brassilignan | 62624-76-4

• 分子结构分类: 有机化合物 - 木脂素、新木脂素和相关化合物 - 呋喃类木脂素
• 英文名称: brassilignan
• 英文别名: Trans-3,4-bis(3,4-dimethoxybenzyl)tetrahydrofuran；(3R,4R)-3,4-bis[(3,4-dimethoxyphenyl)methyl]oxolane
• CAS: 62624-76-4
• 化学式: C₂₂H₂₈O₅
• 分子量: 372.461
• InChiKey: DMDLIQAXFOCGBP-ROUUACIJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  27
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  46.2
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  brassilignan 在 thallium (III) oxide 、 三氟乙酸 作用下， 反应 0.5h， 以86%的产率得到(2R)-(8β,8'α)-9,9'-epoxy-4,5,4',5'-tetramethoxy-2,2'-cyclolignane
  参考文献：
  名称：

  Buckleton, John S.; Cambie, Richard C.; Clark, George R., Australian Journal of Chemistry, 1988, vol. 41, # 3, p. 305 - 324

  摘要：

  DOI：
• 作为产物：
  描述：

  3,4-二甲氧基苯甲醛肟 在 palladium on activated charcoal 、 W-2 Ra-Ni 吡啶 、 N-氯代丁二酰亚胺 、 正丁基锂 、 硫酸 、 甲基锂 、 氢气 、 硼酸 、 potassium carbonate 、 三乙胺 作用下， 以 甲醇 、 乙醇 、 水 为溶剂， 反应 70.5h， 生成 brassilignan
  参考文献：
  名称：

  Enantiocontrolled synthesis of burseran, brassilignan, dehydroxycubebin, and other tetrahydrofuran lignans in both enantiomeric forms. Application of intermolecular nitrile oxide cycloadditions and lipase-mediated kinetic resolutions

  摘要：

  Several natural and unnatural tetrahydrofuran lignans have been synthesized by a convergent approach. Our methodology utilizes a nitrile oxide cycloaddition to dihydrofuran 8 and an enzymatic resolution of alcohols 11 by lipase PS. The lipase-mediated kinetic resolution of alcohols 11 furnished both enantiomers of the lignan precursors 12 and 14 in high optical purity (>99% ee). This is followed by a S(N)2 displacement of tosylates 15 and 18 by alpha-lithiobenzyl phenyl sulfides. In this manner, both enantiomers of 3,4-dibenzyltetrahydrofuran (17a, 20a), 3,4-bis(3-methoxybenzyl)-tetrahydrofuran (17b, 20b), brassilignan (17c, 20c), dehydroxycubebin (17d, 20d), and burseran (17e, 20e) were synthesized in overall yields of 6-16%.

  DOI：

  10.1021/jo00060a037

文献信息

• Capricious Selectivity in Electrophilic Deuteration of Methylenedioxy Substituted Aromatic Compounds
  作者：Monika Pohjoispää、Raúl Mera-Adasme、Dage Sundholm、Sami Heikkinen、Tapio Hase、Kristiina Wähälä

  DOI：10.1021/jo5019427

  日期：2014.11.7

  Ring deuteration via the SEAr mechanism, which is usually problem-free, is found to be troublesome with methylenedioxy substituent aromatics. We report a case where the deuteration not only partially fails at one of the ortho positions but also is completely prevented by a conformation dependent effect at the other o-position. Such selectivity discrepancies are important due to the widespread occurrence

  发现通过S E Ar机制的环氘化通常是没有问题的，但是对于亚甲二氧基取代基芳族化合物来说是麻烦的。我们报道了一种情况，其中氘不仅在邻位之一处部分失效，而且在另一o位处构象依赖性效应完全阻止了氘化。由于亚甲二氧基取代的天然产物的广泛存在，这种选择性差异很重要。密度泛函理论计算用于阐明1,2-二烷氧基苯中的交换反应机理。
• Lignames
  作者：Eric Brown、Alain Daugan

  DOI：10.1016/0040-4020(89)80041-9

  日期：1989.1

  following two lactones were obtained in both (R)-(+) and (S)-(−) enantiomeric forms, β-piperonyl- and β-veratryl-γ-butyrolactones and respectively. These lactones were used as key-intermediates for the syntheses of 17 optically active lignans and lignoids, such as (-1-dimethylmatairesinol (−)-, (−)-kusunokinin (−)- and (+)-diniethylisolariciresinol (+)-.

