3,5-dibenzyloxy-4-methoxybenzoic acid | 19859-90-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 3,5-dibenzyloxy-4-methoxybenzoic acid
• 英文别名: 3,5-Dibenzyloxy-4-methoxybenzoesaeure；3,5-Bis(benzyloxy)-4-methoxybenzoic acid；4-methoxy-3,5-bis(phenylmethoxy)benzoic acid
• CAS: 19859-90-6
• 化学式: C₂₂H₂₀O₅
• 分子量: 364.398
• InChiKey: PMZDWSGWYVHWMV-UHFFFAOYSA-N

物化性质

• 熔点：
  173 °C
• 沸点：
  533.8±45.0 °C(Predicted)
• 密度：
  1.233±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  27
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  65
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3,5-dibenzyloxy-4-methoxybenzoic acid 在 草酰氯 、 lithium diisopropyl amide 作用下， 以 N,N-二甲基甲酰胺 、 苯 为溶剂， 反应 1.92h， 生成 Ethyl 3-[4-methoxy-3,5-bis(phenylmethoxy)phenyl]-3-oxopropanoate
  参考文献：
  名称：

  Synthesis and PAF antagonist activity of some 2,5-diaryltetrahydrofurans incorporating PAF-like functional groups

  摘要：

  This paper describes the synthesis and structure-activity relationships of a series of 2,5-diaryltetrahydrofurans, as specific and potent antagonists at the rabbit washed platelet activating factor (PAF) receptor. The methoxyl groups in the known PAF antagonist L-652,731 were replaced with functional groups present in PAF and in the 'PAF-like' antagonists. Activity was generally retained or enhanced when one aryl ring in L-652,731 was elaborated; however incorporation of these functional groups into both of the aryl rings greatly reduced or abolished activity. These results are discussed in relation to a putative model for the PAF receptor.

  DOI：

  10.1016/0223-5234(96)89161-6
• 作为产物：
  描述：

  没食子酸甲酯 在 potassium carbonate 、 caesium carbonate 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 65.5h， 生成 3,5-dibenzyloxy-4-methoxybenzoic acid
  参考文献：
  名称：

  生物启发的Bussealin E的全合成

  摘要：

  据报道，具有独特的环庚二苯并呋喃支架的天然产物bussealin E的第一个全合成。采用了一种受提议的生物合成启发的策略，其中二苯丙烷衍生物经过氧化酚偶联以形成四环系统。二苯丙烷的合成具有乙烯基二硅氧烷和苄基溴之间的关键sp 2 –sp 3 Hiyama偶联。

  DOI：

  10.1021/acs.orglett.8b00340

文献信息

• N,N'-Heptamethylenebis(4-methoxybenzamide)
  申请人：Sterling Drug Inc.

  公开号：US04009208A1

  公开（公告）日：1977-02-22

  4-(Q-O)-4'-R.sub.1 -N,N'-alkylenebis(benzamides), N,N'-alkylenebis(3,4-methylenedioxybenzamides) or N,N'-alkylenebis[4-(lower-alkoxy)benzamides], having endocrinological properties, where Q is lower-alkyl, lower-alkoxyalkyl, lower-alkenyl, halo-lower-alkyl, halo-lower-alkenyl, lower-cycloalkyl, phenyl and BN-(lower-alkyl) where BN is di-(lower-alkyl)amino or a saturated N-heteromonocyclic radical having from five to seven ring atoms and alkylene has at least five carbon atoms between its two connecting linkages and R.sub.1 is Q-O-, hydrogen, lower-alkoxy, lower-alkyl, halo, benzyloxy, hydroxy, di-(lower-alkyl)amino, nitro, amino or trihalomethyl are prepared preferably by reacting the appropriate diamine or N-(aminoalkyl)-benzamide with two or one molar equivalents, respectively, of the appropriate benzoyl halide.

