(±)-1-(4-hydroxy-3-methoxyphenyl)-(2R,3S)-dimethyl-4-(3,4-dimethoxyphenyl)butane

• 分子结构分类: 有机化合物 - 木脂素、新木脂素和相关化合物 - 二苄基丁烷木脂素
• 英文名称: (±)-1-(4-hydroxy-3-methoxyphenyl)-(2R,3S)-dimethyl-4-(3,4-dimethoxyphenyl)butane
• 英文别名: Meso-monomethyldihydroguaiaretic acid；4-[(2R,3S)-4-(3,4-dimethoxyphenyl)-2,3-dimethylbutyl]-2-methoxyphenol
• 化学式: C₂₁H₂₈O₄
• 分子量: 344.451
• InChiKey: NNYAKQAKXHZMKI-CABCVRRESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  25
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  47.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (±)-1-(4-hydroxy-3-methoxyphenyl)-(2R,3S)-dimethyl-4-(3,4-dimethoxyphenyl)butane 在 sodium methylate 、 potassium carbonate 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 生成 (+/-)-4-(3,4-dimethoxyphenyl)-1-[3-methoxy-4-[2-(2-nitro-1H-imidazol-1-yl)ethoxy]phenyl]-2,3-dimethylbutane
  参考文献：
  名称：

  肝细胞癌靶向剂：硝基咪唑与三甲基去甲氢愈创木酸的结合物

  摘要：

  几十年来，癌症一直是全球主要的健康问题，肝细胞癌（HCC）每年导致超过半百万新病例。五年后生存率低至<5％，它仍然是治疗不良的癌症。以前已证明抗氧化剂去氢双氢愈创木酸（NDGA）对癌细胞有效。硝基咪唑衍生物在缺氧条件下转化为反应性化合物。在这项研究中，合成了8个含有2或4个硝基咪唑部分的甲基化NDGA，作为抗HCC的先导。这些具有聚（乙二醇）系链的缀合物中的四种具有优异的水溶性。这四个NDGA硝基咪唑缀合物被发现抑制增殖HCC Hep3B细胞用IC 50个介于10和15μ值中号。此外，在低氧条件下，硝基咪唑共轭的NDGA衍生物具有更好的抗增殖活性。

  DOI：

  10.1002/cmdc.201300521
• 作为产物：
  描述：

  (6R,7R)-3-{4-[4-(3,4-Dimethoxy-phenyl)-2,3-dimethyl-butyl]-2-methoxy-phenoxymethyl}-5,8-dioxo-7-(2-phenoxy-acetylamino)-5λ⁴-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid 在 β-lactamase 作用下， 以 二甲基亚砜 为溶剂， 生成 (±)-1-(4-hydroxy-3-methoxyphenyl)-(2R,3S)-dimethyl-4-(3,4-dimethoxyphenyl)butane
  参考文献：
  名称：

  Design, synthesis, and biological evaluation of a cephalosporin–monohydroguaiaretic acid prodrug activated by a monoclonal antibody–β-lactamase conjugate

  摘要：

  A novel cephalosporin derivative of monohydroguaiaretic acid (cephem-M3N, 7) was synthesized and found to possess anticancer activity against human leukemia (K562), breast carcinoma (MCF7), human lung cancer (A549), human colon cancer (Colo205) and pancreatic cancer cells (Capan2 and MiaPaCa2). A tumor targeting fusion protein (dsFv3-beta-lactamase) was also used in conjunction with cephem-based M3N 7 and its potency toward K562, MCF7, A549, Colo205, Capan2. and MiaPaCa2 was found to approach that of the free M3N (4). In the presence of dsFv3-beta-lactamase. tumor cells were found to be much more susceptible to conjugate 7 than normal human embryonic lung (HEL) cells and normal fibroblasts (Hef522). These notions provide a new approach to the use of nordihydroguaiaretic acid (NDGA) and its derivatives for antitumor therapy. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(02)00140-2

文献信息

• meso-Dihydroguaiaretic acid derivatives with antibacterial and antimycobacterial activity
  作者：Karen Reyes-Melo、Abraham García、Antonio Romo-Mancillas、Elvira Garza-González、Verónica M. Rivas-Galindo、Luis D. Miranda、Javier Vargas-Villarreal、Juan Manuel J. Favela-Hernández、María del Rayo Camacho-Corona

