3'-O-去甲基牛蒡子苷元 | 147022-95-5

• 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
• 中文名称: 3'-O-去甲基牛蒡子苷元
• 英文名称: 3'-demethylarctigenin
• 英文别名: (3R,4R)-3-(3,4-dihydroxybenzyl)-4-(3,4-dimethoxybenzyl)dihydrofuran-2-one；3-(3,4-dihydroxybenzyl)-4-(3,4-dimethoxybenzyl)dihydrofuran-2(3H)-one；3′‐desmethylarctigenin；(8R,8'R)-3,4-dihydroxy-3',4'-dimethoxylignano-9,9'-lactone；PP-6 (Piper philippinum)；3'-desmethylarctigenin；3'-O-Demethylarctigenin；(3R,4R)-3-[(3,4-dihydroxyphenyl)methyl]-4-[(3,4-dimethoxyphenyl)methyl]oxolan-2-one
• CAS: 147022-95-5
• 化学式: C₂₀H₂₂O₆
• 分子量: 358.391
• InChiKey: FTDOXLKYCKOSHA-LSDHHAIUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  85.2
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3'-O-去甲基牛蒡子苷元 在 氢气 、 palladium(II) hydroxide 、 potassium carbonate 、 三苯基膦 、 potassium iodide 作用下， 以 甲醇 、 二氯甲烷 、 丙酮 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 21.0h， 生成 (3R,4R)-4-[(3,4-dimethoxyphenyl)methyl]-3-[[4-hydroxy-3-(2-hydroxyethoxy)phenyl]methyl]oxolan-2-one
  参考文献：
  名称：

  Synthesis and antitumor evaluation of arctigenin derivatives based on antiausterity strategy

  摘要：

  A series of new (-)-arctigenin derivatives with variably modified O-alkyl groups were synthesized and their preferential cytotoxicity was evaluated against human pancreatic cancer cell line PANC-1 under nutrient-deprived conditions. The results showed that monoethoxy derivative 4i (PC50, 0.49 mu M), diethoxy derivative 4h (PC50, 0.66 mu M), and triethoxy derivative 4m (PC50, 0.78. mu M) showed the preferential cytotoxicities under nutrient-deprived conditions, which were identical to or more potent than (-)-arctigenin (1) (PC50, 0.80 mu M). Among them, we selected the triethoxy derivative 4m and examined its in vivo antitumor activity using a mouse xenograft model. Triethoxy derivative 4m exhibited also in vivo antitumor activity with the potency identical to or slightly more than (-)-arctigenin (1). These results would suggest that a modification of (-)-arctigenin structure could lead to a new drug based on the antiausterity strategy. (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.11.031
• 作为产物：
  描述：

  牛蒡子苷元 在 吡啶 、 aluminum (III) chloride 作用下， 反应 12.0h， 以57%的产率得到3'-O-去甲基牛蒡子苷元
  参考文献：
  名称：

  ( − )-Arctigenin as a lead compound for anticancer agent

  摘要：

  (-)-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。

  DOI：

  10.1080/14786419.2013.821120

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
• ( − )-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。
• Discovery of stereospecific cytotoxicity of (8R,8′R)-trans-arctigenin against insect cells and structure-activity relationship on aromatic ring
  作者：Satoshi Yamauchi、Asuka Nishimoto、Hisashi Nishiwaki、Kosuke Nishi、Takuya Sugahara

  DOI：10.1016/j.bmcl.2020.127191

  日期：2020.7

  One of the arctigenin stereoisomers, (8R,8'R)-trans-form 1, showed stereospecific cytotoxicity against insect cells, Sf9 and NIAS-AeAl-2 cells. By the comparison with other stereoisomers, the most importance of the 8'R stereochemistry for the higher activities was clarified. On the other hand, the wider range of activity level among stereoisomers against cancer cells, HL-60, was not observed. The structure-activity relationship research using derivatives bearing (8R,8'R)-trans-form was performed to show the same level of activities of 3-iodo, 4-iodo, and 3,4-methylenedioxy derivatives 28, 29, and 36 as (8R,8'R)-trans-arctigenin 1. In the examination of thiono derivatives, 4-iodo thiono and 3,4-methylenedioxy thiono derivatives 66, 67 showed similar level of activities to that of (8R,8'R)-trans-arctigenin 1. The expression of ribosomal 28S rRNA gene of Sf9 cells was increased by (8R,8'R)-trans-arctigenin 1, whereas a degradation of DNA was not observed.
• Synthesis and antitumor evaluation of arctigenin derivatives based on antiausterity strategy
  作者：Naoki Kudou、Akira Taniguchi、Kenji Sugimoto、Yuji Matsuya、Masashi Kawasaki、Naoki Toyooka、Chika Miyoshi、Suresh Awale、Dya Fita Dibwe、Hiroyasu Esumi、Shigetoshi Kadota、Yasuhiro Tezuka

  DOI：10.1016/j.ejmech.2012.11.031

  日期：2013.2

  A series of new (-)-arctigenin derivatives with variably modified O-alkyl groups were synthesized and their preferential cytotoxicity was evaluated against human pancreatic cancer cell line PANC-1 under nutrient-deprived conditions. The results showed that monoethoxy derivative 4i (PC50, 0.49 mu M), diethoxy derivative 4h (PC50, 0.66 mu M), and triethoxy derivative 4m (PC50, 0.78. mu M) showed the preferential cytotoxicities under nutrient-deprived conditions, which were identical to or more potent than (-)-arctigenin (1) (PC50, 0.80 mu M). Among them, we selected the triethoxy derivative 4m and examined its in vivo antitumor activity using a mouse xenograft model. Triethoxy derivative 4m exhibited also in vivo antitumor activity with the potency identical to or slightly more than (-)-arctigenin (1). These results would suggest that a modification of (-)-arctigenin structure could lead to a new drug based on the antiausterity strategy. (C) 2012 Elsevier Masson SAS. All rights reserved.