6-(benzyloxy)-1-naphthoic acid

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 6-(benzyloxy)-1-naphthoic acid
• 英文别名: 6-benzyloxy-1-naphthoic acid；6-Phenylmethoxynaphthalene-1-carboxylic acid
• 化学式: C₁₈H₁₄O₃
• 分子量: 278.307
• InChiKey: OJVPPVGIDCXECA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  6-(benzyloxy)-1-naphthoic acid 在 4-二甲氨基吡啶 、 10% palladium hydroxide on charcoal 、 氢气 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 12.0h， 生成 [(1R,3aR,4S,7aR)-7a-methyl-1-[(2R)-6-methylheptan-2-yl]-1,2,3,3a,4,5,6,7-octahydroinden-4-yl] 6-hydroxynaphthalene-1-carboxylate
  参考文献：
  名称：

  基于维生素D3的芳香A环类似物作为刺猬通路抑制剂的结构与活性之间的关系

  摘要：

  对一系列基于维生素D3（VD3）类似物的结构-活性关系的研究结合了功能不同的芳香族A环模拟物，提供了对脚手架特征的关键见解，这些特征可导致有效的，选择性的刺猬（Hh）途径抑制。制备并评估了三个类似的亚类，这些亚类包含（1）在芳族A-环的邻位或对位单取代，（2）杂芳基或联芳基部分或（3）在芳族A-环上的多个取代基。在六元环上掺入单个或多个亲水部分的芳香族A环模拟物在依赖Hh的小鼠胚胎成纤维细胞和培养的癌细胞中均抑制Hh途径（IC 50值0.74–10μM）。进行了初步研究以探究最活跃的类似物VD3和5抑制Hh信号传导的细胞机制。这些研究表明，VD3的抗Hh活性主要归因于维生素D受体，而5则通过单独的机制影响Hh抑制作用。

  DOI：

  10.1021/jm401812d
• 作为产物：
  描述：

  6-羟基-1-萘甲酸 在 氢氧化钾 、 sodium hydroxide 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 34.0h， 生成 6-(benzyloxy)-1-naphthoic acid
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationship of a Novel Series of Aminoalkylindoles with Potential for Imaging the Neuronal Cannabinoid Receptor by Positron Emission Tomography

  摘要：

  A new series of CB1 ligands with high binding affinity (K-i = 0.7-100 nM) and moderate lipophilicity (cLogD(7.4)) in the range of 2.1-4.5 has been synthesized. A structure-activity relationship study demonstrated that for the studied set of aminoalkylindoles, the molecular dipole of the ground state conformation within the series was inversely related to the affinity. The racemic ligand with highest affinity (0.7 nM), 3-(4-fluoronaphthoyl)-1-(N-methylpiperidin-2-ylmethyl)indole, was radiolabeled with F-18. This radioligand specifically labeled CB, receptors in mouse brain and accumulated in regions of high versus low CB1 receptor density in a ratio of 1.6. The displaceable radioactivity of one enantiomer in the brains of mice determined in a pretreatment study using the CB, antagonist N-(piperidinyl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (SR141716) was nearly double that of the racemate for the same determination; therefore, the active enantiomer is a candidate for PET studies in animals. A pretreatement study for the other enantiomer found no displaceable radioactivity in the same group of mice; this result suggested the enantiomer was inactive.

  DOI：

  10.1021/jm0502743

文献信息

• Enantioselective Rh-Catalyzed Azide-Internal-Alkyne Cycloaddition for the Construction of Axially Chiral 1,2,3-Triazoles
  作者：Wen-Ting Guo、Bo-Han Zhu、Yi Chen、Jian Yang、Peng-Cheng Qian、Chao Deng、Long-Wu Ye、Long Li

  DOI：10.1021/jacs.2c01985

  日期：2022.4.20

  achieved for the construction of chiral skeletons containing 1,2,3-triazoles via transition-metal-catalyzed asymmetric azide–alkyne cycloaddition; however, most of them have been limited to terminal alkynes in the synthesis of central chirality via desymmetrization and dynamic/dynamic kinetic resolution. Enantioselective transition-metal-catalyzed azide-internal-alkyne cycloaddition is extremely limited

