(2S)-2-[(2,6-dimethylphenoxy)methyl]oxirane

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: (2S)-2-[(2,6-dimethylphenoxy)methyl]oxirane
• 化学式: C₁₁H₁₄O₂
• 分子量: 178.231
• InChiKey: VHWHISLSSKROOL-JTQLQIEISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  13
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  21.8
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (2S)-2-[(2,6-dimethylphenoxy)methyl]oxirane 在 palladium 10% on activated carbon 、 氢气 、 lithium bromide 作用下， 以 甲醇 为溶剂， 20.0 ℃ 、344.75 kPa 条件下， 反应 6.0h， 生成 L-美西律
  参考文献：
  名称：

  Chiral aziridine ring opening: facile synthesis of (R)-mexiletine and (R)-phenoxybenzamine hydrochloride

  摘要：

  A simple and efficient synthesis of chiral drugs (R)-mexiletine 1, an anti-arrhythmic drug and (R)-phenoxybenzamine hydrochloride 2, an anti-hypertensive drug has been described via controlled reductive ring opening of chiral aziridine as a key step. The target compounds 1 and 2 were obtained in overall yields of 34% and 10.5%, respectively. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2015.07.032
• 作为产物：
  描述：

  2-[(2,6-二甲基苯氧基)甲基]环氧乙烷 在 (R,R)-Jacobsen catalyst 、 水 作用下， 反应 30.0h， 以43%的产率得到(2S)-2-[(2,6-dimethylphenoxy)methyl]oxirane
  参考文献：
  名称：

  水解动力学拆分法方便地合成对映体纯的（R）-美西律

  摘要：

  对映体（R）-美西律汀是利用Jacobsen催化剂通过末端环氧化物的水解动力学拆分方法以简单实用的方式制备的。获得了高对映体纯度（98％ee），该方法非常适合工业规模放大。

  DOI：

  10.1016/j.tetasy.2009.11.014

文献信息

• Bacillus alcalophilus MTCC10234 catalyzed enantioselective kinetic resolution of aryl glycidyl ethers
  作者：Neeraj Bala、Swapandeep Singh Chimni、Harvinder Singh Saini、Bhupinder Singh Chadha

  DOI：10.1016/j.molcatb.2009.12.019

  日期：2010.5

  The phenyl glycidyl ether derivatives have been kinetically resolved with the growing cells of Bacillus alcalophilus MTCC10234 yielding (S)-epoxides with up to >99% ee and (R)-diols with up to 89% ee. The enantiomeric ratio (E) of up to 67 has been obtained for biohydrolysis process. The effect of different substituents of phenyl glycidyl ether on the biocatalytic efficiency of B. alcalophilus MTCC10234

  苯缩水甘油醚衍生物已经与嗜碱芽孢杆菌MTCC10234的生长细胞动力学分离，产生了（S）-环氧化合物，其ee含量高达> 99％，（R）-二醇的ee含量高达89％。对于生物水解过程，已获得高达67的对映体比率（E）。苯基缩水甘油基醚的不同取代基对嗜酸芽孢杆菌MTCC10234的生物催化效率的影响表明，甲基和氯取代的芳基缩水甘油基醚衍生物较为可取，而硝基衍生物的转化速度较慢。将含有在两个邻位均具有甲基的大体积芳基的2，6-二甲基苯基缩水甘油醚用N-甲基-N-二甲基苯甲酸酯进行拆分。E  = 39。
• Discovery, synthesis, and biological evaluation of piperidinol analogs with anti-tuberculosis activity
  作者：Dianqing Sun、Michael S. Scherman、Victoria Jones、Julian G. Hurdle、Lisa K. Woolhiser、Susan E. Knudson、Anne J. Lenaerts、Richard A. Slayden、Michael R. McNeil、Richard E. Lee

  DOI：10.1016/j.bmc.2009.04.005

  日期：2009.5

  Direct anti-tuberculosis screening of commercially available compound libraries identified a novel piperidinol with interesting anti-tuberculosis activity and drug like characteristics. To generate a structure activity relationship about this hit a 22 member optimization library was generated using parallel synthesis. Products of this library 1-((R)-3-(4-chlorophenoxy)-2-hydroxypropyl)-4-(4-chloro-3-(trifluoromethyl) phenyl) piperidin-4-ol and 1-((S)-3-(4-(trifluoromethyl) phenoxy)-2-hydroxypropyl)-4-(4-chloro-3-( trifluoromethyl) phenyl) piperidin-4-ol demonstrated good anti-tuberculosis activity. Unfortunately, side effects were observed upon in vivo anti-tuberculosis testing of these compounds precluding their further advancement, which may be in part due to the secondary pharmacology associated with the aryl piperidinol core. (C) 2009 Elsevier Ltd. All rights reserved.
• Chiral aziridine ring opening: facile synthesis of (R)-mexiletine and (R)-phenoxybenzamine hydrochloride
  作者：N. Viswanadh、R. Velayudham、S. Jambu、M. Sasikumar、M. Muthukrishnan

  DOI：10.1016/j.tetlet.2015.07.032

  日期：2015.9

  A simple and efficient synthesis of chiral drugs (R)-mexiletine 1, an anti-arrhythmic drug and (R)-phenoxybenzamine hydrochloride 2, an anti-hypertensive drug has been described via controlled reductive ring opening of chiral aziridine as a key step. The target compounds 1 and 2 were obtained in overall yields of 34% and 10.5%, respectively. (C) 2015 Elsevier Ltd. All rights reserved.
• A convenient synthesis of enantiomerically pure (R)-mexiletine using hydrolytic kinetic resolution method
  作者：Murugesan Sasikumar、Milind D. Nikalje、Murugan Muthukrishnan

  DOI：10.1016/j.tetasy.2009.11.014

  日期：2009.12

  Enantiopure (R)-mexiletine was prepared in a simple and practical way using hydrolytic kinetic resolution method of terminal epoxide by Jacobsen’s catalyst. High enantiomeric purity (98% ee) was achieved and the method is well amenable to industrial scale-up.

  对映体（R）-美西律汀是利用Jacobsen催化剂通过末端环氧化物的水解动力学拆分方法以简单实用的方式制备的。获得了高对映体纯度（98％ee），该方法非常适合工业规模放大。