(6,6-dimethyl-bicyclo[3.1.1]hept-2-en-2-ylmethylene)aniline

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: (6,6-dimethyl-bicyclo[3.1.1]hept-2-en-2-ylmethylene)aniline
• 英文别名: N-(((1R,5S)-6,6-dimethylbicyclo[3.1.1]hept-2-en-2-yl)methyl)aniline；1-[(1R,5S)-6,6-dimethyl-2-bicyclo[3.1.1]hept-2-enyl]-N-phenylmethanimine
• 化学式: C₁₆H₁₉N
• 分子量: 225.334
• InChiKey: DGSSDYANFLGMLT-ZFWWWQNUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  12.4
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  (6,6-dimethyl-bicyclo[3.1.1]hept-2-en-2-ylmethylene)aniline 在 sodium tetrahydroborate 作用下， 以 甲醇 为溶剂， 生成 (1R,5R)-(-)-2-anilinomethyl-6,6-dimethylbicyclo<3.1.1>-2-heptene
  参考文献：
  名称：

  The Development of Tyrosyl-DNA Phosphodyesterase 1 (TDP1) Inhibitors Based on the Amines Combining Aromatic/Heteroaromatic and Monoterpenoid Moieties

  摘要：

  背景：抑制DNA修复酶酪基-DNA磷酸二酯酶1（TDP1）可能增加对导致肿瘤细胞DNA损伤的抗癌药物的疗效。在已知的TDP1抑制剂中，有含有天然物质部分的化合物，例如单萜类化合物。在这项工作中，我们合成了几种含有芳香/杂芳胺和单萜类基团的化合物，并评估了它们对TDP1的抑制潜力。 方法：所有合成化合物的结构均通过1H和13C核磁共振以及高分辨质谱确认。芳胺的TDP1抑制活性是通过实时荧光寡核苷酸生物传感器确定的。 结果：合成的二级胺的TDP1抑制活性IC50在0.79-9.2 µM范围内。发现（-）-没药醛衍生物中含有对溴苯胺或m-(三氟甲基)苯胺残基的最高活性。 结论：我们合成了22种二级胺；其中，17种是新颖的化学结构。许多胺在低微摄米范围内抑制TDP1活性。因此，这些化合物在与DNA损伤药物联合研究其抗增殖活性方面具有潜力。

  DOI：

  10.2174/1570180816666181220121042
• 作为产物：
  描述：

  桃金娘烯醛 、 苯胺 以 甲醇 为溶剂， 以94%的产率得到(6,6-dimethyl-bicyclo[3.1.1]hept-2-en-2-ylmethylene)aniline
  参考文献：
  名称：

  3D-printed devices for continuous-flow organic chemistry

  摘要：

  我们提出了一项研究，结合了3D打印的多功能性和流动化学的加工优势，用于有机化合物的合成。坚固且廉价的3D打印反应器设备可以轻松地使用标准配件连接，形成复杂的、定制的流动系统，包括多个串联的反应器，并使用ATR-IR流动池进行在线实时分析。作为概念验证，我们利用了两种有机反应，亚胺合成和亚胺还原，展示了不同的反应器配置和底物会产生不同的产物。

  DOI：

  10.3762/bjoc.9.109

文献信息

• One-pot monoterpene alcohol amination over Au/ZrO2 catalyst: Effect of the substrate structure
  作者：Yu. S. Demidova、E.V. Suslov、I.L. Simakova、E.S. Mozhajcev、D.V. Korchagina、K.P. Volcho、N.F. Salakhutdinov、A. Simakov、D. Yu. Murzin

  DOI：10.1016/j.jcat.2018.01.020

  日期：2018.4

  for myrtenol, increasing selectivity to the amine. The influence of secondary transformation was more noticeable for monocyclic perillyl alcohol with a conjugated –OH group. Myrtenol amination was explored with a range of aliphatic and aromatic amines, showing that the primary amine structure affected both the initial dehydrogenation rate and the selectivity to the desired amine. A good correlation was

  在Au / ZrO 2上研究了一锅法天然单萜醇的胺化催化剂，着重于根据药物相关性选择的底物的结构效果。在可比较的条件下，选择了双环（myrtenol和nopol，带有一个未结合的–OH基）和单环（紫苏）醇进行苯胺胺化。Nopol的使用使反应速率比肉豆蔻醇降低了十倍，从而提高了对胺的选择性。对于具有共轭-OH基团的单环紫苏醇，二次转化的影响更为明显。用一系列脂族和芳族胺探索了肉豆蔻胺的胺化反应，表明伯胺结构既影响初始脱氢速率，又影响对所需胺的选择性。使用Hammett方程发现底物结构与反应性之间具有良好的相关性。醇脱氢所需的δ+可用性。作为氢供体引入的丙醇2提高了目标胺的收率。
• 3D-printed devices for continuous-flow organic chemistry
  作者：Vincenza Dragone、Victor Sans、Mali H Rosnes、Philip J Kitson、Leroy Cronin

  DOI：10.3762/bjoc.9.109

  日期：——

  We present a study in which the versatility of 3D-printing is combined with the processing advantages of flow chemistry for the synthesis of organic compounds. Robust and inexpensive 3D-printed reactionware devices are easily connected using standard fittings resulting in complex, custom-made flow systems, including multiple reactors in a series with in-line, real-time analysis using an ATR-IR flow cell. As a proof of concept, we utilized two types of organic reactions, imine syntheses and imine reductions, to show how different reactor configurations and substrates give different products.

