(-)-O-benzylarctigenine | 123251-05-8

• 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: (-)-O-benzylarctigenine
• 英文别名: (3R,4R)-4-[(3,4-dimethoxyphenyl)methyl]-3-[(3-methoxy-4-phenylmethoxyphenyl)methyl]oxolan-2-one
• CAS: 123251-05-8
• 化学式: C₂₈H₃₀O₆
• 分子量: 462.543
• InChiKey: XOLCTMMTFHXLNE-XZOQPEGZSA-N

物化性质

• 沸点：
  627.0±50.0 °C(Predicted)
• 密度：
  1.187±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  34
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  63.2
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (-)-O-benzylarctigenine 在 palladium 10% on activated carbon 、 氢气 作用下， 以 乙醇 为溶剂， 反应 0.5h， 以16%的产率得到牛蒡子苷元
  参考文献：
  名称：

  AMPA 和红藻氨酸受体拮抗剂牛蒡甙元类似物的合成和药理学表征

  摘要：

  (−)-Arctigenin 和一系列新类似物已被合成，然后使用 Ca 2+流入测定测试其作为 HEK293 细胞中表达的人同聚 GluA1 和 GluK2 受体的 AMPA 和红藻氨酸受体拮抗剂的潜力。一般来说，这些化合物对两种受体都显示出拮抗剂活性，并且对 AMPAR 的活性明显更高。 Schild 分析表明螺环类似物6c充当非竞争性拮抗剂。分子对接研究表明， 6c对接至 GluA2 四聚体的 X 射线晶体结构中，表明 (−)-牛蒡苷元及其类似物在跨膜结构域中的结合方式与已知的 AMPA 受体非竞争性拮抗剂 GYKI53655 和抗癫痫药吡仑帕奈。本文描述的牛蒡甙元衍生物可以作为开发治疗癫痫的药物的新先导物。

  DOI：

  10.1039/d1ob01653a
• 作为产物：
  描述：

  4-羟基-3-甲氧基苄醇 在 六甲基磷酰三胺 、 18-冠醚-6 、 三溴化磷 、 potassium carbonate 、 lithium diisopropyl amide 作用下， 以 乙醚 、 甲苯 为溶剂， 反应 19.5h， 生成 (-)-O-benzylarctigenine
  参考文献：
  名称：

  Intramolecular Regioselective Insertion into Unactivated Prochiral Carbon−Hydrogen Bonds with Diazoacetates of Primary Alcohols Catalyzed by Chiral Dirhodium(II) Carboxamidates. Highly Enantioselective Total Synthesis of Natural Lignan Lactones

  摘要：

  Intramolecular insertion into unactivated prochiral C-H bonds of 3-aryl-1-propyl diazoacetates catalyzed by dirhodium(II) tetrakis[methyl 1-(3-phenyl propanoyl)imidazolidin-2-one-4(R or S)-carboxylate], Rh-2(4R-MPPIM)(4) or Rh-2(4S-MPPIM)(4), occurs in 91-96% ee and with virtually complete regiocontrol for the formation of beta-benzyl-gamma-butyrolactones. This methodology has been applied to the total synthesis of dibenzylbutyrolactone lignans (-)- and (+)-enterolactone, (-)- and (+)-hinokinin, and (+)-arctigenin from substituted cinnamic acids in 19-27% overall yields. Aryltetralin lignan (+)-isodeoxypodophyllotoxin was prepared from the reactant 3,4-(methylenedioxy)cinnamic acid in 36% yield overall, and the lactone precursor to (+)-isolauricerisinol was formed in 96.5% ee and 23% yield overall. Applications of the chiral Rh-2(MPPIM)4 catalysts to fully aliphatic systems resulting in the formation of beta-substituted-gamma-butyrolactones with high regiocontrol and with 93-96% ee have demonstrated the generality of this methodology. A model that provides accurate predictions of beta-substituted-gamma-butyrolactone absolute configurations in these asymmetric metal carbene transformations is described.

  DOI：

  10.1021/jo961607u

文献信息

• 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（+）- 。
• Free-Radical-Mediated Conjugate Additions. Enantioselective Synthesis of Butyrolactone Natural Products:  (−)-Enterolactone, (−)-Arctigenin, (−)-Isoarctigenin, (−)-Nephrosteranic Acid, and (−)-Roccellaric Acid
  作者：Mukund P. Sibi、Pingrong Liu、Jianguo Ji、Saumen Hajra、Jian-xie Chen

  DOI：10.1021/jo015501x

  日期：2002.3.1

  alkylation furnished the natural products (-)-enterolactone, (-)-arctigenin, and (-)-isoarctigenin. The overall yields for the target natural products were 20-26% over six steps. Selective functionalization of the disubstituted succinates obtained by aldol condensation gave the paraconic acid natural products (-)-nephrosteranic acid (8) and (-)-roccellaric acid (9). The overall yield of the natural products

  路易斯酸介导的烷基向差异保护的富马酸酯10的共轭加成反应产生的单烷基化琥珀酸酯具有很高的化学效率和优异的立体选择性。随后的烷基化或醛醇缩合反应使二取代的琥珀酸酯具有顺式构型。手性助剂4-二苯基甲基-2-恶唑烷酮在两个步骤中控制立体选择性。通过烷基化获得的二取代琥珀酸酯的操作提供了天然产物（-）-内酯，（-）-arctigenin和（-）-异arctigenin。目标天然产物的总产率在六个步骤中为20-26％。通过醛醇缩合获得的二取代琥珀酸酯的选择性官能化得到对苯二酸天然产物（-）-肾甾酸（8）和（-）-二十二烷酸（9）。
• Total syntheses of (-)-trachelogenin, (-)-nortrachelogenin and (+)-wikstromol
  作者：Kenza Khamlach、Robert Dhal、Eric Brown

  DOI：10.1016/s0040-4039(00)99653-9

  日期：1989.1

  β-dibenzyl-γ-butyrolactones (lignans of synthetic origin), and were correlated to (±)-methyltrachelogenin 9 whose relative structure was definitely established by X-ray cristallography. (-)-Trachelogenin 1 and (-)-nortrachelogenin 12 thus have the (8S,8′S) absolute configuration, whereas (+)-nortrachelogenin 20 (or wikstromol) has the (8R,8′R) absolute configuration.

  通过相应的α，β-二苄基-γ-丁内酯（合成来源的木脂素）的α-羟基化获得标题化合物，并将其与（±）-甲基trachelogenin 9相关联，后者的相对结构通过X射线结晶成像法确定。因此，（-）-Trachelogenin 1和（-）-nortrachelogenin 12具有（8S，8'S）绝对构型，而（+）-nortrachelogenin 20（或wikstromol）具有（8R，8'R）绝对构型。
• 木脂素衍生物、其制备方法及用途
  申请人：中国科学院上海药物研究所

  公开号：CN115215821A

  公开（公告）日：2022-10-21

  本发明公开了一种木脂素衍生物、其制备方法及用途，所述木脂素衍生物结构如式I所示，式中，各取代基的定义如说明书和权利要求书中所述。本发明的木脂素衍生物，能够作为线粒体呼吸链复合物I抑制剂，抑制线粒体的氧化磷酸化作用及ATP的生成，用于预防和/或治疗与线粒体呼吸链复合物I活性或表达升高、或者线粒体氧化磷酸化作用增强相关的疾病。
• 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.