2-(3,4-二甲氧基苯基)-1-(2,3,4-三羟基苯基)乙酮 | 93435-58-6

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二苯乙烯类
• 中文名称: 2-(3,4-二甲氧基苯基)-1-(2,3,4-三羟基苯基)乙酮
• 英文名称: 2,3,4-trihydroxy-3',4'-dimethoxydeoxybenzoin
• 英文别名: 2-(3,4-dimethoxyphenyl)-1-(2,3,4-trihydroxyphenyl)ethanone；<2,3,4-Trihydroxy-phenyl>-<3,4-dimethoxy-benzyl>-keton；1-(2,3,4-trihydroxyphenyl)-2-(3',4'-dimethoxyphenyl)ethanone；2-(3,4-Dimethoxyphenyl)-1-(2,3,4-trihydroxyphenyl)ethan-1-one
• CAS: 93435-58-6
• 化学式: C₁₆H₁₆O₆
• 分子量: 304.299
• InChiKey: ZINQWXFFXBTZOW-UHFFFAOYSA-N

物化性质

• 熔点：
  174°C
• 沸点：
  536.2±50.0 °C(Predicted)
• 密度：
  1.352±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  96.2
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-(3,4-二甲氧基苯基)-1-(2,3,4-三羟基苯基)乙酮 在 吡啶 、 三氟化硼乙醚 、 甲基磺酰氯 作用下， 生成 7,8-diacetoxy-3',4'-dimethoxyisoflavone
  参考文献：
  名称：

  异黄酮的氧化二聚：葛根黄酮A及其相关化合物的合成*

  摘要：

  Kudzuisoflavone-A是在氯化亚铜存在下通过大豆苷元的氧化二聚作用成功合成的。当用三氟乙酸th处理时，适当取代的异黄酮也进行区域选择性氧化二聚，从而以高收率得到新的6'，6'''-二异黄酮。提出了区域选择性的基本原理。

  DOI：

  10.1071/ch12108
• 作为产物：
  描述：

  在 盐酸 、 水 作用下， 生成 2-(3,4-二甲氧基苯基)-1-(2,3,4-三羟基苯基)乙酮
  参考文献：
  名称：

  Enzymatic Studies of Isoflavonoids as Selective and Potent Inhibitors of Human Leukocyte 5-Lipo-Oxygenase

  摘要：

  Continuing our search to find more potent and selective 5‐LOX inhibitors, we present now the enzymatic evaluation of seventeen isoflavones (IR) and nine isoflavans (HIR), and their in vitro and in cellulo potency against human leukocyte 5‐LOX. Of the 26 compounds tested, 10 isoflavones and 9 isoflavans possessed micromolar potency, but only three were selective against 5‐LOX (IR‐2, HIR‐303, and HIR‐309), with IC50 values at least 10 times lower than those of 12‐LOX, 15‐LOX‐1, and 15‐LOX‐2. Of these three, IR‐2 (6,7‐dihydroxy‐4‐methoxy‐isoflavone, known as texasin) was the most selective 5‐LOX inhibitor, with over 80‐fold potency difference compared with other isozymes; Steered Molecular Dynamics (SMD) studies supported these findings. The presence of the catechol group on ring A (6,7‐dihydroxy versus 7,8‐dihydroxy) correlated with their biological activity, but the reduction of ring C, converting the isoflavones to isoflavans, and the substituent positions on ring B did not affect their potency against 5‐LOX. Two of the most potent/selective inhibitors (HIR‐303 and HIR‐309) were reductive inhibitors and were potent against 5‐LOX in human whole blood, indicating that isoflavans can be potent and selective inhibitors against human leukocyte 5‐LOX in vitro and in cellulo.

  DOI：

  10.1111/cbdd.12469

文献信息

• The synthesis, structure and activity evaluation of pyrogallol and catechol derivatives as Helicobacter pylori urease inhibitors
  作者：Zhu-Ping Xiao、Tao-Wu Ma、Wei-Chang Fu、Xiao-Chun Peng、Ai-Hua Zhang、Hai-Liang Zhu

  DOI：10.1016/j.ejmech.2010.08.015

  日期：2010.11

  Some pyrogallol and catechol derivatives were synthesized, and their urease inhibitory activity was evaluated by using acetohydroxamic acid (AHA), a well known Helicobacter pylori urease inhibitor, as positive control. The assay results indicate that many compounds have showed potential inhibitory activity against H. pylori urease. 4-(4-Hydroxyphenethyl)phen-1,2-diol (2a) was found to be the most potent

