3,4,5-(trimethoxyphenyl)(naphthalen-6-yl)methanol | 945034-28-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 3,4,5-(trimethoxyphenyl)(naphthalen-6-yl)methanol
• 英文别名: (2-naphthyl)(3,4,5-trimethoxyphenyl)methanol；naphthalen-2-yl(3,4,5-trimethoxyphenyl)methanol；Naphthalen-2-yl-(3,4,5-trimethoxyphenyl)methanol
• CAS: 945034-28-6
• 化学式: C₂₀H₂₀O₄
• 分子量: 324.376
• InChiKey: QYYYZSCQXIREHN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  47.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3,4,5-(trimethoxyphenyl)(naphthalen-6-yl)methanol 以 二氯甲烷 为溶剂， 生成 naphthalen-2-yl(3,4,5-trimethoxyphenyl)methanone
  参考文献：
  名称：

  异combretastatins A：1，1-二芳烃作为微管蛋白聚合和细胞毒性化合物的有效抑制剂

  摘要：

  异combretastatins A是康美他汀A的1,1-二芳基乙烯异构体。我们合成了combrestastatin A-4，脱氧康布他汀A-4、3-氨基-脱氧康布他汀A-4（AVE-8063），萘基康布他汀A和N-甲基-和康布雷他汀A-4的N-乙基-5-吲哚基类似物。还已经制备了具有2,3,4-三甲氧基苯基环而不是3,4,5-三甲氧基苯基环的类似物。异combretastatins A强烈抑制微管蛋白聚合，并且是有效的细胞毒性化合物，其中一些具有IC 50在纳摩尔范围内。与酚他汀或康维他汀类似物相比，这个新的微管蛋白抑制剂家族显示出更高或相当的效力。这些结果表明，具有双芳基双取代的一个碳桥可以成功地替代康美他汀的两个碳桥，并且苯他汀类的羰基对于高效能并不是必不可少的。

  DOI：

  10.1016/j.bmc.2009.07.012
• 作为产物：
  描述：

  2-溴萘 、 3,4,5-三甲氧基苯甲醛 在 正丁基锂 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 1.0h， 生成 3,4,5-(trimethoxyphenyl)(naphthalen-6-yl)methanol
  参考文献：
  名称：

  异combretastatins A：1，1-二芳烃作为微管蛋白聚合和细胞毒性化合物的有效抑制剂

  摘要：

  异combretastatins A是康美他汀A的1,1-二芳基乙烯异构体。我们合成了combrestastatin A-4，脱氧康布他汀A-4、3-氨基-脱氧康布他汀A-4（AVE-8063），萘基康布他汀A和N-甲基-和康布雷他汀A-4的N-乙基-5-吲哚基类似物。还已经制备了具有2,3,4-三甲氧基苯基环而不是3,4,5-三甲氧基苯基环的类似物。异combretastatins A强烈抑制微管蛋白聚合，并且是有效的细胞毒性化合物，其中一些具有IC 50在纳摩尔范围内。与酚他汀或康维他汀类似物相比，这个新的微管蛋白抑制剂家族显示出更高或相当的效力。这些结果表明，具有双芳基双取代的一个碳桥可以成功地替代康美他汀的两个碳桥，并且苯他汀类的羰基对于高效能并不是必不可少的。

  DOI：

  10.1016/j.bmc.2009.07.012

文献信息

• Carbon-Based Leaving Group in Substitution Reactions: Functionalization of sp³-Hybridized Quaternary and Tertiary Benzylic Carbon Centers
  作者：Stuart J. Mahoney、Tiantong Lou、Ganna Bondarenko、Eric Fillion

  DOI：10.1021/ol301442z

  日期：2012.7.6

  Lewis acid promoted substitution reactions employing Meldrum’s acid and 5-methyl Meldrum’s acid as carbon-based leaving groups are described which transform unstrained quaternary and tertiary benzylic Csp3–Csp3 bonds into Csp3–X bonds (X = C, H, N). Importantly, this reaction has a broad scope in terms of both suitable substrates and nucleophiles with good to excellent yields obtained (typically >90%)

