(2E,5E)-2,5-bis(3,4,5-trimethoxybenzylidene)cyclopentanone

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: (2E,5E)-2,5-bis(3,4,5-trimethoxybenzylidene)cyclopentanone
• 英文别名: 2-((E)-3,4,5-trimethoxybenzylidene)-5-((E)-3,4,5-trimethoxybenzylidene)cyclopentan-1-one；2,5-bis((E)-3,4,5-trimethoxybenzylidene)cyclopentan-1-one；(2E,5E)-2,5-bis[(3,4,5-trimethoxyphenyl)methylidene]cyclopentan-1-one
• 化学式: C₂₅H₂₈O₇
• 分子量: 440.493
• InChiKey: JKCXONUCRFROOH-BEQMOXJMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  32
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  72.4
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  N-(2-hydroxyphenacyl)pyridinium iodide 、 (2E,5E)-2,5-bis(3,4,5-trimethoxybenzylidene)cyclopentanone 在 ammonium acetate 作用下， 反应 2.67h， 以30%的产率得到(E)-2-(7-(3,4,5-trimethoxybenzylidene)-4-(3,4,5-trimethoxyphenyl)-6,7-dihydro-5H-cyclopenta[b]pyridin-2-yl)phenol
  参考文献：
  名称：

  PEG-400 协助 Kröhnke 合成 2-(2-羟基苯基)-4-芳基吡啶，由 C5-C6 循环和取代的亚苄基形成环

  摘要：

  摘要 通过多组分 Kröhnke 型反应，开发了一种简单有效的合成 2-(2-羟基苯基)-4-芳基吡啶环的 C5-C6 环取代亚苄基的方法，在 PEG 中产率中等至良好。 -400。经典版本被认为是通过反合成使用交叉共轭二烯酮作为底物。图形概要

  DOI：

  10.1080/00397911.2019.1706182
• 作为产物：
  描述：

  3,4,5-三甲氧基苯甲醛 在 L-脯氨酸 作用下， 以 乙醇 、 二甲基亚砜 为溶剂， 反应 26.0h， 生成 (2E,5E)-2,5-bis(3,4,5-trimethoxybenzylidene)cyclopentanone
  参考文献：
  名称：

  哌隆明类似物的设计和绿色合成及其对脑缺血-再灌注损伤的抗氧化活性。

  摘要：

  补充外源抗氧化剂以清除过多的活性氧（ROS）是中风脑缺血再灌注损伤（CIRI）的有效治疗方法。天然生物碱Piperlongumine（PL）具有作为神经保护剂的巨大潜力，但也具有明显的毒性。而且，其神经保护作用仍有待改善。在这项研究中，我们通过筛选具有抗氧化作用的低毒双烯酮骨架和3,4,5-三甲氧基苯基基团，设计了一系列新颖的PL类似物，这可能会提高PL的抗氧化活性。通过新型绿色合成方法合成了中间体，获得了34种化合物。没有明显细胞毒性的化合物具有显着的抗氧化作用，特别是与双烯酮骨架和PL相比。通过减少双烯酮骨架中迈克尔受体的碳-碳双键，活性化合物的细胞保护作用显着降低。更重要的是，进一步的研究表明具有最佳活性的A9可以为细胞提供抗氧化应激的保护，并减轻体内的脑损伤。总体而言，这项研究为治疗CIRI提供了有希望的候选药物，并指导了在氧化应激介导的疾病中药物研究的进一步发展。

  DOI：

  10.1021/acschemneuro.9b00402

文献信息

• Synthesis and Anti-bacterial Properties of Mono-carbonyl Analogues of Curcumin
  作者：Guang Liang、Shulin Yang、Lijuan Jiang、Yu Zhao、Lili Shao、Jian Xiao、Faqing Ye、Yueru Li、Xiaokun Li

  DOI：10.1248/cpb.56.162

  日期：——

  The synthesis of three series of curcumin analogues with mono-carbonyl is described. Their in vitro anti-bacterial activities against seven Gram-positive and Gram-negative bacteria were tested and the effect of substituents on the aryl ring and the space structure of the linking strain were discussed. It was observed that part of the derivatives displayed significant activity when compared with curcumin and most of them exhibited activity against the ampicillin-resisted Enterobacter cloacae. Compounds A12, B09, B13, B14 and C09 show remarkable antibacterial activity in vitro. The result showed that heterocycle or long-chain substituents may enhance the activity of curcumin analogues.

