(-)-(2R,3R)-2-(3',4'-dihydroxybenzyl)-3-(3'',4''-dihydroxybenzyl)butyrolactone | 119098-95-2

• 分子结构分类: 有机化合物 - 木脂素、新木脂素和相关化合物 - 呋喃类木脂素
• 英文名称: (-)-(2R,3R)-2-(3',4'-dihydroxybenzyl)-3-(3'',4''-dihydroxybenzyl)butyrolactone
• 英文别名: 3-(3,4-dihydroxybenzyl)-4-(3,4-dihydroxybenzyl)dihydrofuran-2(3H)-one；(2R,3R)-2,3-bis(3,4-dihydroxybenzyl)butyrolactone；(-)-4',4"-dihydroxyenterolactone；(2R,3R)-(-)-dihydroxyenterolactone；3,3′-didemethylmatairesinol；4,4'-dihydroxy-enterolactone；(3R,4R)-3,4-bis(3,4-dihydroxybenzyl)dihydrofuran-2(3H)-one；(3R,4R)-3,4-bis[(3,4-dihydroxyphenyl)methyl]oxolan-2-one
• CAS: 119098-95-2
• 化学式: C₁₈H₁₈O₆
• 分子量: 330.337
• InChiKey: NXJDDTDNGCHIGR-QWHCGFSZSA-N

物化性质

• 沸点：
  655.9±50.0 °C(Predicted)
• 密度：
  1.457±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  107
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (-)-(2R,3R)-2-(3',4'-dihydroxybenzyl)-3-(3'',4''-dihydroxybenzyl)butyrolactone 在 Eggerthella sp. CAT-1 作用下， 反应 120.0h， 生成 (-)-enterolactone
  参考文献：
  名称：

  Isolation and Characterization of a Human Intestinal Bacterium <i>Eggerthella</i> sp. CAT-1 Capable of Cleaving the C-Ring of (+)-Catechin and (−)-Epicatechin, Followed by <i>p</i>-Dehydroxylation of the B-Ring

  摘要：

  我们分离出一种人类肠道细菌，能够裂解 (+)-儿茶素 (2R,3S) 和 (−)-表儿茶素 (2R,3R) 的 C 环并使 B 环脱羟基。尽管该菌株被归类为 Eggerthella (Eg.) lenta [命名为 Eg. sp。 CAT-1 (JF798636)] 通过 16S 核糖体 RNA (rRNA) 基因相似性，其底物特异性与先前分离的菌株（例如 CAT-1 (JF798636)）有很大不同。 sp。 SDG-2，参与(3R)-黄烷-3-醇衍生物的C环裂解和3,4-二羟基苯基部分（B环）的脱羟基。另一方面，例如。 sp。 CAT-1 和例如。 sp。 SDG-2 对对映体木脂素、(+)- 和 (-)-二羟基肠二醇、以及 (+)- 和 (-)-二羟基肠内酯的脱羟基表现出相同的底物特异性。

  DOI：

  10.1248/bpb.b12-00726
• 作为产物：
  描述：

  开环异落叶松树脂酚 在 Ruminococcus sp. END-1 作用下， 反应 120.0h， 生成 (-)-(2R,3R)-2-(3',4'-dihydroxybenzyl)-3-(3'',4''-dihydroxybenzyl)butyrolactone
  参考文献：
  名称：

  Further Studies on a Human Intestinal Bacterium Ruminococcus sp. END-1 for Transformation of Plant Lignans to Mammalian Lignans

  摘要：

  A human intestinal bacterium Ruminococcus (R.) sp. END-1 capable of oxidizing (-)-enterodiol to (-)-enterolactone, enantioselectively, was further investigated from the perspective of transformation of plant lignans to mammalian lignans; A cell-free extract of the bacterium transformed (-)-enterodiol to (-)-enterolactone through an intermediate, enterolactol. The bacterium showed not only oxidation but also demethylation and deglucosylation activities for plant lignans. Arctiin and secoisolariciresinol diglucoside were converted to (-)-dihydroxyenterolactone and (+)-dihydroxyenterodiol, respectively. Moreover, by coincubation with Eggerthella sp. SDG-2, the bacterium transformed arctiin and secoisolariciresinol diglucoside to (-)-enterolactone and (+)-enterodiol, respectively.

