7-O-benzylsilybin | 871249-28-4

• 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: 7-O-benzylsilybin
• 英文别名: (2R,3R)-3,5-dihydroxy-2-[3-(4-hydroxy-3-methoxyphenyl)-2-(hydroxymethyl)-2,3-dihydro-1,4-benzodioxin-6-yl]-7-phenylmethoxy-2,3-dihydrochromen-4-one
• CAS: 871249-28-4
• 化学式: C₃₂H₂₈O₁₀
• 分子量: 572.568
• InChiKey: VDACAOPMTDRTEZ-RBIPZIAJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  42
• 可旋转键数：
  7
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  144
• 氢给体数：
  4
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  7-O-benzylsilybin 在 palladium on activated charcoal 、 甲酸铵 、 potassium carbonate 作用下， 以 甲醇 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 生成 5-O-pentyl-2,3-dehydrosilybin
  参考文献：
  名称：

  5- or/and 20-O-alkyl-2,3-dehydrosilybins: Synthesis and biological profiles on prostate cancer cell models

  摘要：

  To investigate the effects of alkylation at 5-OH and 20-OH of 2,3-dehydrosilybin on prostate cancer cell proliferation, the synthetic approaches to 5- or/and 20-O-alkyl-2,3-dehydrosilybins, through a multi-step sequence from commercially available silybin, have been successfully developed. The first three reactions in the syntheses were completed through a one-pot procedure by managing anaerobic and aerobic conditions. With these synthetic methods in hand, twenty-one 2,3-dehydrosilybins, including seven 20-0-alkyl, seven 5,20-O-dialkyl, and seven 5-O-alkyl-2,3-dehydrosilybins, have been achieved for the evaluation of their biological profiles. Our WST-1 cell proliferation assay data indicate that nineteen out of the twenty-one 2,3-dehydrosilybins possess significantly improved antiproliferative potency as compared with silybin toward both androgen-sensitive (LNCaP) and androgen-insensitive prostate cancer cell lines (PC-3 and DU145). 5-O-Alkyl-2,3-dehydrosilybins were identified as the optimal subgroup that can consistently inhibit cell proliferation in three prostate cancer cell models with all IC50 values lower than 8 OA. Our flow cytometry-based assays also demonstrate that 5-O-heptyl-2,3-dehydrosilybin effectively arrests the cell cycle in the Go/GI phase and activates PC-3 cell apoptosis. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2017.07.035
• 作为产物：
  描述：

  水飞蓟素A,B 、 溴甲苯 在 potassium carbonate 作用下， 以 丙酮 为溶剂， 以81%的产率得到7-O-benzylsilybin
  参考文献：
  名称：

  3 - O-烷基-2,3-脱氢水飞蓟宾素：两种合成方法及对前列腺癌细胞的体外作用

  摘要：

  八个3- O-烷基-2，3-脱氢水飞蓟宾素已经通过两种合成方法由市售的水飞蓟宾素合成。一锅反应，首先将水飞蓟宾的好氧氧化，然后在随后的2,3-脱氢水飞蓟宾中将酚羟基直接烷基化，从而以11–16％的收率提供所需的衍生物。使用苄基醚保护水飞蓟宾中的7-OH的三步过程以30-46％的总收率生成所需的衍生物。已经使用WST-1细胞增殖测定法评估了2，3-脱氢水飞蓟宾衍生物对雄激素敏感和雄激素不敏感的前列腺癌细胞的抗增殖活性。所有衍生物均具有比水飞蓟宾更大的抗增殖能力，其中2,3-脱氢水飞蓟宾均具有3至5个碳原子的3 -OH直链烷基（IC针对PC-3和LNCaP细胞的50个值，范围为1.71–3.06μM，是最佳衍生物。使用三至五个碳原子的烷基可以达到最佳效价。我们的发现表明3 - O-丙基-2,3-脱氢水飞蓟宾可通过将细胞周期阻滞在G 0 / G 1期来有效抑制PC-3前列腺癌细胞的生长，而不是通

  DOI：

  10.1016/j.bmcl.2016.05.069

文献信息

• Effects of 2,3-Dehydrosilybin and Its Galloyl Ester and Methyl Ether Derivatives on Human Umbilical Vein Endothelial Cells
  作者：Daniel Karas、Radek Gažák、Kateřina Valentová、Christopher S. Chambers、Veronika Pivodová、David Biedermann、Alena Křenková、Ivana Oborná、Marek Kuzma、Josef Cvačka、Jitka Ulrichová、Vladimír Křen

