trans-2,3-bis[(3-hydroxyphenyl)methyl]-γ-butyrolactone | 78473-71-9

• 物质功能分类: 化学试剂 - 有机试剂 - 酯类
• 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: trans-2,3-bis[(3-hydroxyphenyl)methyl]-γ-butyrolactone
• 英文别名: trans-dihydro-3,4-bis[(3-hydroxyphenyl)methyl]-2(3H)-furanone；trans-2,3-Bis(3-hydroxybenzyl)-γ-butyrolactone；trans-3,4-bis(3-hydroxybenzyl)-γ-butyrolactone；(+/-)-enterolactone；enterolactone；(3S,4S)-3,4-bis[(3-hydroxyphenyl)methyl]oxolan-2-one
• CAS: 78473-71-9
• 化学式: C₁₈H₁₈O₄
• 分子量: 298.339
• InChiKey: HVDGDHBAMCBBLR-PBHICJAKSA-N

物化性质

• 熔点：
  141-143°
• 沸点：
  561.4±25.0 °C(Predicted)
• 密度：
  1.298±0.06 g/cm3 (20 ºC 760 Torr)
• 溶解度：
  可溶于DMSO（少许）、甲醇（少许）
• 物理描述：
  Solid

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  22
• 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：
  66.8
• 氢给体数：
  2
• 氢受体数：
  4

安全信息

• 危险品标志：
  Xi
• 安全说明：
  S26,S36
• 危险类别码：
  R36/37/38
• WGK Germany：
  3

反应信息

• 作为反应物：
  描述：

  trans-2,3-bis[(3-hydroxyphenyl)methyl]-γ-butyrolactone 在 lithium aluminium deuteride 作用下， 以 四氢呋喃 为溶剂， 以94%的产率得到<1,1-(2)H2>-(+/-)-2,3-bis-(3-hydroxybenzyl)butane-1,4-diol
  参考文献：
  名称：

  Kirk, N. David; McLaughlin, Leo M.; Lawson, Alexander M., Journal of the Chemical Society. Perkin transactions I, 1985, p. 35 - 38

  摘要：

  DOI：
• 作为产物：
  描述：

  4-羟基-3-(3-甲氧基苄基)丁腈 在 硫酸 、 lithium diethylamide 、 三溴化硼 作用下， 以 二氯甲烷 、 水 、 溶剂黄146 为溶剂， 反应 0.5h， 生成 trans-2,3-bis[(3-hydroxyphenyl)methyl]-γ-butyrolactone
  参考文献：
  名称：

  Synthesis of compound X, a non-steroidal constituent of female urine, and congeners

  摘要：

  DOI：

  10.1016/s0040-4039(00)71128-2

文献信息

• Accurate Prediction of Glucuronidation of Structurally Diverse Phenolics by Human UGT1A9 Using Combined Experimental and In Silico Approaches
  作者：Baojian Wu、Xiaoqiang Wang、Shuxing Zhang、Ming Hu

  DOI：10.1007/s11095-012-0666-z

  日期：2012.6

  Catalytic selectivity of human UGT1A9, an important membrane-bound enzyme catalyzing glucuronidation of xenobiotics, was determined experimentally using 145 phenolics and analyzed by 3D-QSAR methods. Catalytic efficiency of UGT1A9 was determined by kinetic profiling. Quantitative structure activity relationships were analyzed using CoMFA and CoMSIA techniques. Molecular alignment of substrate structures was made by superimposing the glucuronidation site and its adjacent aromatic ring to achieve maximal steric overlap. For a substrate with multiple active glucuronidation sites, each site was considered a separate substrate. 3D-QSAR analyses produced statistically reliable models with good predictive power (CoMFA: q2 = 0.548, r2 = 0.949, r pred 2  = 0.775; CoMSIA: q2 = 0.579, r2 = 0.876, r pred 2  = 0.700). Contour coefficient maps were applied to elucidate structural features among substrates that are responsible for selectivity differences. Contour coefficient maps were overlaid in the catalytic pocket of a homology model of UGT1A9, enabling identification of the UGT1A9 catalytic pocket with a high degree of confidence. CoMFA/CoMSIA models can predict substrate selectivity and in vitro clearance of UGT1A9. Our findings also provide a possible molecular basis for understanding UGT1A9 functions and substrate selectivity.

  通过实验使用145种酚类化合物，并通过3D-QSAR方法分析，确定了人UGT1A9的催化选择性。UGT1A9是一种重要的膜结合酶，催化外源性物质的葡糖醛酸化反应。通过动力学分析确定了UGT1A9的催化效率。使用CoMFA和CoMSIA技术分析了定量结构活性关系。通过将葡糖醛酸化位点及其相邻的芳香环重叠，实现了底物结构的最大立体重叠。对于具有多个活性葡糖醛酸化位点的底物，每个位点被视为单独的底物。3D-QSAR分析产生了统计上可靠的模型，具有良好的预测能力（CoMFA：q2=0.548，r2=0.949，r pred 2=0.775；CoMSIA：q2=0.579，r2=0.876，r pred 2=0.700）。通过轮廓系数图阐明了底物中负责选择性差异的结构特征。将轮廓系数图叠加在UGT1A9的同源模型的催化口袋中，能够高度自信地识别UGT1A9的催化口袋。CoMFA/CoMSIA模型可以预测底物的选择性和UGT1A9的体外清除率。我们的发现还提供了理解UGT1A9功能和底物选择性的可能分子基础。
• Oxidative Metabolism of the Mammalian Lignans Enterolactone and Enterodiol by Rat, Pig, and Human Liver Microsomes
  作者：Eric Jacobs、Manfred Metzler

