(2R,3R)-2-[(2S,3S)-3-(3,4-dimethoxyphenyl)-2-(methoxymethyl)-2,3-dihydro-1,4-benzodioxin-6-yl]-3-hydroxy-5,7-dimethoxy-2,3-dihydrochromen-4-one | 1420659-29-5

• 分子结构分类: 有机化合物 - 木脂素、新木脂素和相关化合物 - 黄酮木脂素
• 英文名称: (2R,3R)-2-[(2S,3S)-3-(3,4-dimethoxyphenyl)-2-(methoxymethyl)-2,3-dihydro-1,4-benzodioxin-6-yl]-3-hydroxy-5,7-dimethoxy-2,3-dihydrochromen-4-one
• CAS: 1420659-29-5
• 化学式: C₂₉H₃₀O₁₀
• 分子量: 538.551
• InChiKey: LBOJKFQTJUQFEL-HSNHEXMOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  39
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.34
• 拓扑面积：
  111
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  硫酸二甲酯 、 silybin B 在 potassium carbonate 作用下， 以 丙酮 为溶剂， 反应 0.5h， 以16.7%的产率得到(2R,3R)-2-[(2S,3S)-3-(3,4-dimethoxyphenyl)-2-(hydroxymethyl)-2,3-dihydro-1,4-benzodioxin-6-yl]-3-hydroxy-5,7-dimethoxy-2,3-dihydrochromen-4-one
  参考文献：
  名称：

  Enhanced bioactivity of silybin B methylation products

  摘要：

  Flavonolignans from milk thistle (Silybum marianum) have been investigated for their cellular modulatory properties, including cancer chemoprevention and hepatoprotection, as an extract (silymarin), as partially purified mixtures (silibinin and isosilibinin), and as pure compounds (a series of seven isomers). One challenge with the use of these compounds in vivo is their relatively short half-life due to conjugation, particularly glucuronidation. In an attempt to generate analogues with improved in vivo properties, particularly reduced metabolic liability, a semi-synthetic series was prepared in which the hydroxy groups of silybin B were alkylated. A total of five methylated analogues of silybin B were synthesized using standard alkylation conditions (dimethyl sulfate and potassium carbonate in acetone), purified using preparative HPLC, and elucidated via spectroscopy and spectrometry. Of the five, one was monomethylated (3), one was dimethylated (4), two were trimethylated (2 and 6), and one was tetramethylated (5). The relative potency of all compounds was determined in a 72 h growth-inhibition assay against a panel of three prostate cancer cell lines (DU-145, PC-3, and LNCaP) and a human hepatoma cell line (Huh7.5.1) and compared to natural silybin B. Compounds also were evaluated for inhibition of both cytochrome P450 2C9 (CYP2C9) activity in human liver microsomes and hepatitis C virus infection in Huh7.5.1 cells. The monomethyl and dimethyl analogues were shown to have enhanced activity in terms of cytotoxicity, CYP2C9 inhibitory potency, and antiviral activity (up to 6-fold increased potency) compared to the parent compound, silybin B. In total, these data suggested that methylation of flavonolignans can increase bioactivity. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.11.035

文献信息

• Enhanced bioactivity of silybin B methylation products
  作者：Arlene A. Sy-Cordero、Tyler N. Graf、Scott P. Runyon、Mansukh C. Wani、David J. Kroll、Rajesh Agarwal、Scott J. Brantley、Mary F. Paine、Stephen J. Polyak、Nicholas H. Oberlies

  DOI：10.1016/j.bmc.2012.11.035

  日期：2013.2

  Flavonolignans from milk thistle (Silybum marianum) have been investigated for their cellular modulatory properties, including cancer chemoprevention and hepatoprotection, as an extract (silymarin), as partially purified mixtures (silibinin and isosilibinin), and as pure compounds (a series of seven isomers). One challenge with the use of these compounds in vivo is their relatively short half-life due to conjugation, particularly glucuronidation. In an attempt to generate analogues with improved in vivo properties, particularly reduced metabolic liability, a semi-synthetic series was prepared in which the hydroxy groups of silybin B were alkylated. A total of five methylated analogues of silybin B were synthesized using standard alkylation conditions (dimethyl sulfate and potassium carbonate in acetone), purified using preparative HPLC, and elucidated via spectroscopy and spectrometry. Of the five, one was monomethylated (3), one was dimethylated (4), two were trimethylated (2 and 6), and one was tetramethylated (5). The relative potency of all compounds was determined in a 72 h growth-inhibition assay against a panel of three prostate cancer cell lines (DU-145, PC-3, and LNCaP) and a human hepatoma cell line (Huh7.5.1) and compared to natural silybin B. Compounds also were evaluated for inhibition of both cytochrome P450 2C9 (CYP2C9) activity in human liver microsomes and hepatitis C virus infection in Huh7.5.1 cells. The monomethyl and dimethyl analogues were shown to have enhanced activity in terms of cytotoxicity, CYP2C9 inhibitory potency, and antiviral activity (up to 6-fold increased potency) compared to the parent compound, silybin B. In total, these data suggested that methylation of flavonolignans can increase bioactivity. (C) 2012 Elsevier Ltd. All rights reserved.