  DOI：10.1021/acs.jnatprod.5b00905

  日期：2016.4.22

  The effects in vitro of 2,3-dehydrosilybin and several galloyl esters and methyl ethers on the viability, proliferation, and migration of human umbilical vein endothelial cells (HUVECs) were evaluated. The monogalloyl esters were synthesized by a chemoselective esterification method or by Steglich esterification of suitably protected 2,3-dehydrosilybin (1) with protected gallic acid. 2,3-Dehydrosilybin

  评估了2,3-脱氢水飞蓟宾和几种没食子酸酯和甲基醚对人脐静脉内皮细胞（HUVEC）的活力，增殖和迁移的影响。通过化学选择性酯化方法或通过适当保护的2，3-脱氢水飞蓟宾（1）与受保护的没食子酸的斯特列奇酯化反应合成单没食子酸酯。2,3- Dehydrosilybin（1）中显示的更有效的细胞毒性，抗增殖，抗迁移和活性（IC 50 12.0，5.4，和12.2μM，分别地）比水飞蓟宾。甲基化衍生物的活性较低，效力最低的是3,7-二-O-甲基-2,3-脱氢水飞蓟宾（6）。另一方面，在C-7 OH和C-23 OH处的甲酰基化显着增加了细胞毒性以及对HUVEC增殖和迁移的影响。活性最高的衍生物是7 - O -galloyl-2,3-dehydrosilybin（13；在细胞毒性，增殖抑制和抗迁移试验中，IC 50值分别为3.4、1.6和4.7μM ）。总体而言，该初步的结构-活性关系研究表明，2,3-双键，C-7
• Mild and Selective Method of Bromination of Flavonoids
  作者：Martina Hurtová、David Biedermann、Marek Kuzma、Vladimír Křen

  DOI：10.1021/acs.jnatprod.0c00655

  日期：2020.11.25

  in good yields using α,β-dibromohydrocinnamic acid in the presence of a base. This procedure enables selective mono- or dibromination of compounds highly sensitive to oxidative or radical attack. New brominated derivatives of silymarin flavonolignans and related flavonoids were prepared. These brominated derivatives can be used as valuable synthetic intermediates in further synthesis.

  开发了一种在碱存在下使用 α,β-二溴氢化肉桂酸以良好收率温和选择性溴化简单芳香族化合物和黄酮类化合物的新方法。该程序能够对氧化或自由基攻击高度敏感的化合物进行选择性单溴化或二溴化。制备了水飞蓟素黄酮木脂素和相关黄酮类化合物的新型溴化衍生物。这些溴化衍生物可在进一步合成中用作有价值的合成中间体。
• O-Aminoalkyl-O-Trimethyl-2,3-Dehydrosilybins: Synthesis and In Vitro Effects Towards Prostate Cancer Cells
  作者：Bao Vue、Sheng Zhang、Andre Vignau、Guanglin Chen、Xiaojie Zhang、William Diaz、Qiang Zhang、Shilong Zheng、Guangdi Wang、Qiao-Hong Chen

  DOI：10.3390/molecules23123142

  日期：——

  As part of our ongoing silybin project, this study aims to introduce a basic nitrogen-containing group to 7-OH of 3,5,20-O-trimethyl-2,3-dehydrosilybin or 3-OH of 5,7,20-O-trimethyl-2,3-dehydrosilybin via an appropriate linker for in vitro evaluation as potential anti-prostate cancer agents. The synthetic approaches to 7-O-substituted-3,5,20-O-trimethyl-2,3-dehydrosilybins through a five-step procedure and to 3-O-substituted-5,7,20-O-trimethyl-2,3- dehydrosilybins via a four-step transformation have been developed. Thirty-two nitrogen-containing derivatives of silybin have been achieved through these synthetic methods for the evaluation of their antiproliferative activities towards both androgen-sensitive (LNCaP) and androgen-insensitive prostate cancer cell lines (PC-3 and DU145) using the WST-1 cell proliferation assay. These derivatives exhibited greater in vitro antiproliferative potency than silibinin. Among them, 11, 29, 31, 37, and 40 were identified as five optimal derivatives with IC50 values in the range of 1.40–3.06 µM, representing a 17- to 52-fold improvement in potency compared to silibinin. All these five optimal derivatives can arrest the PC-3 cell cycle in the G0/G1 phase and promote PC-3 cell apoptosis. Derivatives 11, 37, and 40 are more effective than 29 and 31 in activating PC-3 cell apoptosis.