  DOI：10.1016/j.bmc.2017.07.047

  日期：2017.10

  moderate activity against methicillin-resistant Staphylococcus aureus, whereas 30 and 31 showed better results than levofloxacin against vancomycin-resistant Enterococcus faecium. Additionally, nineteen meso-DGA derivatives displayed moderate to potent activity against M. tuberculosis H37Rv with minimum inhibitory concentration (MIC) values ranging from 3.125 to 50 µg/mL. Seven meso-DGA derivatives bearing

  三十三个内消旋-dihydroguaiaretic酸（内消旋承载酯，醚，和氨基-醚-DGA）衍生物的合成。所有衍生物均针对12株革兰氏阳性和革兰氏阴性细菌的耐药临床分离株进行了测试，包括敏感（H37Rv）和耐多药结核分枝杆菌菌株。在供试化合物，四个酯（7，11，13，和17），一个醚（23），和三个氨基醚（30，31，和33）显示出中度活性对耐甲氧西林金黄色葡萄球菌，而30和31对耐万古霉素的粪肠球菌的效果优于左氧氟沙星。此外，有19种内消旋-DGA衍生物对结核分枝杆菌H37Rv表现出中度至有效的活性，其最小抑菌浓度（MIC）值为3.125至50 µg / mL。七个带有氨基醚的内消旋-DGA衍生物（26 – 31和33）对结核分枝杆菌H37Rv和G122菌株表现出最低的MIC ，其中31个与乙胺丁醇一样有效（MIC为3.125和6.25 µg / mL）。具有立体和疏水特征的带正电荷的基团前体的存在（例如meso
• Antiviral Activities of Methylated Nordihydroguaiaretic Acids. 1. Synthesis, Structure Identification, and Inhibition of Tat-Regulated HIV Transactivation
  作者：Jih Ru Hwu、Wen Nan Tseng、John Gnabre、Paul Giza、Ru Chih C. Huang

  DOI：10.1021/jm970819w

  日期：1998.7.1

  Nordihydroguaiaretic acid (NDGA, meso-1) possesses four phenolic hydroxyl groups. Treatment of NDGA with 0.50-4.1 equiv of dimethyl sulfate and 3.0-6.0 equiv of potassium carbonate in acetone at 56 degrees C gave nine methylated products. Eight of those mono-, di-, tri-, and tetra-O-methylated NDGAs were isolated in pure form, and their structures were identified unambiguously by spectroscopic methods

  去甲二氢愈创木酸（NDGA，meso-1）具有四个酚羟基。在56℃下用0.50-4.1当量的硫酸二甲酯和3.0-6.0当量的碳酸钾在丙酮中处理NDGA，得到九种甲基化产物。单，二，三和四-O-甲基化的NDGA中有八种以纯净形式分离，并通过光谱法明确鉴定了它们的结构。通过使用4.1当量的硫酸二甲酯进行甲基化，以99％的产率从NDGA获得制备量的四甲基NDGA M4N（10）。在八个不同的甲基化NDGA（2-6和8-10）中，四-O-甲基-NDGA（10）显示出最强的抗HIV活性（IC50为11 microM）。化学合成的3'-O-甲基-NDGA（（+/-）-2）与从Creosote Bush分离的木脂素具有相同的抗HIV活性（IC50 25 microM）。具有甲基化的萘酚羟基的木质素可以低成本大量生产。在药物浓度低于30 microM时，四甲基NDGA（10）比单和二甲基化NDGA具有更强的抗HIV剂。
• Phenolic Compounds as Selective Antineoplasic Agents against Multidrug-resistant Human Cancer Cells
  作者：Noélia Duarte、Hermann Lage、Marta Abrantes、Maria-José Ferreira