  描述了导致光学活性的β-苄基-γ-丁内酯的简单而有效的途径。因此，由Stobbe与适当的芳族醛缩合，然后催化氢化中间体α-亚苄基半琥珀酸酯而得到的（R，S）-α-苄基双琥珀酸甲酯，通过手性碱（麻黄碱或α-乙胺基）。使用硼氢化钙还原每种对映异构体，然后得到相应的旋光性β-苄基-γ-丁内酯。以此方式，以（R）-（+）和（S）-（-）对映体形式获得以下两个内酯，β-哌啶基-和β-藜芦基-γ-丁内酯和分别。这些内酯用作合成17种旋光性木脂素和木质素的关键中间体，例如（-1-二甲基麦芽甾醇（-）- ，（-）-苦参素（-）-和（+）-二乙基异芳基树脂（+）- 。
• Synthesis and applications of diphosphine ligands derived from the lignan hydroxymatairesinol
  作者：Yury Brusentsev、Patrik Eklund

  DOI：10.1016/j.cattod.2014.02.032

  日期：2015.3

  to DIOP were developed. Catalytic activity and induction of enantioselectivity for the prepared phosphines were evaluated in rhodium catalyzed hydrogenations of different functionalized alkenes. High catalytic activities were observed with low catalyst loading at atmospheric pressure. The phosphines showed moderate to high enantioselectivity depending on the substrate used. Hydrogenation of 1-acetamidostyrene

  开发了一种高效的方法，用于将天然木脂素羟基苦参醇合成修饰为类似于DIOP的手性二膦。在铑催化的不同官能化烯烃的加氢反应中，对制备的膦的催化活性和对映选择性的诱导进行了评估。在大气压下以低催化剂负载观察到高催化活性。根据所使用的底物，膦显示出中等至高的对映选择性。1-乙酰氨基苯乙烯的氢化得到84％ee的S-对映体。
• Chemistry of the podocarpaceae—III
  作者：L.H. Briggs、R.C. Cambie、J.L. Hoare

  DOI：10.1016/s0040-4020(01)93195-3

  日期：1959.1

  A new lignan for which the name seco-isolariciresinol is proposed, has been isolated from the heartwood of Podocarpus spicatus. The structure has been shown to be 2:3-bis(4′-hydroxy-3′- methoxybenzyl)-butan-1:4-diol (II, R = H), and confirmed by an absolute synthesis from (−)-matairesinol (I, R = H). A further examination of the extractives of the heartwood has resulted in the isolation of the minor

  从罗汉松的心材中分离出一种新的木脂素，提出了新的木酚素，其名称为癸二-异西里香脂醇。已经显示该结构为2：3-双（4'-羟基-3'-甲氧基苄基）-丁丹-1：4-二醇（II，R = H），并且通过从（-）-的绝对合成来证实。苦参醇（I，R = H）。对心材提取物的进一步检查导致除先前报道的化合物马蒂固醇，α-榄香烯苷，槲皮素之外，还分离了次要成分（+）-紫杉醇，（+）-芳香金属菊酯，山奈酚和角豆蔻醇。 ，金雀异黄素和popopicatin。
• Design, Semisynthesis, and Estrogenic Activity of Lignan Derivatives from Natural Dibenzylbutyrolactones
  作者：Priscila López-Rojas、Ángel Amesty、Miguel Guerra-Rodríguez、Yeray Brito-Casillas、Borja Guerra、Leandro Fernández-Pérez、Ana Estévez-Braun

  DOI：10.3390/ph15050585

  日期：——

  Based on molecular docking studies on the ERα, a series of lignan derivatives (3–16) were designed and semisynthesized from the natural dibenzylbutyrolactones bursehernin (1) and matairesinol dimethyl ether (2). To examine their estrogenic and antiestrogenic potencies, the effects of these compounds on estrogen receptor element (ERE)-driven reporter gene expression and viability in human ER+ breast cancer cells were evaluated. Lignan compounds induced ERE-driven reporter gene expression with very low potency as compared with the pure agonist E2. However, coincubation of 5 μM of lignan derivatives 1, 3, 4, 7, 8, 9, 11, 13, and 14 with increasing concentrations of E2 (from 0.01 pM to 1 nM) reduced both the potency and efficacy of pure agonists. The binding to the rhERα-LBD was validated by TR-FRET competitive binding assay and lignans bound to the rhERα with IC50 values from 0.16 μM (compound 14) to 6 μM (compound 4). Induced fit docking (IFD) and molecular dynamics (MD) simulations for compound 14 were carried out to further investigate the binding mode interactions. Finally, the in silico ADME predictions indicated that the most potent lignan derivatives exhibited good drug-likeness.

  基于对ERα的分子对接研究，一系列木脂素衍生物（3-16）从天然的二苯基丁酸内酯bursehernin（1）和matairesinol二甲醚（2）中设计并半合成。为了检查它们的雌激素和抗雌激素效力，评估了这些化合物对ER+人类乳腺癌细胞中ER元件驱动的报告基因表达和细胞生存率的影响。与纯激动剂E2相比，木脂素化合物诱导的ER元件驱动的报告基因表达的效力非常低。然而，在5μM的木脂素衍生物1、3、4、7、8、9、11、13和14的共孵育下，随着E2浓度（从0.01 pM到1 nM）的增加，纯激动剂的效力和效能均降低。通过TR-FRET竞争结合测定验证了与rhERα-LBD的结合，并且木脂素与rhERα的IC50值从0.16μM（化合物14）到6μM（化合物4）不等。对于化合物14，进行了诱导适应性对接（IFD）和分子动力学（MD）模拟以进一步研究结合模式和相互作用。最后，计算机辅助预测ADME表明，最有效的木脂素衍生物表现出良好的药物相似性。