nopyl bromide | 132488-47-2

• 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: nopyl bromide
• 英文别名: (1R,5S)-2-(2-bromoethyl)-6,6-dimethylbicyclo[3.1.1]hept-2-ene
• CAS: 132488-47-2
• 化学式: C₁₁H₁₇Br
• 分子量: 229.16
• InChiKey: KHSVWSRFLOVLCW-UWVGGRQHSA-N

物化性质

• 沸点：
  238.6±19.0 °C(Predicted)
• 密度：
  1.234±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  12
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  0
• 氢给体数：
  0
• 氢受体数：
  0

反应信息

• 作为反应物：
  描述：

  nopyl bromide 在 2,2'-联吡啶 、 magnesium 、 lithium chloride 、 cobalt(II) chloride 作用下， 以 四氢呋喃 为溶剂， 反应 16.25h， 生成
  参考文献：
  名称：

  功能化烷基锌试剂与（杂）芳基卤化物的钴催化交叉偶联。

  摘要：

  10％CoCl2和20％2,2'-联吡啶配体的组合可实现官能化的伯烷基锌试剂和仲烷基锌试剂与各种（杂）芳基卤化物的交叉偶联。与1，3-和1，4-取代的环烷基锌试剂的偶联进行非对映选择性，导致官能化的杂环具有高达98：2的高非对映选择性。此外，炔基溴化物与伯和仲烷基锌试剂反应，提供烷基化的炔烃。

  DOI：

  10.1002/anie.201914490
• 作为产物：
  描述：

  (1R)-nopol tosylate 在 sodium bromide 作用下， 以 二甲基亚砜 为溶剂， 反应 2.0h， 以78%的产率得到nopyl bromide
  参考文献：
  名称：

  Synthesis of cardamom peroxide analogues by radical cyclization of hydroperoxyalkenes

  摘要：

  Three pinenic hydroperoxides were synthesized according to the Dussault method. Two of them could cyclize under radical conditions to give the exo-trig isomer as a single regioisomer. Only five- and six-member ring peroxides were obtained, whereas none of the possible seven-member ones was observed. This strategy could be employed in the total synthesis of cardamom peroxide. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4039(02)01122-x

文献信息

• Live-Cell Protein Modification by Boronate-Assisted Hydroxamic Acid Catalysis
  作者：Christopher Adamson、Hidetoshi Kajino、Shigehiro A. Kawashima、Kenzo Yamatsugu、Motomu Kanai

  DOI：10.1021/jacs.1c07060

  日期：2021.9.22

  Selective methods for introducing protein post-translational modifications (PTMs) within living cells have proven valuable for interrogating their biological function. In contrast to enzymatic methods, abiotic catalysis should offer access to diverse and new-to-nature PTMs. Herein, we report the boronate-assisted hydroxamic acid (BAHA) catalyst system, which comprises a protein ligand, a hydroxamic

  在活细胞中引入蛋白质翻译后修饰 (PTM) 的选择性方法已被证明对研究其生物学功能很有价值。与酶法相比，非生物催化应该提供对各种新自然 PTM 的访问。在此，我们报道了硼酸盐辅助的异羟肟酸（BAHA）催化剂体系，该体系由蛋白质配体、异羟肟酸路易斯碱和二醇部分组成。与带有硼酸的酰基供体配合，我们的催化剂利用局部摩尔浓度效应来促进酰基转移到目标赖氨酸残基。我们的催化剂系统采用微摩尔浓度的试剂，并提供最小的脱靶蛋白反应性。至关重要的是，BAHA 对谷胱甘肽具有抗性，谷胱甘肽是一种阻碍活细胞内非生物化学的许多努力的代谢物。在人体细胞中表达的大肠杆菌二氢叶酸还原酶。我们的结果进一步确立了众所周知的硼酸-二醇络合作为真正的生物正交反应，在化学生物学和细胞内催化中的应用。
• New Hybrid Compounds Combining Fragments of Usnic Acid and Monoterpenoids for Effective Tyrosyl-DNA Phosphodiesterase 1 Inhibition
  作者：Nadezhda S. Dyrkheeva、Aleksandr S. Filimonov、Olga A. Luzina、Alexandra L. Zakharenko、Ekaterina S. Ilina、Anastasia A. Malakhova、Sergey P. Medvedev、Jóhannes Reynisson、Konstantin P. Volcho、Suren M. Zakian、Nariman F. Salakhutdinov、Olga I. Lavrik

