4-{4-[(2S)-oxiran-2-ylmethoxy]-1,2,5-thiadiazol-3-yl}morpholine | 69500-53-4

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 4-{4-[(2S)-oxiran-2-ylmethoxy]-1,2,5-thiadiazol-3-yl}morpholine
• 英文别名: (R)-3-(2,3-epoxypropoxy)-4-(N-morpholino)-1,2,5-thiadiazole；(S)-4-[4-(oxiranylmethoxy)-1,2,5-thiadiazol-3-yl]morpholine；(S)-3-(2,3-epoxypropoxy)-4-morpholino-1,2,5-thiadiazole；4-(4-(S)-oxiranylmethoxy-[1,2,5]thiadiazol-3-yl)-morpholine；(S)-3-(2,3-Epoxy-1-propoxy)-4-morpholino-1,2,5-thiadiazol；4-[4-[[(2S)-oxiran-2-yl]methoxy]-1,2,5-thiadiazol-3-yl]morpholine
• CAS: 69500-53-4
• 化学式: C₉H₁₃N₃O₃S
• 分子量: 243.287
• InChiKey: ZGZYFNICRHUUGD-ZETCQYMHSA-N

物化性质

• 熔点：
  111-114°C
• 溶解度：
  可溶于氯仿（少许）、甲醇（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.78
• 拓扑面积：
  88.2
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  4-{4-[(2S)-oxiran-2-ylmethoxy]-1,2,5-thiadiazol-3-yl}morpholine 在 potassium iodide 作用下， 以 四氢呋喃 为溶剂， 反应 73.0h， 生成 (S)-马来酸噻吗洛尔
  参考文献：
  名称：

  Enantioselective synthesis of (S)-timolol via kinetic resolution of terminal epoxides and dihydroxylation of allylamines

  摘要：

  An efficient enantioselective synthesis of (S)-timolol has been described using chiral Co-salen-catalyzed kinetic resolution of less expensive (+/-)-epichlorohydrin with 3-hydroxy-4-(N-morpholino)-1,2,5-thiadiazole in good overall yield (55%) and excellent enantioselectivity (98%). Synthesis of (S)-timolol has also been achieved using hydrolytic kinetic resolution as well as asymmetric dihydroxylation routes in 90% ee and 56% ee, respectively. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2007.01.057
• 作为产物：
  描述：

  4-吗啉-4-基-1,2,5-三唑-3-酮 在 (S,S)-salen-cobalt(II) potassium tert-butylate 、 溶剂黄146 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 13.0h， 生成 4-{4-[(2S)-oxiran-2-ylmethoxy]-1,2,5-thiadiazol-3-yl}morpholine
  参考文献：
  名称：

  Enantioselective synthesis of (S)-timolol via kinetic resolution of terminal epoxides and dihydroxylation of allylamines

  摘要：

  An efficient enantioselective synthesis of (S)-timolol has been described using chiral Co-salen-catalyzed kinetic resolution of less expensive (+/-)-epichlorohydrin with 3-hydroxy-4-(N-morpholino)-1,2,5-thiadiazole in good overall yield (55%) and excellent enantioselectivity (98%). Synthesis of (S)-timolol has also been achieved using hydrolytic kinetic resolution as well as asymmetric dihydroxylation routes in 90% ee and 56% ee, respectively. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2007.01.057

文献信息

• [EN] SYNTHESIS OF DENTIMOL, AN ANTIGLAUCOMA DRUG<br/>[FR] SYNTHÈSE DE DENTIMOL, MÉDICAMENT ANTI-GLAUCOME
  申请人：UNIV VIRGINIA COMMONWEALTH

  公开号：WO2019202519A1

  公开（公告）日：2019-10-24

  Compounds, comprising a selective β-blocker coupled to a PAMAM dendrimer via a flexible spacer, and compositions containing the compounds, are provided. Methods of making and using the compounds and compositions for the treatment of glaucoma and other maladies are also provided.

  提供了包含选择性β受体阻滞剂通过柔性间隔子与PAMAM树枝状聚合物偶联的化合物，以及含有这些化合物的组合物。还提供了制备和使用这些化合物和组合物用于治疗青光眼和其他疾病的方法。
• 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。
• Biocatalytic Asymmetric Synthesis of (<i>S</i>)- and (<i>R</i>)-Timolol
  作者：Fabio Prati、Giovanni Tosi、Federica Zironi、Emilia Caselli、Arrigo Forni

  DOI：10.1055/s-2004-822395

  日期：——

  A new biocatalytic route for the synthesis of both enantiomers of Timolol (1) is described. Starting from 3,4-dichloro1,2,5-thiadiazole (2), (R)- and (S)-Timolol (87% ee) were obtained in 35% and 30% overall yield, respectively. Asymmetric reduction of the intermediate haloketone 5 with baker's yeast afforded the corresponding halohydrin 6 in the optically active form (87% ee), which gave the R enantiomer

  描述了合成噻吗洛尔 (1) 的两种对映异构体的新生物催化途径。从 3,4-二氯 1,2,5-噻二唑 (2) 开始，(R)- 和 (S)-噻吗洛尔 (87% ee) 分别以 35% 和 30% 的总产率获得。用面包酵母不对称还原中间体卤代酮5，得到光学活性形式的相应卤代醇6（87% ee），得到噻吗洛尔的R对映异构体（二异构体）。S 对映异构体 (eutomer) 是通过在 Mitsunobu 程序后反转卤代醇的构型获得的。
• Arenesulfonate derivatives of homochiral glycidol: versatile chiral building blocks for organic synthesis
  作者：Janice M. Klunder、Tetsuo Onami、K. Barry Sharpless

  DOI：10.1021/jo00267a014

  日期：1989.3
• Chiral heteroaryloxymethyloxiranes
  作者：David E. McClure、Edward L. Engelhardt、Kathleen Mensler、Stella King、Walfred S. Saari、Joel R. Huff、John J. Baldwin

  DOI：10.1021/jo01325a017

  日期：1979.5