  我们提出了一项研究，结合了3D打印的多功能性和流动化学的加工优势，用于有机化合物的合成。坚固且廉价的3D打印反应器设备可以轻松地使用标准配件连接，形成复杂的、定制的流动系统，包括多个串联的反应器，并使用ATR-IR流动池进行在线实时分析。作为概念验证，我们利用了两种有机反应，亚胺合成和亚胺还原，展示了不同的反应器配置和底物会产生不同的产物。
• Selectivity control in one-pot myrtenol amination over Au/ZrO2 by molecular hydrogen addition
  作者：Yu. S. Demidova、E.V. Suslov、I.L. Simakova、E.S. Mozhajcev、D.V. Korchagina、K.P. Volcho、N.F. Salakhutdinov、A. Simakov、D. Yu. Murzin

  DOI：10.1016/j.molcata.2016.10.034

  日期：2017.1

  The one-pot myrtenol amination was studied over Au (3 wt.%)/ZrO2 catalyst under mixed N-2/H-2 atmosphere (9 bar). The effect of hydrogen addition was explored with the aim to increase selectivity to the target amines. Hydrogen addition timing depending on myrtenol conversion and hydrogenation temperature affected selectivity to the reaction products. Hydrogen addition (1 bar) after almost complete myrtenol conversion at 100 degrees C increased the yield to amine up to 68% preserving C=C bond in the initial myrtenol structure. Hydrogen addition at 180 degrees C irrespective of the myrtenol conversion level provoked reduction of both C=C and C=N bonds with formation of two diastereomers (yield up to 93%), with trans isomer formation being preferred when hydrogen was added at almost complete myrtenol conversion. It was shown, that in the presence of a gold catalyst controlled hydrogenation of competitive C=C and C=N groups can be performed during one-pot alcohol amination by regulation of the reaction conditions. (C) 2016 Elsevier B.V. All rights reserved.
• The Development of Tyrosyl-DNA Phosphodyesterase 1 (TDP1) Inhibitors Based on the Amines Combining Aromatic/Heteroaromatic and Monoterpenoid Moieties
  作者：Evgenii Mozhaitsev、Evgenii Suslov、Yuliya Demidova、Dina Korchagina、Konstantin Volcho、Alexandra Zakharenko、Inna Vasil'eva、Maksim Kupryushkin、Arina Chepanova、Daniel Moscoh Ayine-Tora、Jóhannes Reynisson、Nariman Salakhutdinov、Olga Lavrik

  DOI：10.2174/1570180816666181220121042

  日期：2019.4.15

  Inhibition of the DNA repair enzyme, tyrosyl-DNA phosphodiesterase 1 (TDP1), may increase the efficacy of cancer drugs that cause damage to tumor cell DNA. Among the known TDP1 inhibitors, there are compounds containing moieties of natural substances, e.g., monoterpenoids. In this work, we synthesized several compounds containing aromatic/ heteroaromatic amines and monoterpenoid groups and assessed their TDP1 inhibition potential.

  Structures of all the synthesized compounds were confirmed by 1H and 13C NMR as well as HRMS. The TDP1 inhibitory activity of the amines was determined by real-time fluorescence oligonucleotide biosensor.

  The synthesized secondary amines had TDP1 inhibitory activity IC50 in the range of 0.79-9.2 µM. The highest activity was found for (–)-myrtenal derivatives containing p-bromoaniline or m-(trifluoromethyl)aniline residue.

  We synthesized 22 secondary amines; of these, 17 amines are novel chemical structures. Many of the amines inhibit TDP1 activity in the low micromolar range. Therefore, these compounds are promising for further study of their antiproliferative activity in conjunction with DNA damaging drugs.

  背景：抑制DNA修复酶酪基-DNA磷酸二酯酶1（TDP1）可能增加对导致肿瘤细胞DNA损伤的抗癌药物的疗效。在已知的TDP1抑制剂中，有含有天然物质部分的化合物，例如单萜类化合物。在这项工作中，我们合成了几种含有芳香/杂芳胺和单萜类基团的化合物，并评估了它们对TDP1的抑制潜力。 方法：所有合成化合物的结构均通过1H和13C核磁共振以及高分辨质谱确认。芳胺的TDP1抑制活性是通过实时荧光寡核苷酸生物传感器确定的。 结果：合成的二级胺的TDP1抑制活性IC50在0.79-9.2 µM范围内。发现（-）-没药醛衍生物中含有对溴苯胺或m-(三氟甲基)苯胺残基的最高活性。 结论：我们合成了22种二级胺；其中，17种是新颖的化学结构。许多胺在低微摄米范围内抑制TDP1活性。因此，这些化合物在与DNA损伤药物联合研究其抗增殖活性方面具有潜力。