methyl 3-(benzyloxy)-2-naphthoate | 1054314-91-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: methyl 3-(benzyloxy)-2-naphthoate
• 英文别名: methyl 3-(benzyloxy)naphthalene-2-carboxylate；methyl 3-phenylmethoxynaphthalene-2-carboxylate
• CAS: 1054314-91-8
• 化学式: C₁₉H₁₆O₃
• 分子量: 292.334
• InChiKey: SEDTUTMASNHVMV-UHFFFAOYSA-N

物化性质

• 沸点：
  455.3±20.0 °C(predicted)
• 密度：
  1.187±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  methyl 3-(benzyloxy)-2-naphthoate 在 锂硼氢 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 以83%的产率得到(3-(benzyloxy)naphthalen-2-yl)methanol
  参考文献：
  名称：

  Novel Aldosterone Synthase Inhibitors with Extended Carbocyclic Skeleton by a Combined Ligand-Based and Structure-Based Drug Design Approach

  摘要：

  Pharmacophore modeling of a series of aldosterone synthase (CYP11B2) inhibitors triggered the design of compounds 11 and 12 by extending a previously established naphthalene molecular scaffold (e.g., present in molecules 1 and 2) via introduction of a phenyl or benzyl residue in 3-position. These additional aromatic moieties have been hypothesized to fit into the newly identified hydrophobic pharmacophore feature HY3. Subsequent docking studies in our refined CYP11B2 protein model have been performed prior to synthesis to estimate the inhibitory properties of the proposed molecules. While phenyl-substituted compound 11 (IC50 > 500 nM) did not dock under the given pharmacophore constraint (i.e., the Fe(heme)-N(ligand) interaction), benzyl-substituted compound 12 (IC50 = 154 nM) was found to exploit a previously unexplored subpocket of the inhibitor binding site. By structural optimization based on the pharmacophore hypothesis, 25 novel compounds were synthesized, among them highly potent CYP11B2 inhibitors (e.g., 17, IC50 = 2.7 nM) with pronounced selectivity toward the most important steroidogenic and hepatic CYP enzymes.

  DOI：

  10.1021/jm800683c
• 作为产物：
  描述：

  2-羟基-3-萘甲酸 在 硫酸 、 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 44.0h， 生成 methyl 3-(benzyloxy)-2-naphthoate
  参考文献：
  名称：

  动态不对称诱导制备对映体富集的螺旋和轴手性分子

  摘要：

  外消旋动态手性异螺旋烯的动态不对称诱导 (DYASIN) 以定量产率提供了它们高度对映体富集的形式（高达 96% ep）。这些异螺旋烯很容易以立体定向的方式转化为半静态轴向手性 1,1'-联萘衍生物。

  DOI：

  10.1039/d1cc05881a

文献信息

• Metal-Free C–O Bond Functionalization: Catalytic Intramolecular and Intermolecular Benzylation of Arenes
  作者：Luis Bering、Kirujan Jeyakumar、Andrey P. Antonchick

  DOI：10.1021/acs.orglett.8b01495

  日期：2018.7.6

  conditions enabled a catalytic and metal-free Friedel–Crafts alkylation reaction with benzylic alcohols, producing water as the stoichiometric byproduct. A comprehensive scope (>50 examples) for both approaches and application in drug synthesis were demonstrated. Mechanistic studies suggest a Lewis acid-based mechanism for the metal-free Friedel–Crafts reaction.

  描述了使用硝鎓盐作为催化剂的苄基苯基醚的无金属催化的分子内重排。优化的反应条件使苄基醇能够进行无金属催化的Friedel-Crafts烷基化反应，从而产生水作为化学计量副产物。展示了方法和在药物合成中的应用的综合范围（> 50个示例）。机理研究表明，路易斯酸基机理可用于无金属的Friedel-Crafts反应。
• Novel Aldosterone Synthase Inhibitors with Extended Carbocyclic Skeleton by a Combined Ligand-Based and Structure-Based Drug Design Approach
  作者：Simon Lucas、Ralf Heim、Matthias Negri、Iris Antes、Christina Ries、Katarzyna E. Schewe、Alessandra Bisi、Silvia Gobbi、Rolf W. Hartmann

  DOI：10.1021/jm800683c

  日期：2008.10.9

  Pharmacophore modeling of a series of aldosterone synthase (CYP11B2) inhibitors triggered the design of compounds 11 and 12 by extending a previously established naphthalene molecular scaffold (e.g., present in molecules 1 and 2) via introduction of a phenyl or benzyl residue in 3-position. These additional aromatic moieties have been hypothesized to fit into the newly identified hydrophobic pharmacophore feature HY3. Subsequent docking studies in our refined CYP11B2 protein model have been performed prior to synthesis to estimate the inhibitory properties of the proposed molecules. While phenyl-substituted compound 11 (IC50 > 500 nM) did not dock under the given pharmacophore constraint (i.e., the Fe(heme)-N(ligand) interaction), benzyl-substituted compound 12 (IC50 = 154 nM) was found to exploit a previously unexplored subpocket of the inhibitor binding site. By structural optimization based on the pharmacophore hypothesis, 25 novel compounds were synthesized, among them highly potent CYP11B2 inhibitors (e.g., 17, IC50 = 2.7 nM) with pronounced selectivity toward the most important steroidogenic and hepatic CYP enzymes.
• Preparation of enantioenriched helical- and axial-chiral molecules by dynamic asymmetric induction
  作者：Yuuya Kawasaki、Ryota Kamikubo、Yuta Kumegawa、Kouhei Ogawa、Takeru Kashiwagi、Yusuke Ano、Kazunobu Igawa、Katsuhiko Tomooka

  DOI：10.1039/d1cc05881a

  日期：——

  Dynamic asymmetric induction (DYASIN) of racemic dynamic chiral heterohelicenes afforded their highly enantioenriched forms (up to 96% ep) in quantitative yields. These heterohelicenes were readily converted into semi-static axial-chiral 1,1′-binaphthyl derivatives in a stereospecific manner.

  外消旋动态手性异螺旋烯的动态不对称诱导 (DYASIN) 以定量产率提供了它们高度对映体富集的形式（高达 96% ep）。这些异螺旋烯很容易以立体定向的方式转化为半静态轴向手性 1,1'-联萘衍生物。