ethyl 2-oxo-5,5-dimethylhexanoate | 96056-57-4

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: ethyl 2-oxo-5,5-dimethylhexanoate
• 英文别名: Ethyl 5,5-dimethyl-2-oxohexanoate
• CAS: 96056-57-4
• 化学式: C₁₀H₁₈O₃
• 分子量: 186.251
• InChiKey: MEKGHNUFGFFHRE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  13
• 可旋转键数：
  6
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  43.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  ethyl 2-oxo-5,5-dimethylhexanoate 在 氢溴酸 、 溶剂黄146 作用下， 以 甲苯 为溶剂， 反应 1.25h， 生成 (Z)-2-[(2,2-Dimethyl-cyclopropanecarbonyl)-amino]-5,5-dimethyl-hex-2-enoic acid
  参考文献：
  名称：

  Inhibition of the mammalian .beta.-lactamase renal dipeptidase (dehydropeptidase-I) by Z-2-(acylamino)-3-substituted-propenoic acids

  摘要：

  The title enzyme deactivates the potent carbapenem antibiotic imipenem in the kidney, producing low antibiotic levels in the urinary tract. A series of (Z)-2-(acylamino)-3-substituted-propenoic acids (3) are specific, competitive inhibitors of the enzyme capable of increasing the urinary concentration of imipenem in vivo. Many of the compounds were prepared in one step from an alpha-keto acid and a primary amide. The optimum R2 groups are 2,2-dimethyl, -dichloro, and -dibromocyclopropyl. With R2 = 2,2-dimethylcyclopropyl (DMCP), a wide variety of R3 groups including alkyl, oxa- and thiaalkyl, and alkyl groups containing acidic, basic, and neutral substituents give effective inhibitors with Ki values of 0.02-1 microM and a range of pharmacokinetic properties. By resolution of enantiomers and X-ray crystallography, the enzyme-inhibitory activity of the DMCP group was found to reside with the 1S isomer. The cysteinyl compound 176 (cilastatin, MK-0791) has the desired pharmacological properties and has been chosen for combination with imipenem.

  DOI：

  10.1021/jm00389a018
• 作为产物：
  描述：

  2-(3,3-Dimethyl-butyl)-[1,3]dithiane-2-carboxylic acid ethyl ester 在 N-溴代丁二酰亚胺(NBS) 、 水 作用下， 以 乙腈 为溶剂， 反应 0.25h， 生成 ethyl 2-oxo-5,5-dimethylhexanoate
  参考文献：
  名称：

  Inhibition of the mammalian .beta.-lactamase renal dipeptidase (dehydropeptidase-I) by Z-2-(acylamino)-3-substituted-propenoic acids

  摘要：

  The title enzyme deactivates the potent carbapenem antibiotic imipenem in the kidney, producing low antibiotic levels in the urinary tract. A series of (Z)-2-(acylamino)-3-substituted-propenoic acids (3) are specific, competitive inhibitors of the enzyme capable of increasing the urinary concentration of imipenem in vivo. Many of the compounds were prepared in one step from an alpha-keto acid and a primary amide. The optimum R2 groups are 2,2-dimethyl, -dichloro, and -dibromocyclopropyl. With R2 = 2,2-dimethylcyclopropyl (DMCP), a wide variety of R3 groups including alkyl, oxa- and thiaalkyl, and alkyl groups containing acidic, basic, and neutral substituents give effective inhibitors with Ki values of 0.02-1 microM and a range of pharmacokinetic properties. By resolution of enantiomers and X-ray crystallography, the enzyme-inhibitory activity of the DMCP group was found to reside with the 1S isomer. The cysteinyl compound 176 (cilastatin, MK-0791) has the desired pharmacological properties and has been chosen for combination with imipenem.

