4-Thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid,6-[(acetyloxy)(6,7-dihydro-4H-thieno[3,2-c]pyran-2-yl)methyl]-6-bromo-7-oxo-, (4-nitrophenyl)methyl ester, (5R)- | 623906-34-3

• 分子结构分类: 有机化合物 - 有机杂环化合物
• 英文名称: 4-Thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid,6-[(acetyloxy)(6,7-dihydro-4H-thieno[3,2-c]pyran-2-yl)methyl]-6-bromo-7-oxo-, (4-nitrophenyl)methyl ester, (5R)-
• CAS: 623906-34-3
• 化学式: C₂₃H₁₉BrN₂O₈S₂
• 分子量: 595.448
• InChiKey: DAHGVARRVOJDFB-RUDSSYLZSA-N

物化性质

• 沸点：
  778.2±60.0 °C(Predicted)
• 密度：
  1.73±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.97
• 重原子数：
  36.0
• 可旋转键数：
  7.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  125.28
• 氢给体数：
  0.0
• 氢受体数：
  10.0

反应信息

• 作为反应物：
  描述：

  4-Thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid,6-[(acetyloxy)(6,7-dihydro-4H-thieno[3,2-c]pyran-2-yl)methyl]-6-bromo-7-oxo-, (4-nitrophenyl)methyl ester, (5R)- 在 palladium on activated charcoal phosphate buffer 、 氢气 、 sodium hydroxide 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 以38%的产率得到6-(6,7-dihydro-4H-thieno[3,2-c]pyran-2-ylmethylene)-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid sodium salt
  参考文献：
  名称：

  Structure-Activity Relationship of 6-Methylidene Penems Bearing 6,5 Bicyclic Heterocycles as Broad-Spectrum β-Lactamase Inhibitors:  Evidence for 1,4-Thiazepine Intermediates with C7 R Stereochemistry by Computational Methods

  摘要：

  The design and synthesis of a series of 6-methylidene penems containing [6,5]-fused bicycles (thiophene, imidazole, or pyrazle-fused system) as novel class A, B, and C beta-lactamase inhibitors is described. These penems proved to be potent inhibitors of the TEM-1 (class A) and AmpC (class C) beta-lactamases and less so against the class B metallo-beta-lactamase CcrA. Their in vitro and in vivo activities in combination with piperacillin are discussed. On the basis of the crystallographic structures of a serine-bound reaction intermediate of 2 with SHV-1 (class A) and GC1 (class C) enzymes, compounds 14a-1 were designed and synthesized. Penems are proposed to form a seven-membered 1,4 thiazepine ring in both class A and C beta-lactamases. The interaction energy calculation for the enzyme-bound intermediates favor the formation of the C7 R enantiomer over the S enantiomer of the 1,4-thiazepine in both beta-lactamases, which is consistent with those obtained from the crystal structure of 2 with SHV-1 and GC1.

  DOI：

  10.1021/jm060021p
• 作为产物：
  描述：

  吡喃-4-酮 在 manganese(IV) oxide 、 lithium aluminium tetrahydride 、 三乙胺 、 magnesium bromide 、 三氯氧磷 作用下， 以 四氢呋喃 、 二氯甲烷 、 乙腈 为溶剂， 反应 65.0h， 生成 4-Thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid,6-[(acetyloxy)(6,7-dihydro-4H-thieno[3,2-c]pyran-2-yl)methyl]-6-bromo-7-oxo-, (4-nitrophenyl)methyl ester, (5R)-
  参考文献：
  名称：

  Structure-Activity Relationship of 6-Methylidene Penems Bearing 6,5 Bicyclic Heterocycles as Broad-Spectrum β-Lactamase Inhibitors:  Evidence for 1,4-Thiazepine Intermediates with C7 R Stereochemistry by Computational Methods

  摘要：

  The design and synthesis of a series of 6-methylidene penems containing [6,5]-fused bicycles (thiophene, imidazole, or pyrazle-fused system) as novel class A, B, and C beta-lactamase inhibitors is described. These penems proved to be potent inhibitors of the TEM-1 (class A) and AmpC (class C) beta-lactamases and less so against the class B metallo-beta-lactamase CcrA. Their in vitro and in vivo activities in combination with piperacillin are discussed. On the basis of the crystallographic structures of a serine-bound reaction intermediate of 2 with SHV-1 (class A) and GC1 (class C) enzymes, compounds 14a-1 were designed and synthesized. Penems are proposed to form a seven-membered 1,4 thiazepine ring in both class A and C beta-lactamases. The interaction energy calculation for the enzyme-bound intermediates favor the formation of the C7 R enantiomer over the S enantiomer of the 1,4-thiazepine in both beta-lactamases, which is consistent with those obtained from the crystal structure of 2 with SHV-1 and GC1.

  DOI：

  10.1021/jm060021p