  合成了一些邻苯三酚和邻苯二酚衍生物，并使用众所周知的幽门螺杆菌脲酶抑制剂乙酰氧肟酸（AHA）作为阳性对照，评估了它们对脲酶的抑制活性。测定结果表明许多化合物已显示出对幽门螺杆菌脲酶的潜在抑制活性。已发现4-（4-羟基苯乙基）phen-1,2-二醇（2a）是最有效的脲酶抑制剂，提取分数的IC 50值为1.5±0.2μM，完整细胞的IC 50值为4.2±0.3μM，至少10分别比AHA低2倍和20倍（IC 50为17.2±0.9μM，100.6±13μM）。这一发现表明2a潜在的脲酶抑制剂将值得进一步研究。为了理解所观察到的良好活性，进行了2a到幽门螺杆菌脲酶活性位点的分子对接。
• Synthesis of Various Kinds of Isoflavones, Isoflavanes, and Biphenyl-Ketones and Their 1,1-Diphenyl-2-picrylhydrazyl Radical-Scavenging Activities
  作者：Hideyuki Goto、Yoshiyasu Terao、Shuji Akai

  DOI：10.1248/cpb.57.346

  日期：——

  Forty-eight kinds of isoflavones (8), thirty-one isoflavanes (9), and forty-seven biphenyl-ketones (10, 10′) were synthesized from eleven kinds of substituted phenols (11) and six phenylacetic acids (12). Among them, seventy-five compounds are new. The radical scavenging activities of these compounds were evaluated using 1,1-diphenyl-2-picrylhydrazyl (DPPH) at pH 6.0. We found that thirty-nine out of forty-three compounds having a catechol moiety on either the A- or the B-ring exhibited a high activity (ED50=12—54 μM) similar to that of catechin. In these cases, the remaining part of their structure seemed to have little effect on their activity. Many 6- or 8-hydroxyisoflavanes (9E—I) and their biphenyl-ketone derivatives (10E—H) also showed a high activity (ED50=<50 μM), while all of their corresponding isoflavones (8E—I) were not active at all. The 7-hydroxyisoflavanes having either an additional hydroxyl group at the C5-position (9D) or a methoxy group at the C6-position (9J) presented a high activity (ED50=26—32 μM). This study suggests that natural isoflavones have the possibilities of exhibiting antioxidant activities through the hydroxylation at the C6-, C8-, or C3′-position or the formation of the isoflavanes (9) and/or the biphenyl-ketone derivatives (10′) by metabolism or biotransformation.

  合成了四十八种异黄酮（8）、三十一种异黄烷（9）以及四十七种联苯酮（10, 10′），这些化合物是由十一种取代酚（11）和六种苯乙酸（12）合成的。其中，有七十五种化合物是新发现的。这些化合物的自由基清除活性在pH 6.0下使用1,1-二苯基-2-吡唑啉酮（DPPH）进行了评估。我们发现，在四十三种含有儿茶酚基的化合物中，三十九种在A环或B环上表现出与儿茶素相似的高活性（ED50=12—54 μM）。在这些情况下，它们结构的其他部分似乎对活性影响不大。许多6-或8-羟基异黄烷（9E—I）及其联苯酮衍生物（10E—H）也显示出高活性（ED50=<50 μM），而它们对应的异黄酮（8E—I）则完全没有活性。具有在C5位增加羟基（9D）或在C6位增加甲氧基（9J）的7-羟基异黄烷则展现出高活性（ED50=26—32 μM）。本研究表明，天然异黄酮通过在C6、C8或C3′位置的羟基化，或通过代谢或生物转化形成异黄烷（9）和/或联苯酮衍生物（10′），具有表现抗氧化活性的可能性。
• Synthesis, biological evaluation and structure-activity relationship of a novel class of PI3Kα H1047R mutant inhibitors
  作者：Ning Zhang、Zhimei Yu、Xiaohong Yang、Yan Zhou、Jia Wang、Shao-Lin Zhang、Ming-Wei Wang、Yun He

  DOI：10.1016/j.ejmech.2018.09.002

  日期：2018.10

  treatment. As our continuing endeavor to discover isoform and/or mutant selective class of PI3K inhibitors, herein we report the optimization of a structurally novel PI3Kα H1047R mutant inhibitor Hit-02 (EC50 = 115.3 μM), which was identified from a high-throughput screening campaign. Structure-activity relationship analysis enabled us to discover compound 7h, which strongly inhibited PI3Kα H1047R