  DOI：

  10.1021/jm00389a018

文献信息

• Fluoroketone enzyme inhibitors
  申请人：Becton, Dickinson and Company

  公开号：US05344952A1

  公开（公告）日：1994-09-06

  A method for enzyme immunoassay for a ligand suspected to be present in a liquid sample includes signal amplification by use of at least two enzymes and a blocked modulator for one of the enzymes. Ligand present in the liquid binds to an antiligand and an enzyme-labeled tracer. The resulting bound fraction is separated and the enzyme in the tracer removes the blocking group from the blocked modulator. The modulator activates or inhibits a second enzyme which catalyzes the conversion of a substrate to a product. The presence or absence of the ligand in the liquid is indicated by a signal, such as a color change or a rate of color change, associated with the product. The invention includes a new class of enzyme inhibitors and blocked inhibitors and a kit of materials useful for performing the method of the invention.

  一种用于酶免疫分析的方法，用于检测液体样品中可能存在的配体，包括利用至少两种酶和一个用于其中一种酶的阻断调节剂进行信号放大。液体中存在的配体与抗配体和标记酶的示踪剂结合。然后分离所得的结合分数，并且示踪剂中的酶去除阻断调节剂上的阻断基团。调节剂激活或抑制第二种酶，该酶催化底物转化为产物。液体中配体的存在或缺失由与产物相关的信号指示，例如颜色变化或颜色变化速率。该发明包括一类新型酶抑制剂和阻断抑制剂，以及用于执行该发明方法的一套有用材料。
• Total synthesis of the large non-ribosomal peptide polytheonamide B
  作者：Masayuki Inoue、Naoki Shinohara、Shintaro Tanabe、Tomoaki Takahashi、Ken Okura、Hiroaki Itoh、Yuki Mizoguchi、Maiko Iida、Nayoung Lee、Shigeru Matsuoka

  DOI：10.1038/nchem.554

  日期：2010.4

  Polytheonamide B is by far the largest non-ribosomal peptide known at present, and displays extraordinary cytotoxicity (EC50 = 68 pg ml−1, mouse leukaemia P388 cells). Its 48 amino-acid residues include a variety of non-proteinogenic d- and l-amino acids, and the absolute stereochemistry of these amino acids alternate in sequence. These structural features induce the formation of a stable β-strand-type structure, giving rise to an overall tubular structure over 30 Å in length. In a biological setting, this fold is believed to transport cations across the lipid bilayer through a pore, thereby acting as an ion channel. Here, we report the first chemical construction of polytheonamide B. Our synthesis relies on the combination of four key stages: syntheses of non-proteinogenic amino acids, a solid-phase assembly of four fragments of polytheonamide B, silver-mediated connection of the fragments and, finally, global deprotection. The synthetic material now available will allow studies of the relationships between its conformational properties, channel functions and cytotoxicity. Polytheonamide B is a large non-ribosomal peptide with very high bioactivity. The synthesis described here includes the first preparation of several non-proteinogenic amino acids and a general coupling strategy for large non-natural peptides. The synthesis is a key step necessary to understand and utilize the bioactivity of this and similar compounds.

  聚糖酰胺 B 是目前已知的最大的非核糖体肽，具有非凡的细胞毒性（EC50 = 68 pg mlâ1, 小鼠白血病 P388 细胞）。它的 48 个氨基酸残基包括多种非蛋白原性 d 和 l 氨基酸，这些氨基酸的绝对立体化学结构依次交替。这些结构特征促使形成稳定的δ-strand 型结构，从而形成长度超过 30 Ã 的整体管状结构。在生物环境中，这种折叠结构被认为可以通过一个孔隙在脂质双分子层中运输阳离子，从而起到离子通道的作用。在此，我们首次报告了聚神酰胺 B 的化学结构。我们的合成依赖于四个关键阶段的结合：非蛋白源氨基酸的合成、聚草酰胺 B 四个片段的固相组装、银介导的片段连接以及最后的全局脱保护。现在可用的合成材料将有助于研究其构象特性、通道功能和细胞毒性之间的关系。聚神酰胺 B 是一种大型非核糖体多肽，具有极高的生物活性。本文描述的合成包括首次制备几种非蛋白源氨基酸和大型非天然肽的一般偶联策略。该合成是了解和利用该化合物及类似化合物生物活性的关键一步。
• Signal enhancement in immunoassay by inhibition of enzymatic catalysis
  申请人：Becton Dickinson and Company

