p-nitrobenzyl 6α-bromo-2β-(nitrooxymethyl)-2α-methylpenam-3α-carboxylate 1-oxide | 95123-01-6

• 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: p-nitrobenzyl 6α-bromo-2β-(nitrooxymethyl)-2α-methylpenam-3α-carboxylate 1-oxide
• CAS: 95123-01-6
• 化学式: C₁₅H₁₄BrN₃O₉S
• 分子量: 492.261
• InChiKey: YVMRUSZAUMRMJE-AXOJJBJXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.67
• 重原子数：
  29.0
• 可旋转键数：
  7.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  159.19
• 氢给体数：
  0.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  p-nitrobenzyl 6α-bromo-2β-(nitrooxymethyl)-2α-methylpenam-3α-carboxylate 1-oxide 在 palladium on activated charcoal potassium permanganate 、 氢气 、 双氧水 、 碳酸氢钠 、 溶剂黄146 作用下， 以 水 、 乙酸乙酯 为溶剂， 反应 1.0h， 生成 (2S,3R,5R)-3-Hydroxymethyl-3-methyl-4,4,7-trioxo-4λ⁶-thia-1-aza-bicyclo[3.2.0]heptane-2-carboxylic acid
  参考文献：
  名称：

  Synthesis and .beta.-lactamase inhibitory properties of 2.beta.-[(acyloxy)methyl]-2.alpha.-methylpenam-3.alpha.-carboxylic acid 1,1-dioxides

  摘要：

  p-Nitrobenzyl 2 beta-[(benzoyloxy)methyl]-2 alpha-methylpenam-3 alpha-carboxylate was prepared by reaction of p-nitrobenzyl 2-[2-oxo-3 alpha-bromo-4-(benzothiazol-2-yldithio)azetidin-1-yl] -2-isopropenylacetate with silver benzoate in the presence of iodine. The resulting diester was oxidized to the sulfone with potassium permanganate and hydrogen peroxide, and the bromine and p-nitrobenzyl groups were removed by hydrogenolysis to give potassium 2 beta-(benzoyloxy)methyl 2 alpha-methylpenam-3 alpha-carboxylate 1,1-dioxide. A series of related compounds, including the pivaloyl, methoxybenzoyl, p-fluorobenzoyl, and p-aminobenzoyl derivatives, were prepared in a similar way. All of these compounds were potent beta-lactamase inhibitors in vitro against the TEM beta-lactamase from Klebsiella pneumoniae A22695 and Bacteroides fragiles A22695 but less active against the beta-lactamase from Staphylococcus aureus A9606. All compounds when administered orally in a 1:1 combination with amoxicillin did not show any significant protection of mice infected with S. aureus A9606. 2 beta-(Bromomethyl)-2 alpha-methylpenam-3 alpha-carboxylic acid was prepared and reacted with silver nitrate to give the nitrate ester. Oxidation with potassium permanganate and catalytic reduction afforded 2 beta-(hydroxymethyl)-2 alpha-methylpenam-3 alpha-carboxylic acid 1,1-dioxide. 2 beta-(Bromomethyl)-2 alpha-methylpenam-3 alpha-carboxylic acid 1,1-dioxide was found to be a strong beta-lactamase inhibitor, while the 2 beta-hydroxymethyl compound showed only weak beta-lactamase-inhibiting properties.

  DOI：

  10.1021/jm00382a025
• 作为产物：
  描述：

  p-nitrobenzyl 2-<2-oxo-3α-bromo-4-(benzothiazol-2-yldithio)azetidin-1-yl>-2-isopropenylacetate 在 乙酰胺 、 溴 、 silver nitrate 、 间氯过氧苯甲酸 作用下， 以 四氢呋喃 、 二氯甲烷 、 乙腈 为溶剂， 反应 18.0h， 生成 p-nitrobenzyl 6α-bromo-2β-(nitrooxymethyl)-2α-methylpenam-3α-carboxylate 1-oxide
  参考文献：
  名称：

  Synthesis and .beta.-lactamase inhibitory properties of 2.beta.-[(acyloxy)methyl]-2.alpha.-methylpenam-3.alpha.-carboxylic acid 1,1-dioxides

  摘要：

  p-Nitrobenzyl 2 beta-[(benzoyloxy)methyl]-2 alpha-methylpenam-3 alpha-carboxylate was prepared by reaction of p-nitrobenzyl 2-[2-oxo-3 alpha-bromo-4-(benzothiazol-2-yldithio)azetidin-1-yl] -2-isopropenylacetate with silver benzoate in the presence of iodine. The resulting diester was oxidized to the sulfone with potassium permanganate and hydrogen peroxide, and the bromine and p-nitrobenzyl groups were removed by hydrogenolysis to give potassium 2 beta-(benzoyloxy)methyl 2 alpha-methylpenam-3 alpha-carboxylate 1,1-dioxide. A series of related compounds, including the pivaloyl, methoxybenzoyl, p-fluorobenzoyl, and p-aminobenzoyl derivatives, were prepared in a similar way. All of these compounds were potent beta-lactamase inhibitors in vitro against the TEM beta-lactamase from Klebsiella pneumoniae A22695 and Bacteroides fragiles A22695 but less active against the beta-lactamase from Staphylococcus aureus A9606. All compounds when administered orally in a 1:1 combination with amoxicillin did not show any significant protection of mice infected with S. aureus A9606. 2 beta-(Bromomethyl)-2 alpha-methylpenam-3 alpha-carboxylic acid was prepared and reacted with silver nitrate to give the nitrate ester. Oxidation with potassium permanganate and catalytic reduction afforded 2 beta-(hydroxymethyl)-2 alpha-methylpenam-3 alpha-carboxylic acid 1,1-dioxide. 2 beta-(Bromomethyl)-2 alpha-methylpenam-3 alpha-carboxylic acid 1,1-dioxide was found to be a strong beta-lactamase inhibitor, while the 2 beta-hydroxymethyl compound showed only weak beta-lactamase-inhibiting properties.

  DOI：

  10.1021/jm00382a025