  本文描述了三种单羰基姜黄素类似物的合成。对七种革兰氏阳性和革兰氏阴性细菌进行了体外抗菌活性测试，并讨论了取代基对芳环和连接张力的空间结构的影响。观察到，与姜黄素相比，部分衍生物显示出显著的活性，并且大多数衍生物对氨苄西林抵抗的阴沟肠杆菌表现出活性。化合物A12、B09、B13、B14和C09显示出显著的体外抗菌活性。结果显示，杂环或长链取代基可能增强姜黄素类似物的活性。
• Curcumin-like diarylpentanoid analogues as melanogenesis inhibitors
  作者：Takahiro Hosoya、Asami Nakata、Fumie Yamasaki、Faridah Abas、Khozirah Shaari、Nordin Hj Lajis、Hiroshi Morita

  DOI：10.1007/s11418-011-0568-0

  日期：2012.1

  Anti-melanogenesis screening of 47 synthesized curcumin-like diarylpentanoid analogues was performed to show that some had a potent inhibitory effect on the melanogenesis in B16 melanoma cells. Their actions were considered to be mostly due to tyrosinase inhibition, tyrosinase expression inhibition, and melanin pigment degradation. The structure–activity relationships of those curcumin-like diarylpentanoid analogues which inhibited the melanogenesis and tyrosinase activity were also discussed. Of those compounds assayed, (2E,6E)-2,6-bis(2,5-dimethoxybenzylidene)cyclohexanone showed the most potent anti-melanogenesis effect, the mechanism of which is considered to be the degradation of the melanin pigment in B16 melanoma cells, affecting neither the tyrosinase activity nor tyrosinase expression.

  对47种合成的姜黄素样二芳基戊烷类类似物进行了抗黑色素生成筛选，结果显示其中一些对B16黑色素瘤细胞的黑色素生成具有强抑制作用。这些作用主要被认为是通过抑制酪氨酸酶活性、抑制酪氨酸酶表达和降解黑色素色素实现的。还讨论了那些抑制黑色素生成和酪氨酸酶活性的姜黄素样二芳基戊烷类类似物的结构-活性关系。在测试的化合物中，（2E,6E）-2,6-双（2,5-二甲氧基苄叉）环己酮显示了最强的抗黑色素生成效果，其机制被认为是在B16黑色素瘤细胞中降解黑色素色素，既不影响酪氨酸酶活性也不影响酪氨酸酶表达。
• BP-M345 as a Basis for the Discovery of New Diarylpentanoids with Promising Antimitotic Activity
  作者：Joana Moreira、Patrícia M. A. Silva、Eliseba Castro、Lucília Saraiva、Madalena Pinto、Hassan Bousbaa、Honorina Cidade

  DOI：10.3390/ijms25031691

  日期：——

  Recently, the diarylpentanoid BP-M345 (5) has been identified as a potent in vitro growth inhibitor of cancer cells, with a GI50 value between 0.17 and 0.45 µM, showing low toxicity in non-tumor cells. BP-M345 (5) promotes mitotic arrest by interfering with mitotic spindle assembly, leading to apoptotic cell death. Following on from our previous work, we designed and synthesized a library of BP-M345 (5) analogs and evaluated the cell growth inhibitory activity of three human cancer cell lines within this library in order to perform structure–activity relationship (SAR) studies and to obtain compounds with improved antimitotic effects. Four compounds (7, 9, 13, and 16) were active, and the growth inhibition effects of compounds 7, 13, and 16 were associated with a pronounced arrest in mitosis. These compounds exhibited a similar or even higher mitotic index than BP-M345 (5), with compound 13 displaying the highest antimitotic activity, associated with the interference with mitotic spindle dynamics, inducing spindle collapse and, consequently, prolonged mitotic arrest, culminating in massive cancer cell death by apoptosis.