  描述了路易斯酸促进的取代反应，该反应使用Meldrum酸和5-甲基Meldrum酸作为碳基离去基团，可将未应变的季铵和叔苄基C sp 3 –C sp 3键转变为C sp 3 –X键（X = C，H ，N）。重要的是，就合适的底物和亲核试剂而言，该反应具有广泛的范围，并具有良好至优异的产率（通常＞ 90％）。
• Chiral Iridium Complexes of Anionic NCP Pincer Ligand for Asymmetric Transfer Hydrogenation of 1,1-Diarylethenes with Ethanol
  作者：Lu Qian、Xixia Tang、Zhidao Huang、Yulei Wang、Guixia Liu、Zheng Huang

  DOI：10.1021/acs.orglett.1c03455

  日期：2021.11.19

  Chiral iridium complexes ligated by anionic oxazoline-bearing NCP-type pincer ligands were developed and applied to the asymmetric transfer hydrogenation (ATH) of diarylethenes using environmentally benign ethanol as the hydrogen donor. High enantioselectivities could be achieved for substrates bearing ortho-Me, ortho-Cl, or ortho-Br substituents on one of the aryl groups. The ATH of ortho-Br-substituted

  开发了由带有阴离子恶唑啉的 NCP 型钳形配体连接的手性铱配合物，并将其应用于使用环境友好型乙醇作为氢供体的二芳基乙烯的不对称转移氢化 (ATH)。对于在芳基之一上带有邻-Me、邻-Cl或邻-Br取代基的底物可以实现高对映选择性。由于 C （芳基） -Br 键易于经历各种新的键形成事件，邻位-Br 取代的二芳基乙烯的 ATH特别有吸引力。
• Stereospecific Nickel-Catalyzed Cross-Coupling Reactions of Benzylic Ethers with Isotopically-Labeled Grignard Reagents
  作者：David D. Dawson、Elizabeth R. Jarvo

  DOI：10.1021/acs.oprd.5b00148

  日期：2015.10.16

  we highlight the potential of stereospecific nickel-catalyzed cross-coupling reactions for applications in the pharmaceutical industry. Using an inexpensive and sustainable nickel catalyst, we report a gram-scale Kumada cross-coupling reaction. Reactions are highly stereospecific and proceed with inversion at the benzylic position. We also expand the scope of our reaction to incorporate isotopically

  在本手稿中，我们重点介绍了在制药行业中应用的立体定向镍催化的交叉偶联反应的潜力。我们使用一种廉价且可持续的镍催化剂，报道了克级的熊田交叉偶联反应。反应具有高度立体特异性，并在苄基位置进行转化。我们还扩大了反应范围，以掺入同位素标记的取代基。
• Synthesis and biological activity of naphthalene analogues of phenstatins: Naphthylphenstatins
  作者：Concepción Álvarez、Raquel Álvarez、Purificación Corchete、Concepción Pérez-Melero、Rafael Peláez、Manuel Medarde

  DOI：10.1016/j.bmcl.2007.03.082

  日期：2007.6

  Novel phenstatin analogues with a 2-naphthyl moiety combined with either a 2,3,4- or a 3,4,5-trimethoxyphenyl ring have been synthesized, and their tubulin polymerization inhibiting and cytotoxic activities have been evaluated. The 2-naphthyl ring is a better replacement for the 3-hydroxy-4-methoxyphenyl ring in the phenstatin series than in the combretastatin series. For the naphthylphenstatins, the carbonyl is required, and the preferred orientation of the trimethoxyphenyl ring is the one found in combretastatins. (c) 2007 Elsevier Ltd. All rights reserved.
• Naphthylphenstatins as tubulin ligands: Synthesis and biological evaluation
  作者：Concepción Álvarez、Raquel Álvarez、Purificación Corchete、Concepción Pérez-Melero、Rafael Peláez、Manuel Medarde

  DOI：10.1016/j.bmc.2008.08.040

  日期：2008.10

  A new family of naphthalenic analogues of phenstatins with modi. cations on the ketone-bridge has been synthesised. The synthesised compounds have been assayed for tubulin polymerisation inhibitory activity as well as for cytotoxic activity against cancer cell lines. The naphthalene has been confirmed as a good surrogate for the isovanillin moiety (3-hydroxy-4-methoxyphenyl) of phenstatin, when combined with the 3,4,5-trimethoxyphenyl ring, but not when combines with the 2,3,4-trimethoxyphenyl ring. Binding models for the synthesised compounds have been generated and analysed in terms of a pharmacophore proposed for colchicine site ligands. The ketone is the optimal bridge substitution but E-acetyloximes or acetylhydrazones are also tolerated. Significant differences with indole substituted phenstatins are observed and discussed. (C) 2008 Published by Elsevier Ltd.