(3Z)-3-[(4-nitrophenyl)methylene]-4H-tetrahydrothiapyran-4-one

• 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: (3Z)-3-[(4-nitrophenyl)methylene]-4H-tetrahydrothiapyran-4-one
• 英文别名: (Z)-3-(4-nitrobenzylidene)dihydro-2H-thiopyran-4(3H)-one；(3Z)-3-[(4-nitrophenyl)methylidene]thian-4-one
• 化学式: C₁₂H₁₁NO₃S
• 分子量: 249.29
• InChiKey: ASYPTKOUHDVDFI-JXMROGBWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  88.2
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (3Z)-3-[(4-nitrophenyl)methylene]-4H-tetrahydrothiapyran-4-one 在 盐酸 、 间氯过氧苯甲酸 作用下， 以 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 16.0h， 生成 (3Z,5Z)-3-[(4-hydroxyphenyl)methylene]-5-[(4-nitrophenyl)methylene]-4H-tetrahydrothiapyran-4-one 1,1-dioxide
  参考文献：
  名称：

  Synthesis, Characterization, and Optimization for in Vivo Delivery of a Nonselective Isopeptidase Inhibitor as New Antineoplastic Agent

  摘要：

  Bis-arylidenecycloalkanones structurally related to the nonselective isopeptidase inhibitor G5 were synthesized and tested for cytotoxic activity against glioblastoma cells. Cytotoxicities correlate well with Hammett s constants for substituted arylidene groups, confirming the proposed inhibition mechanism. A new inhibitor (2c) based on the 4-hydroxycyclohexanone scaffold, which favors apoptosis over necrosis, was selected for further development. 2c inhibited representative deubiquitinases with micromolar IC50, and its proapoptotic activity was studied on several cancer cell lines. Inhibitor 2c was conjugated to PEG via dicarbamate and diester linkers. While the dicarbamate was inactive, the diester (2cPE) behaves like a prodrug and is converted into the active species 2c by secreted esterase activities. Finally, 2cPE was also tested in vivo on A549 lung carcinoma xenografts generated in mice. Intravenous treatment with 2cPE led to a significant reduction in primary tumor growth, without appreciable toxicity to mice.

  DOI：

  10.1021/jm501336h
• 作为产物：
  描述：

  四氢噻喃-4-酮 、 对硝基苯甲醛 在 N,N-二甲基三甲基硅胺 、 iron oxide 作用下， 以 neat (no solvent) 为溶剂， 反应 4.0h， 以72%的产率得到(3Z)-3-[(4-nitrophenyl)methylene]-4H-tetrahydrothiapyran-4-one
  参考文献：
  名称：

  Fe3O4 纳米粒子作为一种高效且磁性可恢复的催化剂，用于在无溶剂条件下合成 α,β-不饱和杂环和环状酮

  摘要：

  摘要 开发了一种高效、绿色的合成环和杂环酮单芳基的方法。该反应在无溶剂条件下在催化量的纳米磁铁矿 (Fe3O4) 存在下进行。使用外部磁铁可以轻松去除催化剂。产物的结构由它们的 1H NMR、13C NMR、红外光谱和质谱推断。[本文提供补充材料。访问出版商的 Synthetic Communications® 在线版，获取以下免费补充资源：完整的实验和光谱细节。] 图形摘要

  DOI：

  10.1080/00397911.2013.786089

文献信息

• Proline-Catalyzed Ketone-Aldehyde Aldol Reactions are Accelerated by Water
  作者：Petri Pihko、Annika Nyberg、Annina Usano

  DOI：10.1055/s-2004-831296

  日期：——

  Proline-catalyzed aldol reactions between acetone or 4-thianone and different aldehydes are accelerated by addition of 1-10 equivalents of water to the reaction medium, allowing stoichiometric aldol reactions to proceed at acceptable rates.