  DOI：10.3390/biom11070973

  日期：——

  phosphodiesterase 1 (TDP1). It can remove covalent complex DNA-topoisomerase 1 (TOP1) stabilized by the TOP1 inhibitor topotecan, neutralizing the effect of the drugs. TDP1 removes damage at the 3′ end of DNA caused by other anticancer agents. Thus, TDP1 is a promising therapeutic target for the development of drug combinations with topotecan, as well as other drugs for cancer treatment. Ten new UA enamino

  松萝酸 (UA) 是地衣的次生代谢产物，具有广泛的生物活性。以前，我们发现 UA 衍生物是酪氨酰 DNA 磷酸二酯酶 1 (TDP1) 的有效抑制剂。它可以去除由 TOP1 抑制剂拓扑替康稳定的共价复合体 DNA-拓扑异构酶 1 (TOP1)，中和药物的作用。TDP1 去除由其他抗癌药物引起的 DNA 3' 端的损伤。因此，TDP1 是开发与拓扑替康以及其他癌症治疗药物组合的有前景的治疗靶点。合成了 10 种新的 UA 烯氨基衍生物，它们的萜烯片段和 UA 骨架的取代基发生了变化，并作为 TDP1 抑制剂进行了测试。四种化合物11a - d 的IC 500.23–0.40 μM 范围内的值。分子模型显示11a - d具有相对较短的脂肪链，适合重要的结合域。11a - d的内在细胞毒性在两种人类细胞系上进行了测试。这些化合物对两种细胞系都具有低细胞毒性，CC 50 ≥ 60 μM。11a和1
• Hexabromoacetone and ethyl tribromoacetate: a highly efficient reagent for bromination of alcohol
  作者：Pratoomrat Tongkate、Wanchai Pluempanupat、Warinthorn Chavasiri

  DOI：10.1016/j.tetlet.2007.12.061

  日期：2008.2

  A new and efficient method for the bromination of alcohols utilizing Br3CCOCBr3/PPh3 and Br3CCO2Et/PPh3 is described. Various alcohols can be converted smoothly into their corresponding alkyl bromides in high yields under mild conditions with short reaction times. Based upon 1H NMR studies using competitive reactions between selected brominating agents and Cl3CCN, Br3CCOCBr3 displays the highest reactivity

  描述了一种利用Br 3 CCOCBr 3 / PPh 3和Br 3 CCO 2 Et / PPh 3进行醇溴化的新方法。各种醇可以在温和的条件下以短的反应时间，以高收率平稳地转化为它们相应的烷基溴。基于使用选定的溴化剂和Cl 3 CCN之间的竞争反应进行的1 H NMR研究，Br 3 CCOCBr 3的最高反应活性约为CBr 4的九倍。
• Promising New Inhibitors of Tyrosyl-DNA Phosphodiesterase I (Tdp 1) Combining 4-Arylcoumarin and Monoterpenoid Moieties as Components of Complex Antitumor Therapy
  作者：Tatyana M. Khomenko、Alexandra L. Zakharenko、Arina A. Chepanova、Ekaterina S. Ilina、Olga D. Zakharova、Vasily I. Kaledin、Valeriy P. Nikolin、Nelly A. Popova、Dina V. Korchagina、Jóhannes Reynisson、Raina Chand、Daniel M. Ayine-Tora、Jinal Patel、Ivanhoe K. H. Leung、Konstantin P. Volcho、Nariman F. Salakhutdinov、Olga I. Lavrik

  DOI：10.3390/ijms21010126

  日期：——

  Tyrosyl-DNA phosphodiesterase 1 (Tdp1) is an important DNA repair enzyme in humans, and a current and promising inhibition target for the development of new chemosensitizing agents due to its ability to remove DNA damage caused by topoisomerase 1 (Top1) poisons such as topotecan and irinotecan. Herein, we report our work on the synthesis and characterization of new Tdp1 inhibitors that combine the arylcoumarin (neoflavonoid) and monoterpenoid moieties. Our results showed that they are potent Tdp1 inhibitors with IC50 values in the submicromolar range. In vivo experiments with mice revealed that compound 3ba (IC50 0.62 µM) induced a significant increase in the antitumor effect of topotecan on the Krebs-2 ascites tumor model. Our results further strengthen the argument that Tdp1 is a druggable target with the potential to be developed into a clinically-potent adjunct therapy in conjunction with Top1 poisons.

