benzyl (1S,4S,5S)-6-(tert-butyldimethylsilanyl)-4-(tetrahydropyran-2-yloxy)-7-oxo-2,6-diazabicyclo<3.2.0>heptane-2-carboxylate | 214837-33-9

• 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: benzyl (1S,4S,5S)-6-(tert-butyldimethylsilanyl)-4-(tetrahydropyran-2-yloxy)-7-oxo-2,6-diazabicyclo<3.2.0>heptane-2-carboxylate
• CAS: 214837-33-9
• 化学式: C₂₄H₃₆N₂O₅Si
• 分子量: 460.646
• InChiKey: RDLBELDKKOOVRE-ISUXGXDNSA-N

物化性质

• 沸点：
  544.1±50.0 °C(Predicted)
• 密度：
  1.17±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.14
• 重原子数：
  32.0
• 可旋转键数：
  5.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  68.31
• 氢给体数：
  0.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  benzyl (1S,4S,5S)-6-(tert-butyldimethylsilanyl)-4-(tetrahydropyran-2-yloxy)-7-oxo-2,6-diazabicyclo<3.2.0>heptane-2-carboxylate 在 4-甲基苯磺酸吡啶 作用下， 以 甲醇 为溶剂， 反应 24.0h， 以65%的产率得到benzyl (1S,4S,5S)-6-(tert-butyldimethylsilanyl)-4-hydroxy-7-oxo-2,6-diazabicyclo<3.2.0>heptane-2-carboxylate
  参考文献：
  名称：

  Structure-Based Design of β-Lactamase Inhibitors. 1. Synthesis and Evaluation of Bridged Monobactams

  摘要：

  Bridged monobactams are novel, potent, mechanism-based inhibitors of class C beta-lactamases, designed using X-ray crystal structures of the enzymes. They stabilize the acyl-enzyme intermediate by blocking access of water to the enzyme-inhibitor ester bond. Bridged monobactams are selective class C beta-lactamase inhibitors, with half-inhibition constants as low as 10 nM, and are less effective against class A and class B enzymes (half-inhibition constants > 100 mu M) because of the different hydrolysis mechanisms in these classes of beta-lactamases. The stability of the acyl-enzyme complexes formed with class C beta-lactamases (half-lives up to 2 days were observed) enabled determination of their crystal structures. The conformation of the inhibitor moiety was close to that predicted by molecular modeling, confirming a simple reaction mechanism, unlike those of known beta-lactamase inhibitors such as clavulanic acid and penam sulfones, which involve secondary rearrangements. Synergy between the bridged monobactams and beta-lactamase-labile antibiotics could be observed when such combinations were tested against strains of Enterobacteriaceae that produce large amounts of class C beta-lactamases. The minimal inhibitory concentration of the antibiotic of more than 64 mg/L could be decreased to 0.25 mg/L in a 1:4 combination with the inhibitor.

  DOI：

  10.1021/jm980023c
• 作为产物：
  描述：

  [(2S,3S)-2-((R)-1,2-Dihydroxy-ethyl)-1-(3,4-dimethoxy-benzyl)-4-oxo-azetidin-3-yl]-carbamic acid benzyl ester 在 dipotassium peroxodisulfate 、 四丁基溴化铵 、 碳酸氢钠 、 对甲苯磺酸 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 57.0h， 生成 benzyl (1S,4S,5S)-6-(tert-butyldimethylsilanyl)-4-(tetrahydropyran-2-yloxy)-7-oxo-2,6-diazabicyclo<3.2.0>heptane-2-carboxylate
  参考文献：
  名称：

  Structure-Based Design of β-Lactamase Inhibitors. 1. Synthesis and Evaluation of Bridged Monobactams

  摘要：

  Bridged monobactams are novel, potent, mechanism-based inhibitors of class C beta-lactamases, designed using X-ray crystal structures of the enzymes. They stabilize the acyl-enzyme intermediate by blocking access of water to the enzyme-inhibitor ester bond. Bridged monobactams are selective class C beta-lactamase inhibitors, with half-inhibition constants as low as 10 nM, and are less effective against class A and class B enzymes (half-inhibition constants > 100 mu M) because of the different hydrolysis mechanisms in these classes of beta-lactamases. The stability of the acyl-enzyme complexes formed with class C beta-lactamases (half-lives up to 2 days were observed) enabled determination of their crystal structures. The conformation of the inhibitor moiety was close to that predicted by molecular modeling, confirming a simple reaction mechanism, unlike those of known beta-lactamase inhibitors such as clavulanic acid and penam sulfones, which involve secondary rearrangements. Synergy between the bridged monobactams and beta-lactamase-labile antibiotics could be observed when such combinations were tested against strains of Enterobacteriaceae that produce large amounts of class C beta-lactamases. The minimal inhibitory concentration of the antibiotic of more than 64 mg/L could be decreased to 0.25 mg/L in a 1:4 combination with the inhibitor.

  DOI：

  10.1021/jm980023c