4-phenyl N-(4-methoxyphenylsulfonyloxy)-2-azetidinone

• 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: 4-phenyl N-(4-methoxyphenylsulfonyloxy)-2-azetidinone
• 英文别名: (2-Oxo-4-phenylazetidin-1-yl) 4-methoxybenzenesulfonate
• 化学式: C₁₆H₁₅NO₅S
• 分子量: 333.365
• InChiKey: ANSMEGYSOLGEEG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  81.3
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  4-phenyl O-Cbz-2-azetidinone 在 palladium on activated charcoal 氢气 、 三乙胺 作用下， 以 甲醇 、 乙腈 为溶剂， 反应 1.5h， 生成 4-phenyl N-(4-methoxyphenylsulfonyloxy)-2-azetidinone
  参考文献：
  名称：

  Potent mechanism-based inhibition of the TEM-1 .beta.-lactamase by novel N-sulfonyloxy .beta.-lactams

  摘要：

  A novel class of N-sulfonyloxy beta-lactam molecules are described as potent mechanism-based inactivators for the bacterial TEM-1 beta-lactamase, a prototypic class A enzyme. These molecules inactivate the enzyme with k(inact)/K-i values in the range of 1-7 x 10(4) M(-1) s(-1) and partition ratios (i.e., k(cat)/k(inact)) of 2-7. The mechanism of action of these inactivators was investigated. These molecules acylate the active-site serine of the TEM-1 beta-lactamase, a process that results in the release of the sulfonate attached to the lactam nitrogen, giving rise to a proposed beta-amino cinnamoyl derivative as the inhibitory species. This species undergoes gradual hydrolysis with concomitant recovery of activity, the rate constants for which were evaluated.

  DOI：

  10.1021/ja00127a005

文献信息

• Potent mechanism-based inhibition of the TEM-1 .beta.-lactamase by novel N-sulfonyloxy .beta.-lactams
  作者：Alexey Bulychev、Michael E. O'Brien、Irina Massova、Min Teng、Tracy A. Gibson、Marvin J. Miller、Shahriar Mobashery

  DOI：10.1021/ja00127a005

  日期：1995.6

  A novel class of N-sulfonyloxy beta-lactam molecules are described as potent mechanism-based inactivators for the bacterial TEM-1 beta-lactamase, a prototypic class A enzyme. These molecules inactivate the enzyme with k(inact)/K-i values in the range of 1-7 x 10(4) M(-1) s(-1) and partition ratios (i.e., k(cat)/k(inact)) of 2-7. The mechanism of action of these inactivators was investigated. These molecules acylate the active-site serine of the TEM-1 beta-lactamase, a process that results in the release of the sulfonate attached to the lactam nitrogen, giving rise to a proposed beta-amino cinnamoyl derivative as the inhibitory species. This species undergoes gradual hydrolysis with concomitant recovery of activity, the rate constants for which were evaluated.
• N-Sulfonyloxy-β-lactam Inhibitors for β-Lactamases
  作者：Alexey Bulychev、John R. Bellettini、Michael O'Brien、Peter J. Crocker、Jean-Pierre Samama、Marvin J. Miller、Shahriar Mobashery

  DOI：10.1016/s0040-4020(00)00427-0

  日期：2000.7

  Structure-function analysis with a series of N-sulfonyloxy beta-lactam molecules as inhibitors of beta-lactamases is reported. The best of these compounds acylate the active site of the class A TEM-1 beta-lactamase from Escherichia coli rapidly, and resist deacylation. Whereas acylation of the active site of the class C beta-lactamase from Enterobacter cloacae was not seen, these compounds function as competitive inhibitors of this enzyme. (C) 2000 Elsevier Science Ltd. All rights reserved.