  4-(Q-O)-4'-R.sub.1 -N,N'-烷基亚苯二酰胺，N,N'-烷基亚苯二酰胺或N,N'-烷基亚苯二酰胺[4-(较低烷氧基)苯二酰胺]，具有内分泌学性质，其中Q为较低烷基，较低烷氧基烷基，较低烯基，卤代较低烷基，卤代较低烯基，较低环烷基，苯基和BN-(较低烷基)，其中BN为二(较低烷基)氨基或具有五至七个环原子的饱和N-杂环烷基基团，烷基在其两个连接链之间至少有五个碳原子，R.sub.1为Q-O-，氢，较低烷氧基，较低烷基，卤素，苄氧基，羟基，二(较低烷基)氨基，硝基，氨基或三卤甲基，最好通过将适当的二胺或N-(氨基烷基)-苯二酰胺与相应的苯甲酰卤反应制备两个或一个摩尔当量。
• Total synthesis of (±)-megistophylline I
  作者：Yuko Nishihama、Yuichi Ishikawa、Shigeru Nishiyama

  DOI：10.1016/j.tetlet.2009.03.157

  日期：2009.6

  (+/-)-Megistophylline I (1), carrying a dienone residue in the acridone framework, was synthesized using, the Claisen rearrangement to introduce a prenyl group as a key step. (C) 2009 Elsevier Ltd. All rights reserved.

  (±)-Megistophylline I（1）在吖啶酮骨架中含有二烯酮基团，其合成过程采用了Claisen重排反应作为关键步骤，以引入甲基丁烯基团。版权©2009 Elsevier Ltd. 保留所有权利。
• Solid-Phase Synthesis of a Combinatorial Methylated (±)-Epigallocatechin Gallate Library and the Growth-Inhibitory Effects of these Compounds on Melanoma B16 Cells
  作者：Hiroshi Tanaka、Maasa Yamanouchi、Haruko Miyoshi、Keisuke Hirotsu、Hirofumi Tachibana、Takashi Takahashi

  DOI：10.1002/asia.201000372

  日期：——

  We report on the solid‐phase synthesis of a combinatorial methylated (±)‐epigallocatechin gallate (EGCG) library and its biological evaluation. Epigallocatechin gallate (EGCG) and its methylated derivatives, which are members of the catechin family, exhibit various anti‐cancer effects. The solid‐phase synthesis of methylated EGCG involves the preparation of the α‐acyloxyketone by the coupling of a

  我们报告了组合甲基化（±）-表没食子儿茶素没食子酸酯（EGCG）库的固相合成及其生物学评估。儿茶素家族的成员表没食子儿茶素没食子酸酯（EGCG）及其甲基化衍生物具有多种抗癌作用。甲基化EGCG的固相合成涉及通过固相负载的醛与酮和酸的偶联来制备α-酰氧基酮。固体负载的α-酰氧基酮的后续释放和还原醚化反应以良好的总收率提供了受保护的EGCG。成功制备了64种甲基化EGCG。还检查了甲基化EGCG文库的生长抑制作用。尽管EGCG的甲基化通常会导致生长抑制作用降低，7-OMe EGCG的生长抑制作用与EGCG相当。7-OMe EGCG由于具有更高的生物利用度，因此是有吸引力的候选药物。
• Synthesis, crystal structure, and growth inhibition of human hepatoma cell (HepG2) of polyphenolic compounds based on gallates
  作者：Zhu-Ping Xiao、Rui-Qin Fang、Lei Shi、Hui Ding、Chen Xu、Hai-Liang Zhu

