6-epi-hetacillin | 3511-16-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 内酰胺类
• 英文名称: 6-epi-hetacillin
• 英文别名: 6α-((R)-2,2-dimethyl-5-oxo-4-phenyl-imidazolidin-1-yl)-penicillanic acid；markiertes 6-Epihetacillin；6-Epihetacilline；epihetacillin；(2S,5R,6S)-6-(2,2-dimethyl-5-oxo-4-phenylimidazolidin-1-yl)-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid
• CAS: 3511-16-8；10449-21-5；18715-92-9；34029-67-9；40439-01-8
• 化学式: C₁₉H₂₃N₃O₄S
• 分子量: 389.475
• InChiKey: DXVUYOAEDJXBPY-CMNLQMMWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.6
• 重原子数：
  27
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  115
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  6-epi-hetacillin 以 水 为溶剂， 反应 4.0h， 以32%的产率得到6-epi-ampicillin
  参考文献：
  名称：

  Chemical Reactivity of Penicillins and Cephalosporins. Intramolecular Involvement of the Acyl-Amido Side Chain

  摘要：

  The rate of degradation of B-epi-ampicillin in acidic, neutral, and alkaline aqueous solutions was followed at 35 degrees C and an ionic strength of 0.5 mol dm(-3) (KCl) by high-performance liquid chromatography (HPLC) and spectrophotometric assays. Pseudo-first-order rate constants were determined in a variety of buffer solutions, and the overall pH-rate profile was obtained by extrapolation to zero buffer concentration. The hydrolysis of 6-epi-ampicillin is subject to acid and hydroxide-ion catalysis and, for a penicillin, an unusual pH-independent reaction. Intramolecular general base-catalyzed hydrolysis by the side chain amido group is proposed to explain the enhanced rate of neutral hydrolysis of 6-epi-ampicillin and cephalosporins. The beta-lactam of 6-epi-ampicillin also undergoes intramolecular aminolysis by nucleophilic attack of the 6-alpha side chain amino group to give a stable piperazine-2,5-dione derivative. The low effective molarity for intramolecular aminolysis of only 40 M is partly attributed to the unfavorable trans to cis isomerization about the B-amide side chain required for ring closure. Theoretical calculations show that the intramolecular aminolysis of 6-epi-ampicillin nucleophilic attack occurs from the alpha-face of the beta-lactam ring with an activation energy of 14.4 kcal/mol.

  DOI：

  10.1021/jo981628j
• 作为产物：
  描述：

  hetacillin 在 sodium hydroxide 作用下， 反应 1.0h， 以92%的产率得到6-epi-hetacillin
  参考文献：
  名称：

  Chemical Reactivity of Penicillins and Cephalosporins. Intramolecular Involvement of the Acyl-Amido Side Chain

  摘要：

  The rate of degradation of B-epi-ampicillin in acidic, neutral, and alkaline aqueous solutions was followed at 35 degrees C and an ionic strength of 0.5 mol dm(-3) (KCl) by high-performance liquid chromatography (HPLC) and spectrophotometric assays. Pseudo-first-order rate constants were determined in a variety of buffer solutions, and the overall pH-rate profile was obtained by extrapolation to zero buffer concentration. The hydrolysis of 6-epi-ampicillin is subject to acid and hydroxide-ion catalysis and, for a penicillin, an unusual pH-independent reaction. Intramolecular general base-catalyzed hydrolysis by the side chain amido group is proposed to explain the enhanced rate of neutral hydrolysis of 6-epi-ampicillin and cephalosporins. The beta-lactam of 6-epi-ampicillin also undergoes intramolecular aminolysis by nucleophilic attack of the 6-alpha side chain amino group to give a stable piperazine-2,5-dione derivative. The low effective molarity for intramolecular aminolysis of only 40 M is partly attributed to the unfavorable trans to cis isomerization about the B-amide side chain required for ring closure. Theoretical calculations show that the intramolecular aminolysis of 6-epi-ampicillin nucleophilic attack occurs from the alpha-face of the beta-lactam ring with an activation energy of 14.4 kcal/mol.

  DOI：

  10.1021/jo981628j

文献信息

• Chemical Reactivity of Penicillins and Cephalosporins. Intramolecular Involvement of the Acyl-Amido Side Chain
  作者：Antonio Llinás、Bartolomé Vilanova、Juan Frau、Francisco Muñoz、Josefa Donoso、Michael I. Page

  DOI：10.1021/jo981628j

  日期：1998.11.1

  The rate of degradation of B-epi-ampicillin in acidic, neutral, and alkaline aqueous solutions was followed at 35 degrees C and an ionic strength of 0.5 mol dm(-3) (KCl) by high-performance liquid chromatography (HPLC) and spectrophotometric assays. Pseudo-first-order rate constants were determined in a variety of buffer solutions, and the overall pH-rate profile was obtained by extrapolation to zero buffer concentration. The hydrolysis of 6-epi-ampicillin is subject to acid and hydroxide-ion catalysis and, for a penicillin, an unusual pH-independent reaction. Intramolecular general base-catalyzed hydrolysis by the side chain amido group is proposed to explain the enhanced rate of neutral hydrolysis of 6-epi-ampicillin and cephalosporins. The beta-lactam of 6-epi-ampicillin also undergoes intramolecular aminolysis by nucleophilic attack of the 6-alpha side chain amino group to give a stable piperazine-2,5-dione derivative. The low effective molarity for intramolecular aminolysis of only 40 M is partly attributed to the unfavorable trans to cis isomerization about the B-amide side chain required for ring closure. Theoretical calculations show that the intramolecular aminolysis of 6-epi-ampicillin nucleophilic attack occurs from the alpha-face of the beta-lactam ring with an activation energy of 14.4 kcal/mol.