  作为我们正在进行的水飞蓟素项目的一部分，这项研究旨在通过适当的连接剂将一种含氮基团引入3,5,20-O-三甲基-2,3-脱氢水飞蓟素的7-OH位置或者5,7,20-O-三甲基-2,3-脱氢水飞蓟素的3-OH位置，以进行体外评估作为潜在的抗前列腺癌药物。通过五步法合成了7-O取代的3,5,20-O-三甲基-2,3-脱氢水飞蓟素，通过四步转化合成了3-O取代的5,7,20-O-三甲基-2,3-脱氢水飞蓟素。通过这些合成方法，已经合成了32种含氮衍生物的水飞蓟素，用于评估它们对雄激素敏感（LNCaP）和雄激素非敏感前列腺癌细胞系（PC-3和DU145）的抗增殖活性，使用WST-1细胞增殖测定法。这些衍生物在体外表现出比水飞蓟素更强的抗增殖活性。其中，11、29、31、37和40被确定为五种优化的衍生物，其IC50值在1.40-3.06 µM范围内，与水飞蓟素相比，其效力提高了17-52倍。所有这五种优化的衍生物都能使PC-3细胞周期停滞在G0/G1期，并促进PC-3细胞凋亡。衍生物11、37和40在激活PC-3细胞凋亡方面比29和31更有效。
• Synthesis and Antiangiogenic Activity of New Silybin Galloyl Esters
  作者：Radek Gažák、Kateřina Valentová、Kateřina Fuksová、Petr Marhol、Marek Kuzma、Miguel Ángel Medina、Ivana Oborná、Jitka Ulrichová、Vladimír Křen

  DOI：10.1021/jm201034h

  日期：2011.10.27

  The synthesis of various silybin monogalloyl esters was developed, and their antiangiogenic activities were evaluated in a variety of in vitro tests with human umbilical vein endothelial cells (HUVECs). A structure activity relationship (SAR) study found the regioselectivity of the silybin galloylation to be highly significant. Silybin (as an equimolar mixture of two diastereomers A and B) exhibited quite poor antiangiogenic activities, whereas its El stereoisomer is more active than silybin A. The galloylation of phenolic OH groups of natural silybin (a mixture of both isomers) leads to increases in their antiangiogenic activities, which is more apparent with the 7-OH than the 20-OH. In contrast, gallates at aliphatic OH groups either had a comparable activity to the parent compound or are even worse than silybin, which was observed in the case of 3-O-galloylsilybin. The most effective compound from this series (7-O-galloylsilybin) has also been prepared from stereochemically pure silybins A and B to evaluate the effect of stereochemistry on the activity. As with silybin itself, the B isomer of 7-O-galloylsilybin was more active than A isomer.
• New derivatives of silybin and 2,3-dehydrosilybin and their cytotoxic and P-glycoprotein modulatory activity
  作者：Petr Džubák、Marián Hajdúch、Radek Gažák、Alena Svobodová、Jitka Psotová、Daniela Walterová、Petr Sedmera、Vladimír Křen

  DOI：10.1016/j.bmc.2006.01.035

  日期：2006.6

  Large series of O-alkyl derivatives (methyl and benzyl) of silybin and 2,3-dehydrosilybin was prepared. Selective alkylation of the silybin molecule was systematically investigated. For the first time we present here, for example, preparation of 19-nor-2,3-dehydrosilybin. All prepared silybin/2.3-dehydrosilybin derivatives were tested for cytotoxicity on a panel of drugs sensitive against multidrug resistant cell lines and the ability to inhibit P-glycoprotein mediated efflux activity. We have identified effective and relatively non-cytotoxic inhibitors of P-gp derived from 2,3-dehydrosilybin. Some of them were more effective inhibitors at concentrations lower than a standard P-gp efflux inhibitor cyclosporin A. Another group of 2,3-dehydrosilybin derivatives also had better inhibitory effects on P-gp efflux but a cytotoxicity comparable with that of parent 2,3-dehydrosilybin. Structural requirements for improving inhibitory activity and reducing toxicity of 2,3-dehydrosilybin were established. Effect of E-ring substitution as well as an influence of the substituent size at the C-7-OH position of A-ring on P-gp-inhibitory activity was evaluated for the first time in this study. (c) 2006 Elsevier Ltd. All rights reserved.