  最近，人们发现二芳基戊烷类化合物 BP-M345 (5) 是一种有效的体外癌细胞生长抑制剂，其 GI50 值介于 0.17 至 0.45 µM 之间，对非肿瘤细胞的毒性较低。BP-M345 (5) 通过干扰有丝分裂纺锤体的组装，促进有丝分裂停滞，导致细胞凋亡。在之前工作的基础上，我们设计并合成了一个 BP-M345 (5) 类似物文库，并评估了该文库中三种人类癌细胞株的细胞生长抑制活性，以便进行结构-活性关系（SAR）研究，并获得具有更好抗沉降作用的化合物。有四个化合物（7、9、13 和 16）具有活性，其中化合物 7、13 和 16 的生长抑制作用与明显的有丝分裂停止有关。这些化合物的有丝分裂指数与 BP-M345 (5)相似，甚至更高，其中化合物 13 的抗有丝分裂活性最高，它干扰了有丝分裂纺锤体的动力学，导致纺锤体崩溃，从而延长了有丝分裂停滞时间，最终导致大量癌细胞凋亡。
• Synthesis and anti-inflammatory activities of mono-carbonyl analogues of curcumin
  作者：Guang Liang、Xiaokun Li、Li Chen、Shulin Yang、Xudong Wu、Elaine Studer、Emily Gurley、Phillip B. Hylemon、Faqing Ye、Yueru Li、Huiping Zhou

  DOI：10.1016/j.bmcl.2007.12.068

  日期：2008.2

  Curcumin has been extensively studied for its anti-inflammatory activities. However, its potential beneficial effects on various disease preventions and treatments are limited by its unstable structure. The beta-diketone moiety renders curcumin to be rapidly metabolized by aldo -keto reductase in liver. In the present study, a series of curcumin analogues with more stable chemical structures were synthesized and several compounds showed an enhanced ability to inhibit lipopolysaccharide ( LPS)-induced TNF-alpha and IL-6 synthesis in macrophages. (C) 2007 Elsevier Ltd. All rights reserved.
• Synthesis and evaluation of curcumin-related compounds for anticancer activity
  作者：Xingchuan Wei、Zhi-Yun Du、Xi Zheng、Xiao-Xing Cui、Allan H. Conney、Kun Zhang

  DOI：10.1016/j.ejmech.2012.04.005

  日期：2012.7

  Sixty-one curcumin-related compounds were synthesized and evaluated for their anticancer activity toward cultured prostate cancer PC-3 cells, pancreas cancer Panc-1 cells and colon cancer HT-29 cells. Inhibitory effects of these compounds on the growth of PC-3. Panc-1 and HT-29 cells were determined by the MTT assay. Compounds E10, F10, FN1 and FN2 exhibited exceptionally potent inhibitory effects on the growth of cultured PC-3, Panc-1 and HT-29 cells. The IC50 for these compounds was lower than 1 mu M in all three cell lines. E10 was 72-, 46- and 117-fold more active than curcumin for inhibiting the growth of PC-3, Panc-1 and HT-29 cells, respectively. F10 was 69-, 34- and 72-fold more active than curcumin for inhibiting the growth of PC-3, Panc-1 and HT-29 cells, respectively. FN1 and FN2 had about the same inhibitory effect as E10 and F10 toward Panc-1 cells but were less active than E10 and F10 toward PC-3 and HT-29 cells. The active compounds were potent stimulators of apoptosis. The present study indicates that E10, F10, FN1 and FN2 may have useful anticancer activity. (C) 2012 Elsevier Masson SAS. All rights reserved.