  DOI：10.1055/s-0029-1240892

  日期：2010.7

  Twelve phenolic compounds, including three stilbenes, two flavonoids, two coumarins, one neolignan, and four lignans, isolated from Euphorbia and Pycnanthus species or obtained by derivatization, were assayed for their potential antineoplastic efficacy in three human cancer cell lines: gastric (EPG85-257), pancreatic (EPP85-181), and colon (HT-29) carcinomas as well as derived multidrug-resistant sublines. In each case, two different multidrug-resistant variants, i.e., cell lines with classical and atypical MDR phenotype, were used. The majority of the MDR cancer sublines showed increased sensitivities to the studied compounds when compared to the parental sublines. The most active compound was the flavonoid naringenin, found to be 15-fold more effective against the atypical MDR subline of gastric carcinoma than in parental drug-sensitive cells. Furthermore, the stilbene trans-3,5,3′,4′-tetramethoxypiceatannol and the lignans 4′-hydroxy-3,3′,4-trimethoxylignan and heliobuphthalmin also exhibited high antineoplasic activities against the classical MDR subline derived from gastric carcinoma. The results of this study suggest that some phenolic compounds might be valuable for the treatment of multidrug-resistant cancer cells.

  研究人员从大戟科植物和白千层属植物中分离或通过衍生化方法获得了 12 种酚类化合物，包括 3 种二苯乙烯类化合物、2 种黄酮类化合物、2 种香豆素类化合物、1 种新木质素类化合物和 4 种木质素类化合物，并对这 12 种化合物在胃癌（EPG85-257）、胰腺癌（EPP85-181）和结肠癌（HT-29）这三种人类癌症细胞系以及衍生的耐多药亚系中的潜在抗肿瘤功效进行了检测。每种情况都使用了两种不同的多重耐药变体，即具有典型和非典型多重耐药表型的细胞系。与亲本亚系相比，大多数 MDR 癌症亚系对所研究化合物的敏感性都有所提高。最有活性的化合物是类黄酮柚皮苷，它对非典型 MDR 胃癌亚系的疗效是对亲代药物敏感细胞的 15 倍。此外，二苯乙烯-反式-3,5,3′,4′-四甲氧基水飞蓟醇、木犀草素-4′-羟基-3,3′,4-三甲氧基木犀草素和七叶芹素也对源自胃癌的经典 MDR 亚系表现出很高的抗肿瘤活性。研究结果表明，一些酚类化合物可能对治疗耐多药癌细胞有价值。
• [EN] CONJUGATES OF NITROIMIDAZOLES AND THEIR USE AS CHEMOTHERAPEUTIC AGENTS<br/>[FR] CONJUGUÉS DE NITROIMIDAZOLES ET LEUR UTILISATION EN TANT QU'AGENTS CHIMIOTHÉRAPEUTIQUES
  申请人：UNIV JOHNS HOPKINS

  公开号：WO2012166778A3

  公开（公告）日：2013-03-14
• Hepatocellular Carcinoma Targeting Agents: Conjugates of Nitroimidazoles with Trimethyl Nordihydroguaiaretic Acid
  作者：Ming-Hua Hsu、Szu-Chun Wu、Kuan-Chuan Pao、Irem Unlu、John N. Gnabre、David E. Mold、Ru Chih C. Huang、Jih Ru Hwu

  DOI：10.1002/cmdc.201300521

  日期：2014.5

  methylated NDGAs containing a 2‐ or 4‐nitroimidazole moiety were synthesized as leads against HCC. Four of these conjugates, possessing a poly(ethylene glycol) tether, had superior aqueous solubility. These four NDGA–nitroimidazole conjugates were found to inhibit the proliferation HCC Hep3B cells with IC50 values between 10 and 15 μM. Furthermore, nitroimidazole‐conjugated NDGA derivatives exhibit better

  几十年来，癌症一直是全球主要的健康问题，肝细胞癌（HCC）每年导致超过半百万新病例。五年后生存率低至<5％，它仍然是治疗不良的癌症。以前已证明抗氧化剂去氢双氢愈创木酸（NDGA）对癌细胞有效。硝基咪唑衍生物在缺氧条件下转化为反应性化合物。在这项研究中，合成了8个含有2或4个硝基咪唑部分的甲基化NDGA，作为抗HCC的先导。这些具有聚（乙二醇）系链的缀合物中的四种具有优异的水溶性。这四个NDGA硝基咪唑缀合物被发现抑制增殖HCC Hep3B细胞用IC 50个介于10和15μ值中号。此外，在低氧条件下，硝基咪唑共轭的NDGA衍生物具有更好的抗增殖活性。