯的四α异构体的合成和全反式受体的光辐射诱导了其偶氮苯单元的异构化，产生了富含顺式对映体的混合物。使用1 H NMR光谱滴定法和等温滴定量热法（ITC）探测了它与富电子分子客体（中性和阴离子）的相互作用。
• Stereoselective Synthesis of Lower and Upper Rim Functionalized Tetra-α Isomers of Calix[4]pyrroles
  作者：Alejandro Díaz-Moscoso、Daniel Hernández-Alonso、Luis Escobar、Frank A. Arroyave、Pablo Ballester

  DOI：10.1021/acs.orglett.6b03505

  日期：2017.1.6

  Hydroxyaryl alkyl ketones with functionalized alkyl chains often fail to produce the corresponding tetra-α calix[4]pyrroles in Brönsted acid mediated condensations with pyrrole. A remarkable effect exerted by the addition of methyltrialkylammonium chloride during the acid-mediated syntheses of a series of meso-(tetrahydroxyaryl)-meso-tetraalkylcalix[4]pyrroles featuring alkyl terminal chloro or ester

  具有官能化烷基链的羟基芳基烷基酮通常无法在布朗斯台德酸介导的与吡咯的缩合反应中产生相应的四-α杯[4]吡咯。据报道，在酸介导的一系列具有烷基末端氯或酯基的内消旋-（四羟基芳基）-内消旋-四烷基杯[4]吡咯的酸介导的合成过程中，加入甲基三烷基氯化铵可产生显着效果。铵盐增强了环缩合反应，并诱导了几乎所有四-α异构体的排他性形成。
• Generation and reaction of alkyl radicals in open reaction vessels
  作者：Elene Tatunashvili、Christopher S. P. McErlean

  DOI：10.1039/d0ob01892a

  日期：——

  alkyl iodides into reactive alkyl radicals is described. Aryl diazonium salts react with Hantzsch esters and molecular oxygen to give aryl radicals, which participate in halogen atom transfers to give alkyl radicals. These intermediates react with a variety of acceptors. The reaction cascade occurs at room temperature, in open reaction vessels, with short reaction times.

  描述了一种将烷基碘转化为反应性烷基自由基的操作简单的方法。芳基重氮盐与 Hantzsch 酯和分子氧反应生成芳基自由基，芳基自由基参与卤素原子转移生成烷基自由基。这些中间体与多种受体反应。反应级联发生在室温下，在开放的反应容器中，反应时间短。
• Synthesis and Dimerization Studies of a Lipophilic Photoresponsive Aryl-Extended Tetraurea-Calix[4]pyrrole
  作者：Ryo Sekiya、Alejandro Díaz-Moscoso、Pablo Ballester

  DOI：10.1002/chem.201704777

  日期：2018.2.9

  We describe the syntheses of the lipophilic aryl‐extended α,α,α,α‐tetraurea‐phenyl‐calix[4]pyrrole 1, featuring four appended azo‐phenyl groups with two tert‐butoxy carbonyl meta‐substituents and its photo‐inactive counterpart 2. In CD2Cl2 solutions, both tetraurea‐calix[4]pyrroles self‐assemble into dimeric capsules by encapsulating one molecule of a suitable bis‐N‐oxide or two molecules of a mono‐N‐oxide

  我们描述了亲脂性的芳基-延长α，α，α的合成，α-四脲苯基杯[4]吡咯1，设有具有四个所附偶氮苯基基团的两种叔丁氧基羰基间位-取代基和其光无活性的对应2。在CD 2 Cl 2溶液中，两个四脲杯[4]吡咯通过封装一分子合适的双N氧化物或两分子单N氧化物而自组装成二聚体胶囊。二聚体胶囊主要通过在八个单向取向的脲基团之间建立的十六个氢键的环状阵列来稳定。光辐照实验证明了反式-到-顺偶氮苯基团和立体异构过多的形成的异构化顺式偶氮-富集荚膜组件。高度顺式偶氮富集的荚膜组件似乎显示出降低的稳定性，并且它们与也与N氧化物结合的非荚膜对等体参与平衡。热致顺至-反式互变过程证明了光致异构化的可逆性和最具约束力的合作伙伴的耐光性。两个四脲的等摩尔混合物以接近统计分布的比例产生了两个同二聚体胶囊和异二聚体对应物。
• Functional-Group-Tolerant Pd-Catalyzed Carbonylative Negishi Coupling with Aryl Iodides
  作者：Dmitrii V. Kalinin、Trond Ulven

  DOI：10.1021/acs.joc.3c00948

  日期：2023.12.1

  A chemoselective Pd-mediated carbonylative Negishi-type catalytic protocol for the synthesis of (hetero)aryl ketones is reported. The protocol employs the PEPPSI-IPr precatalyst and CO gas at atmospheric pressure (balloon) to foster the carbonylative coupling between diverse C(sp3)-hybridized organozinc reagents and a broad range of aryl iodides, including substrates carrying aldehyde, aniline, phenol

  报道了一种用于合成（杂）芳基酮的化学选择性 Pd 介导的羰基化 Negishi 型催化方案。该协议采用 PEPPSI-IPr 预催化剂和 CO 气体在大气压（气球）下促进多种 C(sp 3 ) 杂化有机锌试剂和各种芳基碘化物之间的羰基化偶联，包括携带醛、苯胺、苯酚、或羧酸基团和杂芳基。