  磷脂酰肌醇3-激酶α（PI3Kα）是最有吸引力的癌症治疗靶标之一。作为我们不断努力发现PI3K抑制剂的同工型和/或突变体选择性类别的方法，我们在此报告了对结构新颖的PI3KαH1047R突变体抑制剂Hit-02（EC 50  = 115.3μM）的优化，该结构已通过高通量筛选确定活动。结构-活性关系分析使我们能够发现化合物7h，该化合物强烈抑制PI3KαH1047R突变体，其EC 50值为0.55μM ，效力比Hit-02高200倍以上，而对其他PI3K亚型的影响很小。Western blotting检测表明7h降低AKT的磷酸化水平，这是7h抑制PI3KαH1047R突变体功能的另一个证据。细胞活力测定显示7h抑制HCT-116癌细胞的生长，IC 50值为10.9μM。另外，发现7h使细胞周期停滞在G2期，但未显示任何细胞凋亡作用。此外，7h明显诱导细胞自噬，可能有助于其在癌细胞中的抗增
• Potential antioxidants and tyrosinase inhibitors from synthetic polyphenolic deoxybenzoins
  作者：Lean-Teik Ng、Horng-Huey Ko、Tzy-Ming Lu

  DOI：10.1016/j.bmc.2009.05.019

  日期：2009.7

  Deoxybenzoins (DOBs) are one-pot synthetic precursors of isoflavones with feature analogous to those beneficial polyphenols such as resveratrol (stilbene) and phloretin (dihydrochalcone). In this study, seventeen polyphenolic DOBs were synthesized and evaluated by various antioxidant assays and tyrosinase inhibitory effect in vitro. Results displayed that these DOBs are powerful antioxidants; for example, 2,3,4-trihydroxy-3',4'-dimethoxydeoxybenzoin possesses an excellent anti-lipid peroxidation activity (IC50 = 0.72 +/- 0.16 mu M), whilst 2,4,4',5-tetrahydroxydeoxybenzoin showed good DPPH radical scavenging activity (IC50 = 0.69 +/- 0.04 mu M), which were better than Trolox and vitamin C. Besides exhibiting a weak metal chelating effect, these DOBs were effective in scavenging ABTS(center dot+) and superoxide anion (O-2(center dot-)) radicals. DOBs also exhibited potent mushroom tyrosinase inhibitory activity; for example 2,3,4'-trihydroxy4- methoxydeoxybenzoin displayed stable and significant inhibitory effect on tyrosinase activity, with IC50 values 43.37, 43.10 and 46.10 mu M at incubation intervals of 0.5, 1.5, and 2.5 h, respectively. These results suggest that, with the advantage of being readily synthesizable small molecules, DOBs can be potentially developed into clinical and industrial antioxidants. Crown Copyright (C) 2009 Published by Elsevier Ltd. All rights reserved.
• Synthesis and Structure−Activity Relationship Study of Deoxybenzoins on Relaxing Effects of Porcine Coronary Artery
  作者：Tzy-Ming Lu、Daih-Huang Kuo、Horng-Huey Ko、Lean-Teik Ng

  DOI：10.1021/jf1023643

  日期：2010.9.22

  Deoxybenzoins are potent antioxidants and tyrosinase inhibitors with potential to be developed as food preservatives and cosmetic ingredients. To explore the potential in cardiovascular protection, 25 polyphenolic deoxybenzoins were synthesized and evaluated for inhibitory effects on KCl-induced porcine coronary arterial contraction. The results revealed deoxybenzoins are significant inhibitors of KCl-induced arterial contraction. Among those synthesized, two-thirds of the deoxybenzoins exhibited moderate to good efficacy on relaxing contracted artery including 2,4-dihydroxydeoxybenzoin with EC(50) = 3.30 mu M (E(max) = 100%, n = 7) and 2,4-dihydroxy-4'-methoxydeoxybenzoin EC(50) = 3.70 mu M (E(max) = 100%, n = 5). Deoxybenzoins displayed an endothelium-dependent relaxing manner on the contracted artery; the contractile responses of neither endothelium denuded nor L-NAME deactivated rings were inhibited. The structure activity relationships of deoxybenzoin on arterial relaxing effects concluded that the 2,4-dihydroxylated deoxybenzoins presented a potential vascular relaxing pharmacophore, with favoring substitution on ring B in the order of H >= p-OMe > p-OH > o-OMe > m,p-diOMe >= m-OMe.