(1S,6R)-7-(3,4-dimethoxybenzyl)-8-oxo-2,7-diazabicyclo<4.2.0>octane-2-carboxylic acid tert-butyl ester | 214837-41-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (1S,6R)-7-(3,4-dimethoxybenzyl)-8-oxo-2,7-diazabicyclo<4.2.0>octane-2-carboxylic acid tert-butyl ester
• CAS: 214837-41-9
• 化学式: C₂₀H₂₈N₂O₅
• 分子量: 376.453
• InChiKey: JBETWOVCIXKJDQ-PBHICJAKSA-N

物化性质

• 沸点：
  531.698±50.00 °C(Press: 760.00 Torr)(predicted)
• 密度：
  1.195±0.06 g/cm3(Temp: 25 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.81
• 重原子数：
  27.0
• 可旋转键数：
  4.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.6
• 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：

  (1S,6R)-7-(3,4-dimethoxybenzyl)-8-oxo-2,7-diazabicyclo<4.2.0>octane-2-carboxylic acid tert-butyl ester 在 dipotassium peroxodisulfate 、 碳酸氢钠 作用下， 以 水 、 乙腈 为溶剂， 以55%的产率得到tert-butyl (1S,6R)-8-oxo-2,7-diazabicyclo<4.2.0>octane-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：

  (3S,4S)-<1-(3,4-dimethoxybenzyl)-2-<3-(methylsulfonyloxy)propyl>-4-oxoazetidin-3-yl>carbamic acid tert-butyl ester 在 sodium hydride 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 以87%的产率得到(1S,6R)-7-(3,4-dimethoxybenzyl)-8-oxo-2,7-diazabicyclo<4.2.0>octane-2-carboxylic acid tert-butyl ester
  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