  通过过渡金属催化的不对称叠氮化物-炔烃环加成，构建含有 1,2,3-三唑的手性骨架取得了重大进展；然而，它们中的大多数仅限于通过去对称化和动态/动态动力学拆分合成中心手性的末端炔烃。对映选择性过渡金属催化的叠氮化物-内炔环加成反应极为有限。此外，通过过渡金属催化的不对称叠氮化物-内-炔烃环加成构建具有挑战性的五元（杂）联芳基轴向手性分子仍处于探索阶段。在此，我们首先报告了轴向手性 1,4,5-三取代 1,2,3-三唑的阻转选择性和原子经济合成，直接作为具有挑战性的五元阻转异构体的核心手性单元，通过内部炔烃和叠氮化物的对映选择性Rh催化叠氮化物-炔烃环加成（E-RhAAC）。该反应表现出优异的官能团耐受性，在温和条件下以中等至优异的产率（高达 99% 产率）和通常高至优异的对映选择性（高达 99%）锻造各种 C–C 轴向手性 1,2,3-三唑ee) 以及特定的区域控制。密度泛函理论 (DFT)
• Construction of Bridged Benzazepines via Photo‐Induced Dearomatization
  作者：Ting‐Ting Song、Yong‐Kang Mei、Yan Liu、Xiao‐Yu Wang、Shi‐Yu Guo、Ding‐Wei Ji、Boshun Wan、Weiming Yuan、Qing‐An Chen

  DOI：10.1002/anie.202314304

  日期：2024.1.8

  A mild and efficient protocol is developed to convert simple aromatic substrates into value-added and structurally complex bridged benzazepines via a photocatalytic dearomatization. The switchable diastereoselectivity could be furnished by the manipulation of base-promoted or photoinduced intramolecular hydroamination.

  开发了一种温和有效的方案，通过光催化脱芳构化将简单的芳香族底物转化为增值且结构复杂的桥联苯并氮杂卓。可通过碱促进或光诱导的分子内氢氨化的操作来提供可切换的非对映选择性。
• Structure–Activity Relationships for Vitamin D3-Based Aromatic A-Ring Analogues as Hedgehog Pathway Inhibitors
  作者：Albert M. DeBerardinis、Daniel J. Madden、Upasana Banerjee、Vibhavari Sail、Daniel S. Raccuia、Daniel De Carlo、Steven M. Lemieux、Adam Meares、M. Kyle Hadden

  DOI：10.1021/jm401812d

  日期：2014.5.8

  A structure–activity relationship study for a series of vitamin D3-based (VD3) analogues that incorporate aromatic A-ring mimics with varying functionality has provided key insight into scaffold features that result in potent, selective Hedgehog (Hh) pathway inhibition. Three analogue subclasses containing (1) a single substitution at the ortho or para position of the aromatic A-ring, (2) a heteroaryl

  对一系列基于维生素D3（VD3）类似物的结构-活性关系的研究结合了功能不同的芳香族A环模拟物，提供了对脚手架特征的关键见解，这些特征可导致有效的，选择性的刺猬（Hh）途径抑制。制备并评估了三个类似的亚类，这些亚类包含（1）在芳族A-环的邻位或对位单取代，（2）杂芳基或联芳基部分或（3）在芳族A-环上的多个取代基。在六元环上掺入单个或多个亲水部分的芳香族A环模拟物在依赖Hh的小鼠胚胎成纤维细胞和培养的癌细胞中均抑制Hh途径（IC 50值0.74–10μM）。进行了初步研究以探究最活跃的类似物VD3和5抑制Hh信号传导的细胞机制。这些研究表明，VD3的抗Hh活性主要归因于维生素D受体，而5则通过单独的机制影响Hh抑制作用。
• Synthesis and Structure−Activity Relationship of a Novel Series of Aminoalkylindoles with Potential for Imaging the Neuronal Cannabinoid Receptor by Positron Emission Tomography
  作者：Peter G. Willis、Olga A. Pavlova、Svetlana I. Chefer、D. Bruce Vaupel、Alexey G. Mukhin、Andrew G. Horti

  DOI：10.1021/jm0502743

  日期：2005.9.1

  A new series of CB1 ligands with high binding affinity (K-i = 0.7-100 nM) and moderate lipophilicity (cLogD(7.4)) in the range of 2.1-4.5 has been synthesized. A structure-activity relationship study demonstrated that for the studied set of aminoalkylindoles, the molecular dipole of the ground state conformation within the series was inversely related to the affinity. The racemic ligand with highest affinity (0.7 nM), 3-(4-fluoronaphthoyl)-1-(N-methylpiperidin-2-ylmethyl)indole, was radiolabeled with F-18. This radioligand specifically labeled CB, receptors in mouse brain and accumulated in regions of high versus low CB1 receptor density in a ratio of 1.6. The displaceable radioactivity of one enantiomer in the brains of mice determined in a pretreatment study using the CB, antagonist N-(piperidinyl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (SR141716) was nearly double that of the racemate for the same determination; therefore, the active enantiomer is a candidate for PET studies in animals. A pretreatement study for the other enantiomer found no displaceable radioactivity in the same group of mice; this result suggested the enantiomer was inactive.