(11R,12R,14R)-14-acetoxy-11-methyl-2,9,13-trioxo-10-oxa-1-aza-bicyclo[10.1.1]tetradecane | 1157876-67-9

• 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: (11R,12R,14R)-14-acetoxy-11-methyl-2,9,13-trioxo-10-oxa-1-aza-bicyclo[10.1.1]tetradecane
• 英文别名: [(11R,12R,13R)-11-methyl-2,9,14-trioxo-10-oxa-1-azabicyclo[10.1.1]tetradecan-13-yl] acetate
• CAS: 1157876-67-9
• 化学式: C₁₅H₂₁NO₆
• 分子量: 311.335
• InChiKey: PSVJQVPWZKZUQP-ZDBHGNHJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  90
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  (E,11R,12R,14R)-14-acetoxy-11-methyl-2,9,13-trioxo-10-oxa-1-aza-bicyclo[10.1.1]tetradec-5-ene 在 palladium on carbon 、 氢气 作用下， 以 乙酸乙酯 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 17.0h， 以100%的产率得到(11R,12R,14R)-14-acetoxy-11-methyl-2,9,13-trioxo-10-oxa-1-aza-bicyclo[10.1.1]tetradecane
  参考文献：
  名称：

  Large ring 1,3-bridged 2-azetidinones: Experimental and theoretical studies

  摘要：

  The relationship between angular strain and (re)activity of bicyclic 2-azetidinones is still an open question of major concern in the field of penicillin antibiotics. Our study deals with original 13-membered-ring 1,3-bridged 2-azetidinones related to the carbapenem family, and featuring a "planar amide" instead of the "twisted amide" typical of penam derivatives. The bicycles 11 and 12 were obtained from acetoxy-azetidinone 7, via the key-intermediate 10, by using the RCM (ring closing metathesis) strategy. Theoretical predictions and experimental results of hydrolysis showed that the large bicycle 12, endowed with high conformational flexibility, is more reactive than the bicycle 11, including a C=C bond of E configuration, and the monocyclic 2-azetidinone precursor 10. The processing of 2-azetidinones 10-12 in the active site of serine enzymes has been computed by ab initio methods, considering three models. Due to geometrical parameters of the enzymic cavity (nucleophilic attack from the alpha-face), precursor 10 was predicted more active than 11 and 12 in the acylation step by Ser-OH. Indeed, bicycles 11 and 12 are modest inhibitors of PBP2a, while 10 is a good to excellent inhibitor of PBP2a and R39 bacterial enzymes. (C) 2008 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2008.10.016

文献信息

• Large ring 1,3-bridged 2-azetidinones: Experimental and theoretical studies
  作者：Allan Urbach、Georges Dive、Bernard Tinant、Valérie Duval、Jacqueline Marchand-Brynaert

  DOI：10.1016/j.ejmech.2008.10.016

  日期：2009.5

  The relationship between angular strain and (re)activity of bicyclic 2-azetidinones is still an open question of major concern in the field of penicillin antibiotics. Our study deals with original 13-membered-ring 1,3-bridged 2-azetidinones related to the carbapenem family, and featuring a "planar amide" instead of the "twisted amide" typical of penam derivatives. The bicycles 11 and 12 were obtained from acetoxy-azetidinone 7, via the key-intermediate 10, by using the RCM (ring closing metathesis) strategy. Theoretical predictions and experimental results of hydrolysis showed that the large bicycle 12, endowed with high conformational flexibility, is more reactive than the bicycle 11, including a C=C bond of E configuration, and the monocyclic 2-azetidinone precursor 10. The processing of 2-azetidinones 10-12 in the active site of serine enzymes has been computed by ab initio methods, considering three models. Due to geometrical parameters of the enzymic cavity (nucleophilic attack from the alpha-face), precursor 10 was predicted more active than 11 and 12 in the acylation step by Ser-OH. Indeed, bicycles 11 and 12 are modest inhibitors of PBP2a, while 10 is a good to excellent inhibitor of PBP2a and R39 bacterial enzymes. (C) 2008 Elsevier Masson SAS. All rights reserved.