(2S,5R,6S)-6-Bromo-6-((R)-1-hydroxy-ethyl)-3,3-dimethyl-7-oxo-4-thia-1-aza-bicyclo[3.2.0]heptane-2-carboxylic acid 4-nitro-benzyl ester | 174231-05-1

• 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: (2S,5R,6S)-6-Bromo-6-((R)-1-hydroxy-ethyl)-3,3-dimethyl-7-oxo-4-thia-1-aza-bicyclo[3.2.0]heptane-2-carboxylic acid 4-nitro-benzyl ester
• CAS: 174231-05-1
• 化学式: C₁₇H₁₉BrN₂O₆S
• 分子量: 459.318
• InChiKey: SCQLAXOHVRUBFZ-JOGDPCBZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.21
• 重原子数：
  27.0
• 可旋转键数：
  5.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  109.98
• 氢给体数：
  1.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  (2S,5R,6S)-6-Bromo-6-((R)-1-hydroxy-ethyl)-3,3-dimethyl-7-oxo-4-thia-1-aza-bicyclo[3.2.0]heptane-2-carboxylic acid 4-nitro-benzyl ester 在 palladium on activated charcoal 偶氮二异丁腈 、 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
• 作为产物：
  描述：

  4-Nitrobenzyl 6,6-dibromopenicillanate 、 乙醛 在 甲基溴化镁 作用下， 以37%的产率得到(2S,5R,6S)-6-Bromo-6-((R)-1-hydroxy-ethyl)-3,3-dimethyl-7-oxo-4-thia-1-aza-bicyclo[3.2.0]heptane-2-carboxylic acid 4-nitro-benzyl ester
  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

• Stereoselective Reduction of α-Bromopenicillanates by Tributylphosphine
  作者：Akihiro Ishiwata、Lakshmi P. Kotra、Kazuyuki Miyashita、Tsuyoshi Nagase、Shahriar Mobashery

  DOI：10.1021/ol000185e

  日期：2000.9.1

  [reaction: see text] Diastereoselective reduction of 6-bromo-6-substituted penicillanate esters has been achieved by treatment with tributylphosphine to give 6-substituted penicillanate esters. This reaction would appear to proceed through a phosphonium beta-lactam enolate species, followed by a diastereoselective protonation. This method has the advantage of being simple to carry out and it is mild

  [反应：见正文]通过用三丁基膦处理得到6-取代的青霉酸酯，已经实现了6-溴-6-取代的青霉酸酯的非对映选择性还原。该反应似乎通过through-β-内酰胺烯醇化species物种进行，随后是非对映选择性质子化。该方法的优点是易于实施，并且温和，非对映选择性高，并且应能耐受底物中的许多官能团。这些意见的含义进行了讨论。