  DOI：

  10.1021/jf900902p

文献信息

• (−)-Arctigenin as a Lead Structure for Inhibitors of Human Immunodeficiency Virus Type-1 Integrase
  作者：Eckart Eich、Heinz Pertz、Macki Kaloga、Jutta Schulz、Mark R. Fesen、Abhijit Mazumder、Yves Pommier

  DOI：10.1021/jm950387u

  日期：1996.1.1

  congener with two catechol substructures (7) was found to be the most active compound in this study. 7 was also a potent inhibitor of the "disintegration" reaction which models the reversal of the strand transfer reaction. The inhibitory activity of 7 with the core enzyme fragment consisting of amino acids 50-212 suggests that the binding site of 7 resides in the catalytic domain.

  发现天然二苄基丁内酯型木质素（-）-arctigenin（2）是一种人类免疫缺陷病毒1型（HIV-1）在感染的人类细胞系统中复制的抑制剂，可抑制前病毒DNA整合到细胞DNA基因组中。在本研究中，2用纯化的HIV-1整合酶进行了测试，发现在裂解（3'-加工）和整合（链转移）测定中无活性。然而，以儿茶酚亚结构为特征的半合成3-O-去甲基化同源物9在两种测定中均表现出显着的活性。用30种天然（1-6），半合成（7-21）和合成（37-43、45、46）的木脂素进行结构-活性关系研究表明，（1）内酯部分至关重要，因为带有丁烷-1的化合物，4-二醇或四氢呋喃的亚结构以及木脂酰胺类似物缺乏活性，（2）酚羟基的数量和排列对于木质素的活性很重要。在本研究中，发现具有两个邻苯二酚亚结构的同类物（7）是活性最高的化合物。7也是“崩解”反应的有效抑制剂，其模拟了链转移反应的逆转。7对由氨基酸50-212组成的核
• Identification of lignans by liquid chromatography-electrospray ionization ion-trap mass spectrometry
  作者：Patrik C. Eklund、M. Josefin Backman、Leif Å. Kronberg、Annika I. Smeds、Rainer E. Sjöholm

  DOI：10.1002/jms.1276

  日期：——

  The fragmentation pattern of 30 compounds belonging to different classes of the lignan family was studied by liquid chromatography-electrospray ionization ion-trap mass spectrometry. On the basis of the observed fragmentation patterns, identification of different types of lignans was achieved. For example, dibenzylbutyrolactone lignans showed a characteristic fragmentation pathway by the loss of 44 Da (CO2) from the lactone moiety, whereas dibenzylbutanediols showed a loss of 48 Da by a combined loss of formaldehyde and water from the 1,4-butanediol moiety. Lignan glycosides readily lost the sugar residue to give the parent lignan as their primary product ion. In addition, several compound-specific fragmentations were observed and used for identification of individual compounds. A versatile method for analyses of lignans was developed using LC separation on a C8 column followed by fragmentation and detection of ions produced in the ion trap. Copyright © 2007 John Wiley & Sons, Ltd.

  液相色谱-电喷雾离子阱质谱法研究了属于木质素家族不同类别的 30 种化合物的碎片模式。根据观察到的碎片模式，对不同类型的木质素进行了鉴定。例如，二苄基丁内酯木质素的特征碎片途径是从内酯分子中损失 44 Da（CO2），而二苄基丁二醇的特征碎片途径是从 1,4 丁二醇分子中损失 48 Da（甲醛和水）。木质素苷很容易失去糖残基，从而得到作为主要产物离子的母体木质素。此外，还观察到了几种化合物的特异性片段，并可用于单个化合物的鉴定。 通过在 C8 色谱柱上进行液相色谱分离，然后对离子阱中产生的离子进行破碎和检测，开发出了一种分析木质素的多功能方法。Copyright © 2007 John Wiley & Sons, Ltd. All Rights Reserved.
• Pharmaceutical compositions comprising 8-substituted dibenzylbutyrolactone lignans
  申请人：Peuhu Emilia

  公开号：US09168243B2

  公开（公告）日：2015-10-27

  Therapeutic compositions comprising at least one 8-substituted-dibenzylbutyrolactone lignan, preferably a lignan is selected from the group of nortrachelogenin, diasteromeric forms of nortrachelogenin, isomeric forms of nortrachelogenin and combinations thereof as well as 8-methylmatairesinol and 8-methyldimethylmatairesinol, for use in a method of treating cancer or a similar condition wherein the growth factor signaling pathway of a mammal is deregulated. The invention also provides therapeutic pharmaceutical combinations comprising a hydroxy-dibenzylbutyrolactone lignan and at least one TRAIL receptor agonist. The hydroxy-dibenzylbutyrolactone lignans and a TRAIL receptor agonist can be used as a combined preparation for administration to a patient simultaneously, separately or spaced out over a period of time in treating cancer.

