(3R,4R)-1-(pent-4-enoyl)-3-[1(R)-hydroxyethyl]-4-(acetoxy)-azetidin-2-one | 1157876-63-5

• 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: (3R,4R)-1-(pent-4-enoyl)-3-[1(R)-hydroxyethyl]-4-(acetoxy)-azetidin-2-one
• 英文别名: 1-(pent-4-enoyl)-(3R,4R)-3-[1(R)-hydroxyethyl]-4-(acetoxy)-azetidin-2-one；[(2R,3R)-3-[(1R)-1-hydroxyethyl]-4-oxo-1-pent-4-enoylazetidin-2-yl] acetate
• CAS: 1157876-63-5
• 化学式: C₁₂H₁₇NO₅
• 分子量: 255.271
• InChiKey: KTADTEZGLNTNIY-INNHCVQGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  18
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  83.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-戊烯酰氯 、 (3R,4R)-1-(pent-4-enoyl)-3-[1(R)-hydroxyethyl]-4-(acetoxy)-azetidin-2-one 在 吡啶 作用下， 以 二氯甲烷 为溶剂， 反应 15.0h， 以90%的产率得到(3R,4R)-1-(pent-4-enoyl)-3-[1(R)-(pent-4-enoyloxy)-ethyl]-4-(acetoxy)-azetidin-2-one
  参考文献：
  名称：

  β-Lactams Derived from a Carbapenem Chiron Are Selective Inhibitors of Human Fatty Acid Amide Hydrolase versus Human Monoacylglycerol Lipase

  摘要：

  A library of 30 beta-lactams has been prepared from (3R,4R)-3-[(R)-1'-(tbutyldimethylsilyloxy)-ethyl]-4-acetoxy-2-azetidinone, and the corresponding deacetoxy derivative, by sequential N- and O-functionalizations with various omega-alkenoyl and omega-arylalkanoyl chains. All compounds were selective inhibitors of hFAAH versus hMGL, and IC50 values in the nanomolar range (5-14 nM) were recorded for the best representatives. From time-dependent preincubation and rapid dilution studies, and from docking analyses in a homology model of the target enzyme, a reversible mechanism of inhibition of hFAAH is proposed.

  DOI：

  10.1021/jm9008532
• 作为产物：
  描述：

  1-(pent-4-enoyl)-(3R,4R)-3-[1(R)-(tert-butyldimethylsilyloxy)-ethyl]-4-(acetoxy)-azetidin-2-one 在 盐酸 、 溶剂黄146 作用下， 以 水 、 乙腈 为溶剂， 反应 3.0h， 以83%的产率得到(3R,4R)-1-(pent-4-enoyl)-3-[1(R)-hydroxyethyl]-4-(acetoxy)-azetidin-2-one
  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

• β-Lactams Derived from a Carbapenem Chiron Are Selective Inhibitors of Human Fatty Acid Amide Hydrolase versus Human Monoacylglycerol Lipase
  作者：Marion Feledziak、Catherine Michaux、Allan Urbach、Geoffray Labar、Giulio G. Muccioli、Didier M. Lambert、Jacqueline Marchand-Brynaert

  DOI：10.1021/jm9008532

  日期：2009.11.26

  A library of 30 beta-lactams has been prepared from (3R,4R)-3-[(R)-1'-(tbutyldimethylsilyloxy)-ethyl]-4-acetoxy-2-azetidinone, and the corresponding deacetoxy derivative, by sequential N- and O-functionalizations with various omega-alkenoyl and omega-arylalkanoyl chains. All compounds were selective inhibitors of hFAAH versus hMGL, and IC50 values in the nanomolar range (5-14 nM) were recorded for the best representatives. From time-dependent preincubation and rapid dilution studies, and from docking analyses in a homology model of the target enzyme, a reversible mechanism of inhibition of hFAAH is proposed.
• 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.