(5R)-6c-((R)-1-hydroxy-ethyl)-3,3-dimethyl-7-oxo-(5rH)-4-thia-1-aza-bicyclo[3.2.0]heptane-2c-carboxylic acid | 62263-74-5

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (5R)-6c-((R)-1-hydroxy-ethyl)-3,3-dimethyl-7-oxo-(5rH)-4-thia-1-aza-bicyclo[3.2.0]heptane-2c-carboxylic acid
• 英文别名: (2S,5R,6S)-6-[(1R)-1-hydroxyethyl]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid
• CAS: 62263-74-5
• 化学式: C₁₀H₁₅NO₄S
• 分子量: 245.299
• InChiKey: MPTLCUDUQPXSPL-FZGKIIIMSA-N

物化性质

• 沸点：
  482.9±45.0 °C(Predicted)
• 密度：
  1.44±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  103
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  4-Nitrobenzyl 6,6-dibromopenicillanate 在 palladium on activated charcoal 偶氮二异丁腈 、 甲基溴化镁 、 氢气 、 三正丁基氢锡 作用下， 生成 (5R)-6c-((R)-1-hydroxy-ethyl)-3,3-dimethyl-7-oxo-(5rH)-4-thia-1-aza-bicyclo[3.2.0]heptane-2c-carboxylic acid
  参考文献：
  名称：

  Quantification of the extent of attenuation of the rate of turnover chemistry of the TEM-1 β-lactamase by the α-1R-hydroxyethyl group in substrates

  摘要：

  The 6 alpha-1R-hydroxyethyl group of imipenem, a clinically used carbapenem antibacterial agent, is believed to displace the hydrolytic water from its optimal position in the active site of class A beta-lactamases. This interaction renders the molecule a poor substrate for these bacterial enzymes, hence preserving the antibacterial property of the antibiotic. The extent of the contribution of the 6 alpha-1R-hydroxyethyl group in substrates toward stabilization of the antibiotic to the hydrolytic action of class A TEM-1 beta-lactamase was studied by the synthesis and evaluation of two penicillanic acid derivatives, 6 alpha-(1R-hydroxyethyl)penicillanic acid (2) and 6 beta-(1R-hydroxyethyl)penicillanic acid (3). The kinetic evaluation of the enzymic hydrolysis of these two penicillanic acid derivatives indicated that the 6 alpha-1R-hydroxyethyl group imparts as much as 10(4)-fold to the hydrolytic stability of the beta-lactam substrate.

  DOI：

  10.1016/0960-894x(96)00022-4

文献信息

• Quantification of the extent of attenuation of the rate of turnover chemistry of the TEM-1 β-lactamase by the α-1R-hydroxyethyl group in substrates
  作者：Kazuyuki Miyashita、Irina Massova、Shahriar Mobashery

  DOI：10.1016/0960-894x(96)00022-4

  日期：1996.2

  The 6 alpha-1R-hydroxyethyl group of imipenem, a clinically used carbapenem antibacterial agent, is believed to displace the hydrolytic water from its optimal position in the active site of class A beta-lactamases. This interaction renders the molecule a poor substrate for these bacterial enzymes, hence preserving the antibacterial property of the antibiotic. The extent of the contribution of the 6 alpha-1R-hydroxyethyl group in substrates toward stabilization of the antibiotic to the hydrolytic action of class A TEM-1 beta-lactamase was studied by the synthesis and evaluation of two penicillanic acid derivatives, 6 alpha-(1R-hydroxyethyl)penicillanic acid (2) and 6 beta-(1R-hydroxyethyl)penicillanic acid (3). The kinetic evaluation of the enzymic hydrolysis of these two penicillanic acid derivatives indicated that the 6 alpha-1R-hydroxyethyl group imparts as much as 10(4)-fold to the hydrolytic stability of the beta-lactam substrate.