(R)-1,2-epoxy-3-(2,3-dimethylphenoxy)propane | 1616790-45-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: (R)-1,2-epoxy-3-(2,3-dimethylphenoxy)propane
• 英文别名: (2R)-2-[(2,3-dimethylphenoxy)methyl]oxirane
• CAS: 1616790-45-4
• 化学式: C₁₁H₁₄O₂
• 分子量: 178.231
• InChiKey: RWBSWKZPQXYNNO-SNVBAGLBSA-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：

  (R)-1,2-epoxy-3-(2,3-dimethylphenoxy)propane 在 盐酸 作用下， 以 乙醚 、 水 为溶剂， 反应 0.25h， 生成 (R)-xibenolol hydrochloride
  参考文献：
  名称：

  Synthesis, crystal structure, and absolute configuration of the enantiomers of chiral drug xibenolol hydrochloride

  摘要：

  Based on the features of its crystallization, racemic 3-(2,3-dimethylphenoxy)propane-1,2-diol 2, the synthetic precursor of the chiral drug xibenolol 1, was resolved into pure enantiomers by the direct method of entrainment. The enantiomers of diol 2 through a Mitsunobu reaction were converted into the nonracemic 1,2-epoxy-3-(2,3-dimethylphenoxy)propanes (S)- and (R)-3, and then into the xibenolol enantiomers. Single crystals of (+)- and (-)-1 center dot HCl were studied by X-ray diffraction. On the basis of the Flack parameter, the absolute (R)- and (S)-configurations were assigned to these compounds and to the other intermediate chiral substances. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetasy.2017.08.013
• 作为产物：
  描述：

  (R)-3-(2,3-dimethylphenoxy)propane-1,2-diol 在 偶氮二甲酸二异丙酯 、 三苯基膦 作用下， 以 四氢呋喃 为溶剂， 反应 24.0h， 以45%的产率得到(R)-1,2-epoxy-3-(2,3-dimethylphenoxy)propane
  参考文献：
  名称：

  Synthesis, crystal structure, and absolute configuration of the enantiomers of chiral drug xibenolol hydrochloride

  摘要：

  Based on the features of its crystallization, racemic 3-(2,3-dimethylphenoxy)propane-1,2-diol 2, the synthetic precursor of the chiral drug xibenolol 1, was resolved into pure enantiomers by the direct method of entrainment. The enantiomers of diol 2 through a Mitsunobu reaction were converted into the nonracemic 1,2-epoxy-3-(2,3-dimethylphenoxy)propanes (S)- and (R)-3, and then into the xibenolol enantiomers. Single crystals of (+)- and (-)-1 center dot HCl were studied by X-ray diffraction. On the basis of the Flack parameter, the absolute (R)- and (S)-configurations were assigned to these compounds and to the other intermediate chiral substances. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetasy.2017.08.013

文献信息

• A Smart Library of Epoxide Hydrolase Variants and the Top Hits for Synthesis of (<i>S</i>)-β-Blocker Precursors
  作者：Xu-Dong Kong、Qian Ma、Jiahai Zhou、Bu-Bing Zeng、Jian-He Xu

  DOI：10.1002/anie.201402653

  日期：2014.6.23

  the enzyme active pocket has led to a smart library of epoxide hydrolase variants with an expanded substrate spectrum covering a series of typical β‐blocker precursors. Improved activities of 6‐ to 430‐fold were achieved by redesigning the active site at two predicted hot spots. This study represents a breakthrough in protein engineering of epoxide hydrolases and resulted in enhanced activity toward

  酶活性口袋的微调已形成了环氧水解酶变体的智能库，其底物光谱范围扩大，涵盖了一系列典型的β-受体阻滞剂前体。通过在两个预计的热点上重新设计活动站点，可以将活动提高6到430倍。这项研究代表了环氧化物水解酶蛋白质工程的一项突破，并提高了对庞大底物的活性。
• Enantiocomplementary synthesis of β-adrenergic blocker precursors via biocatalytic nitration of phenyl glycidyl ethers
  作者：Hui-Hui Wang、Nan-Wei Wan、Xin-Yu Da、Xue-Qing Mou、Zhu-Xiang Wang、Yong-Zheng Chen、Zhi-Qiang Liu、Yu-Guo Zheng

  DOI：10.1016/j.bioorg.2023.106640

  日期：2023.9

  important class of nitro-containing compounds, are essential building blocks in pharmaceutical and organic chemistry, particularly for the synthesis of β-adrenergic blockers. In this study, we present the successful protein engineering of halohydrin dehalogenase HHDHamb for the enantioselective bio-nitration of various phenyl glycidyl ethers to the corresponding chiral β-nitroalcohols, using the inexpensive

  对映体纯β-硝基醇作为一类重要的含硝基化合物，是药物和有机化学中必不可少的基础材料，特别是对于β-肾上腺素能阻滞剂的合成。在这项研究中，我们展示了卤代醇脱卤酶 HHDHamb 的成功蛋白质工程，使用廉价、市售且更安全的亚硝酸盐作为硝化剂，将各种苯基缩水甘油醚对映选择性生物硝化为相应的手性 β-硝基醇。几种对映互补的HHDHamb变体通过全细胞生物转化合成了手性( R )-和( S )-1-硝基-3-苯氧基丙-2-醇，表现出良好的催化效率（分离产率高达43%）和高光学纯度（高达>99% ee ）。此外，我们还证明生物硝化方法能够耐受 1000 mM (150 g/L) 高浓度的底物。此外，利用相应的手性β-硝基醇作为前体，成功合成了β-肾上腺素能阻滞剂美托洛尔的两种光学活性对映体。
• 5-HT1F antagonists
  申请人：ELI LILLY AND COMPANY

  公开号：EP0976746A1

  公开（公告）日：2000-02-02

  This invention provides 5-HT1f antagonists of Formula I: where AR1, AR2, R, and R' are as defined in the specification.

  本发明提供了式 I 的 5-HT1f 拮抗剂： 其中 AR1、AR2、R 和 R' 如说明书中所定义。
• Use of 5HT-1F receptor antagonists for treating anxiety disorders
  申请人：ELI LILLY AND COMPANY

  公开号：EP0976747A2

  公开（公告）日：2000-02-02

  The present invention provides a method for the treatment of prevention of anxiety disorders which comprises administering to a mammal in need of such treatment a serotonin 5-HT1F receptor antagonist.

  本发明提供了一种治疗和预防焦虑症的方法，该方法包括向需要治疗的哺乳动物施用5-羟色胺5-HT1F受体拮抗剂。
• US6242450B1
  申请人：——

  公开号：US6242450B1

  公开（公告）日：2001-06-05