  公开号：EP0271731A2

  公开（公告）日：1988-06-22

  A method for enzyme immunoassay for a ligand suspected to be present in a liquid sample includes signal amplification by use of at least two enzymes and a blocked modulator for one of the enzymes. Ligand present in the liquid binds to an antiligand and an enzyme-labeled tracer. The resulting bound fraction is separated and the enzyme in the tracer removes the blocking group from the blocked modulator. The modulator activates or inhibits a second enzyme which catalyzes the conversion of a substrate to a product. The presence or absence of the ligand in the liquid is indicated by a signal, such as a color change or a rate of color change, associated with the product. The invention includes a new class of enzyme inhibitors and blocked inhibitors and a kit of materials useful for performing the method of the invention.

  一种对怀疑存在于液体样品中的配体进行酶免疫测定的方法，包括使用至少两种酶和其中一种酶的阻断调节剂进行信号放大。 液体中存在的配体与抗配体和酶标记的示踪剂结合。 由此产生的结合部分被分离，示踪剂中的酶从阻断调节剂中去除阻断基团。 调节剂激活或抑制第二种酶，该酶催化底物向产物的转化。 液体中配体的存在与否通过与产物相关的信号（如颜色变化或颜色变化率）来指示。 本发明包括一类新的酶抑制剂和阻断抑制剂，以及一套用于实施本发明方法的材料。
• Signal enhancement in assay for an enzyme
  申请人：Becton Dickinson and Company

  公开号：EP0354548A2

  公开（公告）日：1990-02-14

  A method for assay for an unknown enzyme suspected to be present in a liquid includes signal amplification by use of a second enzyme and a blocked modulator for the second enzyme. Unknown enzyme in the liquid removes a blocking group from the blocked modulator. The resulting modulator activates or inhibits the second enzyme which catalyzes an indicator reaction in which a substrate is converted to a product. The presence or absence of the unknown enzyme in the liquid is indicated by a signal, such as a color change or a rate of color change, associated with the indicator reaction. The concentration of the enzyme in the sample may be determined by the measurement of the signal. The invention includes a kit of materials useful for performing the method of the invention.

  一种检测液体中疑似存在的未知酶的方法，包括使用第二种酶和第二种酶的阻断调制剂进行信号放大。液体中的未知酶会从阻断调制剂中去除阻断基团。由此产生的调制剂激活或抑制第二种酶，第二种酶催化指示剂反应，其中底物转化为产物。液体中未知酶的存在与否可通过与指示剂反应相关的信号（如颜色变化或颜色变化率）来显示。样品中酶的浓度可通过测量信号来确定。本发明包括一套用于实施本发明方法的材料。
• Fluoroketones as blocked enzyme inhibitors for use in immunoassays
  申请人：Becton Dickinson and Company

  公开号：EP0501526A2

  公开（公告）日：1992-09-02

  A method for enzyme immunoassay for a ligand suspected to be present in a liquid sample includes signal amplification by use of at least two enzymes and a blocked modulator for one of the enzymes. Ligand present in the liquid binds to an antiligand and an enzyme-labeled tracer. The resulting bound fraction is separated and the enzyme in the tracer removes the blocking group from the blocked modulator. The modulator activates or inhibits a second enzyme which catalyzes the conversion of a substrate to a product. The presence or absence of the ligand in the liquid is indicated by a signal, such as a color change or a rate of color change, associated with the product. The invention includes a new class of enzyme inhibitors and blocked inhibitors and a kit of materials useful for performing the method of the invention.

  一种对液体样品中疑似存在的配体进行酶免疫测定的方法，包括使用至少两种酶和其中一种酶的阻断调节剂进行信号放大。液体中的配体与抗配体和酶标记的示踪剂结合。由此产生的结合部分被分离，示踪剂中的酶从阻断调制剂中去除阻断基团。调制剂激活或抑制第二种酶，该酶催化底物向产物的转化。液体中配体的存在与否可通过与产物相关的信号（如颜色变化或颜色变化率）来显示。本发明包括一类新的酶抑制剂和阻断抑制剂，以及用于实施本发明方法的材料试剂盒。