(12S,23S)-1,10,13,22-tetraazatricyclo[21.1.1.1^10,12]hexacosa-5,17-diene-2,9,11,14,21,24-hexaone | 1445849-25-1

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 大环内酰胺类
• 英文名称: (12S,23S)-1,10,13,22-tetraazatricyclo[21.1.1.1^10,12]hexacosa-5,17-diene-2,9,11,14,21,24-hexaone
• CAS: 1445849-25-1
• 化学式: C₂₂H₂₈N₄O₆
• 分子量: 444.488
• InChiKey: XAKKJJFAFFRONU-HOTGVXAUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.06
• 重原子数：
  32.0
• 可旋转键数：
  0.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  132.96
• 氢给体数：
  2.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  (12S,23S)-1,10,13,22-tetraazatricyclo[21.1.1.1^10,12]hexacosa-5,17-diene-2,9,11,14,21,24-hexaone 在 palladium 10% on activated carbon 、 氢气 作用下， 以 异丙醇 为溶剂， 反应 3.0h， 以60%的产率得到(12S,23S)-1,10,13,22-tetraazatricyclo[21.1.1.1^10,12]hexacosane-2,9,11,14,21,24-hexone
  参考文献：
  名称：

  Macrocycle-embedded β-lactams as novel inhibitors of the Penicillin Binding Protein PBP2a from MRSA

  摘要：

  Assuming that bicyclic beta-lactams endowed with high conformational adaptability should more easily form acyl-enzyme complexes with PBP2a than the traditional antibiotics, we have prepared a series of bis-2-oxo-azetidinyl macrocycles as potential inhibitors. The compounds are formally "head-head" (HH) cyclodimers of 1-(omega-alkenoyl)-3-(S)-(omega'-alkenoylamino)-2-azetidinones, with various lengths of the alkene chains, obtained by two successive metathesis reactions using the Grubbs catalyst. All compounds behave as acylating inhibitors of PBP2a and one beta-lactam (5c), embedded into the largest ring (32 atoms), features an activity close to that of Ceftobiprole. Conformational analyses, theoretical reactivity models and docking experiments in PBP2a cavity allow to propose a novel pharmacophore, i.e. the 3-(S)-acylamino-1-acyl-2-azetidinone ring, with the syn-conformation of the imide function, associated to a flexible macrocycle favoring the opening of the active site. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.03.052
• 作为产物：
  描述：

  N-{(3S)-1[-8-((3S)-3-(4-pentenoylamino)-2-oxoazetidinyl)-8-oxo-4-octenoyl]-2-oxoazetidinyl}-4-pentenamide 在 RuCl2(1,3-dimesityl-imidazolidin-2-yl)(PCy3)(=CHPh) 作用下， 以 二氯甲烷 为溶剂， 反应 4.0h， 以24%的产率得到(12S,23S)-1,10,13,22-tetraazatricyclo[21.1.1.1^10,12]hexacosa-5,17-diene-2,9,11,14,21,24-hexaone
  参考文献：
  名称：

  Macrocycle-embedded β-lactams as novel inhibitors of the Penicillin Binding Protein PBP2a from MRSA

  摘要：

  Assuming that bicyclic beta-lactams endowed with high conformational adaptability should more easily form acyl-enzyme complexes with PBP2a than the traditional antibiotics, we have prepared a series of bis-2-oxo-azetidinyl macrocycles as potential inhibitors. The compounds are formally "head-head" (HH) cyclodimers of 1-(omega-alkenoyl)-3-(S)-(omega'-alkenoylamino)-2-azetidinones, with various lengths of the alkene chains, obtained by two successive metathesis reactions using the Grubbs catalyst. All compounds behave as acylating inhibitors of PBP2a and one beta-lactam (5c), embedded into the largest ring (32 atoms), features an activity close to that of Ceftobiprole. Conformational analyses, theoretical reactivity models and docking experiments in PBP2a cavity allow to propose a novel pharmacophore, i.e. the 3-(S)-acylamino-1-acyl-2-azetidinone ring, with the syn-conformation of the imide function, associated to a flexible macrocycle favoring the opening of the active site. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.03.052