  DOI：10.1021/jf9809176

  日期：1999.3.1

  microsomes from aroclor-treated male Wistar rats biotransform enterolactone to 12 metabolites, six of which carry an additional hydroxy group at the aromatic and six at the aliphatic moiety according to HPLC/MS and GC/MS analysis. The aromatic hydroxylation products were identified with the help of synthesized reference compounds as enterolactone monohydroxylated in the para position and in both ortho positions

  根据HPLC / MS和GC / MS分析，用acrolor处理的雄性Wistar大鼠的肝微粒体将肠内酯生物转化为12种代谢物，其中6种在芳族上带有一个额外的羟基，在脂族部分上带有6个羟基。借助于合成的参考化合物，芳族羟基化产物鉴定为肠内酯在任一芳族环的原始酚羟基的对位和两个邻位均被单羟基化。描述了参考化合物的合成及其光谱表征。肠糖被肝微粒体从经aroclor处理的雄性大鼠代谢为三种芳香族和四种脂肪族单羟基化代谢产物。芳族羟基化发生在原始酚羟基的对位和两个邻位。
• Chemical synthesis of the first lignans to be found in humans and animals
  作者：George Cooley、R.Duncan Farrant、David N. Kirk、Steven Wynn

  DOI：10.1016/0040-4039(81)80094-9

  日期：1981.1

  Trans-2,3-bis-(3′-hydroxybenzyl)-butyrolactone (1) and 2,3-bis-(3′-hydroxybenzyl)-butane-1,4-diol (2), recently identified in urine, have been synthesised in racemic form.

  最近在尿液中发现的反式-2,3-双-（3'-羟基苄基）-丁内酯（1）和2,3-双-（3'-羟基苄基）-丁烷-1,4-二醇（2）具有以外消旋形式合成。
• Dimetalated tertiary succinamides. Synthesis of several classes of lignans including the mammalian urinary lignas enterolactone and enterodiol
  作者：K.K. Mahalanabis、M. Mumtaz、V. Snieckus

  DOI：10.1016/s0040-4039(00)88673-6

  日期：1982.1

  Reaction of dimetalated succinamides with benzyl halides and aromatic aldehydes provides short routes to diverse lignan natural products , , and , including the human urinary metabolites () and ().

  用苄基卤化物和芳族醛dimetalated琥珀酰胺的反应提供短的路由不同的木酚素的天然产物，和，其中包括人尿代谢物（）和（）。
• Transformation of Arctiin to Estrogenic and Antiestrogenic Substances by Human Intestinal Bacteria.
  作者：Li-Hua Xie、Eun-Mi Ahn、Teruaki Akao、Atef Abdel-Monem Abdel-Hafez、Norio Nakamura、Masao Hattori

  DOI：10.1248/cpb.51.378

  日期：——

  After anaerobic incubation of arctiin (1) from the seeds of Arctium lappa with a human fecal suspension, six metabolites were formed, and their structures were identified as (−)-arctigenin (2), (2R,3R)-2-(3′,4′-dihydroxybenzyl)-3-(3″,4″-dimethoxybenzyl)butyrolactone (3), (2R,3R)-2-(3′-hydroxybenzyl)-3-(3″,4″-dimethoxybenzyl)butyrolactone (4), (2R,3R)-2-(3′-hydroxybenzyl)-3-(3″-hydroxy-4″-methoxybenzyl)butyrolactone (5), (2R,3R)-2-(3′-hydroxybenzyl)-3-(3″,4″-dihydroxybenzyl)butyrolactone (6), and (−)-enterolactone (7) by various spectroscopic means including two dimensional (2D)-NMR, mass spectrometry, and circular dichroism. A possible metabolic pathway was proposed on the basis of their structures and the time course of the transformation. Enterolactones obtained from the biotransformation of arctiin and secoisolariciresinol diglucoside (SDG, from the seeds of Linum usitatissium) by human intestinal bacteria were proved to be enantiomers, with the (−)-(2R,3R) and (+)-(2S,3S) configurations, respectively. Compound 6 showed the most potent proliferative effect on the growth of MCF-7 human breast cancer cells in culture among 1 and six metabolites, while it showed inhibitory activity on estradiol-mediated proliferation of MCF-7 cells at a concentration of 10 μM. These results indicate that the transformation of 1 by intestinal flora might be essential for the manifestation of the estrogenic and antiestrogenic activity of 1.

  将从蒡子中提取的 arctiin（1）与人类粪便悬浮液进行厌氧培养后，产生了六种代谢物、它们的结构被鉴定为(-)-旱芹甙元（2）、(2R,3R)-2-(3′,4′-二羟基苄基)-3-(3″,4″-二甲氧基苄基)丁内酯（3）、(2R,3R)-2-(3′-羟基苄基)-3-(3″、4″-二甲氧基苄基）丁内酯 (4)，(2R,3R)-2-（3′-羟基苄基）-3-（3″-羟基-4″-甲氧基苄基）丁内酯 (5)，(2R,3R)-2-（3′-羟基苄基）-3-（3″、4″-二羟基苄基）丁内酯 (6) 和 (-)- 肠内酯 (7)。根据它们的结构和转化的时间过程，提出了一种可能的代谢途径。经人体肠道细菌对 arctiin 和 secoisolariciresinol diglucoside（SDG，来自 Linum usitatissium 的种子）进行生物转化后得到的肠内酯被证明是对映体，分别具有 (-)-(2R,3R) 和 (+)-(2S,3S) 构型。在 1 和 6 个代谢物中，化合物 6 对 MCF-7 人乳腺癌细胞的增殖作用最强，而在 10 μ<小>M浓度下，它对雌二醇介导的 MCF-7 细胞增殖具有抑制活性。这些结果表明，肠道菌群对 1 的转化可能是 1 显示雌激素和抗雌激素活性的关键。