  酪氨酸-DNA磷酸二酯酶1（Tdp1）是人类中重要的DNA修复酶，是开发新的化疗增敏剂的当前和有希望的抑制靶点，因为它能够去除由拓扑异构酶1（Top1）毒素（如托泊替康和伊立曲汀）引起的DNA损伤。在这里，我们报告了我们对合成和表征结合芳基香豆素（新黄酮类）和单萜类基团的新Tdp1抑制剂的工作。我们的结果显示，它们是有效的Tdp1抑制剂，其IC50值在亚微摮摩尔范围内。对小鼠进行的体内实验显示，化合物3ba（IC50值为0.62 µM）显著增加了托泊替康对Krebs-2腹水瘤模型的抗肿瘤效果。我们的结果进一步加强了Tdp1是一个可药用的靶点，并有潜力作为与Top1毒素联合使用的临床有效的辅助治疗方法的论点。
• Novel Tdp1 Inhibitors Based on Adamantane Connected with Monoterpene Moieties via Heterocyclic Fragments
  作者：Aldar A. Munkuev、Evgenii S. Mozhaitsev、Arina A. Chepanova、Evgeniy V. Suslov、Dina V. Korchagina、Olga D. Zakharova、Ekaterina S. Ilina、Nadezhda S. Dyrkheeva、Alexandra L. Zakharenko、Jóhannes Reynisson、Konstantin P. Volcho、Nariman F. Salakhutdinov、Olga I. Lavrik

  DOI：10.3390/molecules26113128

  日期：——

  Tyrosyl-DNA phosphodiesterase 1 (Tdp1) is a promising target for anticancer therapy due to its ability to counter the effects topoisomerase 1 (Top1) poison, such as topotecan, thus, decreasing their efficacy. Compounds containing adamantane and monoterpenoid residues connected via 1,2,4-triazole or 1,3,4-thiadiazole linkers were synthesized and tested against Tdp1. All the derivatives exhibited inhibition at low micromolar or nanomolar concentrations with the most potent inhibitors having IC50 values in the 0.35–0.57 µM range. The cytotoxicity was determined in the HeLa, HCT-116 and SW837 cancer cell lines; moderate CC50 (µM) values were seen from the mid-teens to no effect at 100 µM. Furthermore, citral derivative 20c, α-pinene-derived compounds 20f, 20g and 25c, and the citronellic acid derivative 25b were found to have a sensitizing effect in conjunction with topotecan in the HeLa cervical cancer and colon adenocarcinoma HCT-116 cell lines. The ligands are predicted to bind in the catalytic pocket of Tdp1 and have favorable physicochemical properties for further development as a potential adjunct therapy with Top1 poisons.

  酪氨酸-DNA磷酸二酯酶1（Tdp1）是抗癌治疗的一个有前途的靶点，因为它能够对抗拓扑异构酶1（Top1）毒素的影响，如托泊替康（topotecan），从而降低它们的疗效。含有金刚烷和单萜类残基，通过1,2,4-三唑或1,3,4-噻二唑连接剂连接的化合物已经合成并对Tdp1进行了测试。所有衍生物在低微摄或纳摄浓度下表现出抑制作用，其中最有效的抑制剂的IC50值在0.35-0.57 µM范围内。细胞毒性在HeLa、HCT-116和SW837癌细胞系中进行了测定；中等CC50（µM）值从中十几到100 µM无效不等。此外，在HeLa宫颈癌和结肠腺癌HCT-116细胞系中，柠檬醛衍生物20c，α-蒎烯衍生物20f、20g和25c，以及柠檬醛酸衍生物25b被发现与托泊替康联用具有增敏作用。 预测这些配体将结合在Tdp1的催化口袋中，并具有有利的物理化学性质，可进一步作为与Top1毒素联合治疗的潜在辅助疗法进行开发。