  DOI：10.1139/v07-107

  日期：2007.11.1

  Seven compounds (1–7) based on gallate were synthesized and characterized by elemental analysis, ¹H NMR, and MS spectra. 2-(3,5-Dibenzyloxy-4-methoxy)phenyl-2-propanol (6) was a new compound. Methyl 3,5-dihydroxy-4-methoxybenzoate (3), methyl 3,5-dibenzyloxy-4-methoxybenzoate (4), 3,5-dibenzyloxy-4-methoxybenzyl alcohol (5), and compound 6 were structurally determined by single-crystal X-ray diffraction for the first time. Crystallographic data for 3: space group P2₁2₁2₁; a = 4.0750(8) Å, b = 7.5880(15) Å, c = 29.802(6) Å; V = 921.5(3) ų; Z = 4. 4: space group P-1; a = 10.068(2) Å, b = 10.499(2) Å, c = 11.388(2) Å; α = 76.84(3)°, β = 66.79(3)°, γ = 64.10(3)°; V = 993.0(3) ų, Z = 2. 5: space group P-1; a = 8.1410(16) Å, b = 8.7590(18) Å, c = 12.879(3) Å; α = 91.66(3)°, β = 94.69(3)°, γ = 91.73(3)°; V = 914.4(3) ų; Z = 2. 6: space group P2₁/c; a = 5.8100(12) Å, b = 15.778(3) Å, c = 23.237(5) Å; β = 96.09(3)°; V = 2118.1(7) ų; Z = 4. All of the seven compounds were evaluated for the inhibition of growth of human hepatoma (HepG2) cells. Comparison with the positive-control 5-fluorouracil (IC₅₀ 51.6 µmol/L), 5 showed stronger cytotoxic activity with an IC₅₀ around 15.3 µmol/L, while IC₅₀ value of 3 was 90.3 µmol/L. The effect of slight structural variations in this series of compounds was found to cause a marked change in their activity against HepG2 cells.Key words: gallates, benzyl alcohol, human hepatoma cells, crystal structure, anti-cancer activities.

  合成了七种基于没食子酸酯的化合物（1-7），并通过元素分析、1H NMR 和 MS 光谱对其进行了表征。2-(3,5-二苄氧基-4-甲氧基)苯基-2-丙醇（6）是一种新化合物。首次通过单晶 X 射线衍射测定了 3,5-二羟基-4-甲氧基苯甲酸甲酯（3）、3,5-二苄氧基-4-甲氧基苯甲酸甲酯（4）、3,5-二苄氧基-4-甲氧基苯甲醇（5）和化合物 6 的结构。3 的晶体数据：空间群 P212121；a = 4.0750(8) Å，b = 7.5880(15) Å，c = 29.802(6) Å；V = 921.5(3) Å3；Z = 4。4：空间群 P-1；a = 10.068(2)埃，b = 10.499(2)埃，c = 11.388(2)埃；α = 76.84(3)°，β = 66.79(3)°，γ = 64.10(3)°；V = 993.0(3) Å3，Z = 2。5：空间群 P-1；a = 8.1410(16) Å，b = 8.7590(18) Å，c = 12.879(3) Å；α = 91.66(3)°，β = 94.69(3)°，γ = 91.73(3)°；V = 914.4(3) Å3；Z = 2。6：空间群 P21/c；a = 5.8100(12)埃，b = 15.778(3)埃，c = 23.237(5)埃；β = 96.09(3)°；V = 2118.1(7)埃3；Z = 4。对所有七种化合物抑制人肝癌（HepG2）细胞生长的能力进行了评估。与阳性对照 5-氟尿嘧啶（IC50 51.6 µmol/L）相比，5 显示出更强的细胞毒性活性，IC50 约为 15.3 µmol/L，而 3 的 IC50 值为 90.3 µmol/L。在这一系列化合物中，发现轻微的结构变化会导致它们对 HepG2 细胞的活性发生显著变化。
• The Synthesis of Methylated Epigallocatechin Gallate
  作者：Ronghui Lai、Wenfang Zhao、Yahui Huang、Wen Zhou、Chunlan Wu、Xingfei Lai、Wenxia Zhao、Ming Zhang

  DOI：10.1007/s10600-015-1317-5

  日期：2015.5

  Synthesis of methylated epigallocatechin gallate from (–)-epigallocatechin gallate and propylgallate was accomplished using a benzyl (Bn) group as a protecting group for phenols. This methodology provided (–)-epigallocatechin-3-(4-O-methylgallate), which are naturally scarce catechin derivatives.

  使用苄基 (Bn) 基团作为苯酚的保护基团，从 (–)-表没食子儿茶素没食子酸酯和没食子酸丙酯合成甲基化表没食子儿茶素没食子酸酯。该方法提供了 (–)-表没食子儿茶素-3-(4-O-甲基没食子酸酯)，它是天然稀缺的儿茶素衍生物。