(R)-2-[3,5-di(N,N-dimethylcarbamyloxy)phenyl]oxirane | 1050279-04-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (R)-2-[3,5-di(N,N-dimethylcarbamyloxy)phenyl]oxirane
• 英文别名: (R)-[3,5-bis(dimethylcarbamoyloxy)phenyl]oxirane；[3-(dimethylcarbamoyloxy)-5-[(2R)-oxiran-2-yl]phenyl] N,N-dimethylcarbamate
• CAS: 1050279-04-3
• 化学式: C₁₄H₁₈N₂O₅
• 分子量: 294.307
• InChiKey: KHCRMINTBUGOAT-LBPRGKRZSA-N

物化性质

• 沸点：
  417.6±45.0 °C(Predicted)
• 密度：
  1.272±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  71.6
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (R)-2-[3,5-di(N,N-dimethylcarbamyloxy)phenyl]oxirane 、 异丙胺 在 盐酸 作用下， 以 水 、 异丙醇 为溶剂， 以80%的产率得到(R)-3,5-bis(N,N-dimethylcarbamyloxy)metaproterenol
  参考文献：
  名称：

  Metaproterenol, Isoproterenol, and Their Bisdimethylcarbamate Derivatives as Human Cholinesterase Inhibitors

  摘要：

  Metaproterenol and isoproterenol are bronchodilators that provide a structural basis for many other bronchodilators currently in use. One of these structurally related bronchodilators is terbutaline; it is administered as a prodrug, bambuterol, and is metabolized (bioconverted) into terbutaline by butyrylcholinesterase (BChE). The metabolism rate can be affected by BChE gene polymorphism in the human population and BChE stereoselectivity. The aim of our study was to investigate inhibition of human BChE and acetylcholinesterase (AChE) with metaproterenol, isoproterenol, and newly synthesized racemic bisdimethylcarbamate derivatives of metaproterenol (metacarb) and isoproterenol (isocarb) and their (R)-enantiomers to see if their bioconversion is affected by BChE inhibition in the same way as that for bambuterol. Metacarb and isocarb proved to be selective BChE inhibitors, as they progressively inhibited AChE 960 to 80 times more slowly than BChE(UU). All studied cholinesterases displayed poor affinity for metaproterenol and isoproterenol, yet BChE(UU) had an affinity about five times higher than that of AChE.

  DOI：

  10.1021/jm300289k
• 作为产物：
  描述：

  3,5-二乙酰氧基苯乙酮 在 溴 、 potassium carbonate 、 sodium chloride 、 sodium hydroxide 作用下， 以 四氢呋喃 、 aq. phosphate buffer 、 乙醇 、 水 、 溶剂黄146 、 N,N-二甲基甲酰胺 、 异丙醇 、 甘油 、 乙腈 为溶剂， 反应 155.34h， 生成 (R)-2-[3,5-di(N,N-dimethylcarbamyloxy)phenyl]oxirane
  参考文献：
  名称：

  Synthesis of (R)-bambuterol based on asymmetric reduction of 1-[3,5-bis(dimethylcarbamoyloxy)phenyl]-2-chloroethanone with incubated whole cells of Williopsis californica JCM 3600

  摘要：

  To achieve the synthesis of (R)-bambuterol, a prodrug of (R)-terbutaline, asymmetric reduction of 1-[3,5-bis(dimethylcarbamoyloxy)phenyl]-2-chloroethanone with whole cells of Williopsis californica JCM 3600 pre-incubated on glycerol as a carbon source was examined. Initially, the insolubility of this crystalline substrate (mp 126-127 degrees C) in the incubation broth was an obstacle that needed to be overcome. To solve the problem, the concentration of glycerol was increased to 10% during reduction. Glycerol worked well for recycling oxido-reduction cofactors and for enhancing the water solubility of the substrate. The reduction proceeded smoothly to give enantiomerically pure (R)-alcohol in 81% isolated yield. (C) 2013 Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.molcatb.2013.08.003

文献信息

• Synthesis of (R)-bambuterol based on asymmetric reduction of 1-[3,5-bis(dimethylcarbamoyloxy)phenyl]-2-chloroethanone with incubated whole cells of Williopsis californica JCM 3600
  作者：Kento Asami、Takuya Machida、Sonna Jung、Kengo Hanaya、Mitsuru Shoji、Takeshi Sugai

  DOI：10.1016/j.molcatb.2013.08.003

  日期：2013.12

  To achieve the synthesis of (R)-bambuterol, a prodrug of (R)-terbutaline, asymmetric reduction of 1-[3,5-bis(dimethylcarbamoyloxy)phenyl]-2-chloroethanone with whole cells of Williopsis californica JCM 3600 pre-incubated on glycerol as a carbon source was examined. Initially, the insolubility of this crystalline substrate (mp 126-127 degrees C) in the incubation broth was an obstacle that needed to be overcome. To solve the problem, the concentration of glycerol was increased to 10% during reduction. Glycerol worked well for recycling oxido-reduction cofactors and for enhancing the water solubility of the substrate. The reduction proceeded smoothly to give enantiomerically pure (R)-alcohol in 81% isolated yield. (C) 2013 Elsevier B.V. All rights reserved.
• Metaproterenol, Isoproterenol, and Their Bisdimethylcarbamate Derivatives as Human Cholinesterase Inhibitors
  作者：Anita Bosak、Ivana Gazić Smilović、Goran Šinko、Vladimir Vinković、Zrinka Kovarik

  DOI：10.1021/jm300289k

  日期：2012.8.9

  Metaproterenol and isoproterenol are bronchodilators that provide a structural basis for many other bronchodilators currently in use. One of these structurally related bronchodilators is terbutaline; it is administered as a prodrug, bambuterol, and is metabolized (bioconverted) into terbutaline by butyrylcholinesterase (BChE). The metabolism rate can be affected by BChE gene polymorphism in the human population and BChE stereoselectivity. The aim of our study was to investigate inhibition of human BChE and acetylcholinesterase (AChE) with metaproterenol, isoproterenol, and newly synthesized racemic bisdimethylcarbamate derivatives of metaproterenol (metacarb) and isoproterenol (isocarb) and their (R)-enantiomers to see if their bioconversion is affected by BChE inhibition in the same way as that for bambuterol. Metacarb and isocarb proved to be selective BChE inhibitors, as they progressively inhibited AChE 960 to 80 times more slowly than BChE(UU). All studied cholinesterases displayed poor affinity for metaproterenol and isoproterenol, yet BChE(UU) had an affinity about five times higher than that of AChE.