tert-butyl (3S) 1-[-12-[(3S) 3-((tert-butoxycarbonyl)amino)-2-oxo-azetidinyl]-12-oxo-6-dodecenoyl]-2-oxo-azetidinylcarbamate | 1445849-18-2

• 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: tert-butyl (3S) 1-[-12-[(3S) 3-((tert-butoxycarbonyl)amino)-2-oxo-azetidinyl]-12-oxo-6-dodecenoyl]-2-oxo-azetidinylcarbamate
• CAS: 1445849-18-2
• 化学式: C₂₈H₄₄N₄O₈
• 分子量: 564.679
• InChiKey: UCRKVOAVINTIJT-PMACEKPBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.19
• 重原子数：
  40.0
• 可旋转键数：
  12.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  151.42
• 氢给体数：
  2.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  6-heptenoyl chloride 、 tert-butyl (3S) 1-[-12-[(3S) 3-((tert-butoxycarbonyl)amino)-2-oxo-azetidinyl]-12-oxo-6-dodecenoyl]-2-oxo-azetidinylcarbamate 在 三氟乙酸 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以70%的产率得到N-{(3S)-1[-12-((3S)-3-(6-heptenoylamino)-2-oxoazetidinyl)12-oxo-6-dodecenoyl]-2-oxoazetidinyl}-6-heptenamide
  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：

  (S)-tert-butyl 1-hept-6-enoyl-2-oxoazetidin-3-ylcarbamate 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77%的产率得到tert-butyl (3S) 1-[-12-[(3S) 3-((tert-butoxycarbonyl)amino)-2-oxo-azetidinyl]-12-oxo-6-dodecenoyl]-2-oxo-azetidinylcarbamate
  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