  脯氨酸催化的丙酮或四氢噻吩-4-酮与不同醛之间的羟醛反应，通过向反应体系中添加1-10当量的水，可以加速反应进程，使得定量羟醛反应能够在可接受的速率下进行。
• An Efficient Procedure for the Synthesis of α,β-Unsaturated Ketones and Its Application to Heterocyclic Systems
  作者：Mohammad Mojtahedi、M. Abaee、Mehdi Khakbaz、Tooba Alishiri、Maedeh Samianifard、A. Mesbah、Klaus Harms

  DOI：10.1055/s-0031-1289571

  日期：2011.12

  An efficient and room-temperature procedure is developed for high yield synthesis of novel α,β-unsaturated derivatives of thiopyran 3 directly from ketone 1 and various aldehydes in the presence of catalytic quantities of TMSNMe2 and MgBr2˙OEt2 under solvent-free conditions. The main advantage of the procedure is that the formation of the undesired bis by-products is minimized. In addition, the procedure

  一种有效的和室温过程，噻喃的β不饱和衍生物为新颖α的高收率合成开发3从酮直接1和各种醛在TMSNMe的催化量存在2和MgBr 2 OET 2下的无溶剂条件。该方法的主要优点是使不希望的双副产物的形成最小。另外，该方法适用于其他可烯化的碳环和非环酮。 α，β-不饱和酮-噻喃-4-酮-溴化镁醚化物-醛醇缩合
• Fe₃O₄ Nanoparticles as an Efficient and Magnetically Recoverable Catalyst for the Synthesis of <font>α</font>,<font>β</font>-Unsaturated Heterocyclic and Cyclic Ketones under Solvent-Free Conditions
  作者：Tooba Alishiri、Hossein A. Oskooei、Majid M. Heravi

  DOI：10.1080/00397911.2013.786089

  日期：2013.12.17

  Abstract An efficient and green procedure has been developed for the synthesis of monoarylidenes of cyclic and heterocyclic ketones. The reaction was carried out under solvent-free conditions in the presence of a catalytic amount of nanosized magnetite (Fe3O4). The catalyst was easily removed by using an external magnet. The structures of the products were deduced from their 1H NMR, 13C NMR, and infrared

  摘要 开发了一种高效、绿色的合成环和杂环酮单芳基的方法。该反应在无溶剂条件下在催化量的纳米磁铁矿 (Fe3O4) 存在下进行。使用外部磁铁可以轻松去除催化剂。产物的结构由它们的 1H NMR、13C NMR、红外光谱和质谱推断。[本文提供补充材料。访问出版商的 Synthetic Communications® 在线版，获取以下免费补充资源：完整的实验和光谱细节。] 图形摘要
• Synthesis, Characterization, and Optimization for in Vivo Delivery of a Nonselective Isopeptidase Inhibitor as New Antineoplastic Agent
  作者：Ulma Cersosimo、Andrea Sgorbissa、Carmen Foti、Sara Drioli、Rosario Angelica、Andrea Tomasella、Raffaella Picco、Marta Stefania Semrau、Paola Storici、Fabio Benedetti、Federico Berti、Claudio Brancolini

  DOI：10.1021/jm501336h

  日期：2015.2.26

  Bis-arylidenecycloalkanones structurally related to the nonselective isopeptidase inhibitor G5 were synthesized and tested for cytotoxic activity against glioblastoma cells. Cytotoxicities correlate well with Hammett s constants for substituted arylidene groups, confirming the proposed inhibition mechanism. A new inhibitor (2c) based on the 4-hydroxycyclohexanone scaffold, which favors apoptosis over necrosis, was selected for further development. 2c inhibited representative deubiquitinases with micromolar IC50, and its proapoptotic activity was studied on several cancer cell lines. Inhibitor 2c was conjugated to PEG via dicarbamate and diester linkers. While the dicarbamate was inactive, the diester (2cPE) behaves like a prodrug and is converted into the active species 2c by secreted esterase activities. Finally, 2cPE was also tested in vivo on A549 lung carcinoma xenografts generated in mice. Intravenous treatment with 2cPE led to a significant reduction in primary tumor growth, without appreciable toxicity to mice.