trans-(1R,2S)-2-(3,4-difluoro-phenyl)-cyclopropanecarboxylic acid ethyl ester | 2051515-21-8

• 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: trans-(1R,2S)-2-(3,4-difluoro-phenyl)-cyclopropanecarboxylic acid ethyl ester
• 英文别名: (1R,2S)-2-(3,4-difluorophenyl)-cyclopropylcarboxylic acid ethyl ester；QZ4L85YS6N；ethyl (1R,2S)-2-(3,4-difluorophenyl)cyclopropane-1-carboxylate
• CAS: 2051515-21-8；1414348-37-0
• 化学式: C₁₂H₁₂F₂O₂
• 分子量: 226.223
• InChiKey: WKJJNMWERMSARF-RKDXNWHRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  3,4-二氟溴苯 、 2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)cyclopropanecarboxylic acid ethyl ester 在 di-(1-adamantyl)-n-butylphosphine 、 palladium diacetate 、 caesium carbonate 作用下， 以 甲苯 为溶剂， 以66%的产率得到trans-(1R,2S)-2-(3,4-difluoro-phenyl)-cyclopropanecarboxylic acid ethyl ester
  参考文献：
  名称：

  面向多样性的环丙烷构件的酶促合成

  摘要：

  尽管生物催化越来越多地纳入药物开发流程，但在药物发现的早期阶段却很少使用。通过工程化蛋白质以产生具有可衍生功能手柄的手性基序，生物催化剂可用于帮助产生用于药物发现的多种结构单元。在这里，我们展示了罗丹色海藻一氧化氮双加氧酶（Rma NOD）的两个变体工程化，以催化频哪醇硼酸酯取代的环丙烷的顺式和反式非对映异构体的形成，可以容易地将其衍生化以生成各种立体纯的环丙烷构件。

  DOI：

  10.1021/acscatal.0c01888

文献信息

• Chemoselective Cyclopropanation over Carbene Y–H Insertion Catalyzed by an Engineered Carbene Transferase
  作者：Eric J. Moore、Viktoria Steck、Priyanka Bajaj、Rudi Fasan

  DOI：10.1021/acs.joc.8b00946

  日期：2018.7.20

  biocatalysts for promoting a variety of carbene transfer reactions including cyclopropanation and Y–H insertion (Y = N, S, Si, B). For these and synthetic carbene transfer catalysts alike, achieving high chemoselectivity toward cyclopropanation in olefin substrates bearing unprotected Y–H groups has proven remarkably challenging due to competition from the more facile carbene Y–H insertion reaction. In this

  血红蛋白最近已成为有希望的生物催化剂，可用于促进各种卡宾转移反应，包括环丙烷化和Y–H插入（Y = N，S，Si，B）。对于这些和合成卡宾转移催化剂，由于与更简便的卡宾Y–H插入反应之间的竞争，事实证明，在带有未保护的Y–H基团的烯烃底物中，对环丙烷化具有很高的化学选择性。在本报告中，我们描述了一种基于工程化的肌红蛋白的新型人工金属酶的开发，该酶结合了丝氨酸连接的卟啉辅因子，能够通过NH和Si-H插入对烯烃环丙烷化提供高选择性。分子内竞争实验显示Mb（H64V，V68A，卡宾转移反应中的H93S）[Co（ppIX）]变体与含有天然组氨酸连接的血红素辅因子或其他金属/近端配体取代的基于肌红蛋白的变体相比。这些研究突出了肌红蛋白作为“卡宾转移酶”的功能可塑性，并说明了在该金属蛋白支架内调节辅因子环境如何代表获得天然血红蛋白或过渡金属催化剂未表现出的卡宾转移反应性的有价值的策略。
• Selective 5-Hydroxytryptamine 2C Receptor Agonists Derived from the Lead Compound Tranylcypromine: Identification of Drugs with Antidepressant-Like Action
  作者：Sung Jin Cho、Niels H. Jensen、Toru Kurome、Sudhakar Kadari、Michael L. Manzano、Jessica E. Malberg、Barbara Caldarone、Bryan L. Roth、Alan P. Kozikowski

  DOI：10.1021/jm801354e

  日期：2009.4.9

  We report here the design, synthesis, and pharmacological properties of a series of compounds related to tranylcypromine (9), which itself was discovered as a lead compound in a high-throughput screening campaign. Starting from 9, which shows modest activity as a 5-HT2C agonist, a series of 1-aminomethyl-2-phenylcyclopropanes was investigated as 5-HT2C agonists through iterative structural modifications. Key pharmacophore feature of this new class of ligands is a 2-aminomethyl-trans-cyclopropyl side chain attached to a substituted benzene ring. Among the tested compounds, several were potent and efficacious 5-HT2C receptor agonists with selectivity over both 5-HT2A and 5-HT2B receptors in functional assays. The most promising compound is 37, with 120- and 14-fold selectivity over 5-HT2A and 5-HT2B, respectively (EC50 = 585, 65, and 4.8 nM at the 2A, 2B, and 2C subtypes, respectively). In animal studies, compound 37 (10-60 mg/kg) decreased immobility time in the mouse forced swim test.
• [EN] HEMOPROTEIN CATALYSTS FOR IMPROVED ENANTIOSELECTIVE ENZYMATIC SYNTHESIS OF TICAGRELOR<br/>[FR] CATALYSEURS À BASE D'HÉMOPROTÉINES PERMETTANT D'AMÉLIORER LA SYNTHÈSE ÉNANTIOSÉLECTIVE ENZYMATIQUE DU TICAGRELOR
  申请人：CALIFORNIA INST OF TECHN

  公开号：WO2016191612A3

  公开（公告）日：2017-01-19
• HEMOPROTEIN CATALYSTS FOR IMPROVED ENANTIOSELECTIVE ENZYMATIC SYNTHESIS OF TICAGRELOR
  申请人：California Institute of Technology

  公开号：US20180148745A1

  公开（公告）日：2018-05-31

  The present invention provides methods by which trans-(1R,2S)-2-(3,4-difluorophenyl)-cyclopropylamine and related cyclopropane compounds are prepared using synthetic strategies that include a biocatalytic cyclopropanation step.