  包含至少一种8-取代二苯丁酸内酯木脂素的治疗组合物，优选的木脂素选自诺特拉赫洛根醇、诺特拉赫洛根醇的两对映异构体、诺特拉赫洛根醇的异构体以及它们的组合，还包括8-甲基马泰雷辛醇和8-甲基二甲基马泰雷辛醇，用于治疗癌症或类似疾病的方法，其中哺乳动物的生长因子信号通路发生了失调。该发明还提供了治疗性药物组合，包括羟基二苯丁酸内酯木脂素和至少一种TRAIL受体激动剂。羟基二苯丁酸内酯木脂素和TRAIL受体激动剂可以作为联合制剂同时、分开或在一段时间内分开使用，用于治疗癌症。
• ( − )-Arctigenin as a lead compound for anticancer agent
  作者：Gui-Rong Chen、Hong-Fu Li、De-Qiang Dou、Yu-Bin Xu、Hong-Shuai Jiang、Fu-Rui Li、Ting-Guo Kang

  DOI：10.1080/14786419.2013.821120

  日期：2013.12

  (-)-Arctigenin, an important active constituent of the traditional Chinese herb Fructus Arctii, was found to exhibit various bioactivities, so it can be used as a good lead compound for further structure modification in order to find a safer and more potent medicine. (-)-Arctigenin derivatives 1-5 of (-)-arctingen were obtained by modifying with ammonolysis at the lactone ring and sulphonylation at C (6) and C (6) and O-demethylation at CH3O-C (3), CH3O-C (3) and CH3O-C (4), and their anticancer bioactivities were examined.

  (-)-去甲乌药碱是传统中药牛蒡子中的重要活性成分，已被发现具有多种生物活性，因此可以用作进一步结构改造的良好先导化合物，以寻找更安全、更有效的药物。通过对(-)-去甲乌药碱进行内酯环氨解、C(6)和C(6)位的磺化，以及CH3O-C(3)、CH3O-C(3)和CH3O-C(4)位的O-脱甲基化修饰，得到了(-)-去甲乌药碱的衍生物1-5，并对其抗肿瘤生物活性进行了研究。
• Design, Semisynthesis, and Estrogenic Activity of Lignan Derivatives from Natural Dibenzylbutyrolactones
  作者：Priscila López-Rojas、Ángel Amesty、Miguel Guerra-Rodríguez、Yeray Brito-Casillas、Borja Guerra、Leandro Fernández-Pérez、Ana Estévez-Braun

  DOI：10.3390/ph15050585

  日期：——

  Based on molecular docking studies on the ERα, a series of lignan derivatives (3–16) were designed and semisynthesized from the natural dibenzylbutyrolactones bursehernin (1) and matairesinol dimethyl ether (2). To examine their estrogenic and antiestrogenic potencies, the effects of these compounds on estrogen receptor element (ERE)-driven reporter gene expression and viability in human ER+ breast cancer cells were evaluated. Lignan compounds induced ERE-driven reporter gene expression with very low potency as compared with the pure agonist E2. However, coincubation of 5 μM of lignan derivatives 1, 3, 4, 7, 8, 9, 11, 13, and 14 with increasing concentrations of E2 (from 0.01 pM to 1 nM) reduced both the potency and efficacy of pure agonists. The binding to the rhERα-LBD was validated by TR-FRET competitive binding assay and lignans bound to the rhERα with IC50 values from 0.16 μM (compound 14) to 6 μM (compound 4). Induced fit docking (IFD) and molecular dynamics (MD) simulations for compound 14 were carried out to further investigate the binding mode interactions. Finally, the in silico ADME predictions indicated that the most potent lignan derivatives exhibited good drug-likeness.

  基于对ERα的分子对接研究，一系列木脂素衍生物（3-16）从天然的二苯基丁酸内酯bursehernin（1）和matairesinol二甲醚（2）中设计并半合成。为了检查它们的雌激素和抗雌激素效力，评估了这些化合物对ER+人类乳腺癌细胞中ER元件驱动的报告基因表达和细胞生存率的影响。与纯激动剂E2相比，木脂素化合物诱导的ER元件驱动的报告基因表达的效力非常低。然而，在5μM的木脂素衍生物1、3、4、7、8、9、11、13和14的共孵育下，随着E2浓度（从0.01 pM到1 nM）的增加，纯激动剂的效力和效能均降低。通过TR-FRET竞争结合测定验证了与rhERα-LBD的结合，并且木脂素与rhERα的IC50值从0.16μM（化合物14）到6μM（化合物4）不等。对于化合物14，进行了诱导适应性对接（IFD）和分子动力学（MD）模拟以进一步研究结合模式和相互作用。最后，计算机辅助预测ADME表明，最有效的木脂素衍生物表现出良好的药物相似性。