(-)-cubebin

• 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: (-)-cubebin
• 英文别名: (3S,4S)-3,4-bis(1,3-benzodioxol-5-ylmethyl)oxolan-2-ol
• 化学式: C₂₀H₂₀O₆
• 分子量: 356.375
• InChiKey: DIYWRNLYKJKHAM-FKTKBCEVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  66.4
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (-)-cubebin 在 sodium tetrahydroborate 作用下， 以 甲醇 为溶剂， 反应 24.0h， 以88%的产率得到(S,S)-(+)-3,4-bis[3,4-(methylenedioxy)benzyl]-1,4-butanediol
  参考文献：
  名称：

  Anticancer activity studies of cubebin isolated from Piper cubeba and its synthetic derivatives

  摘要：

  (-)-Cubebin是从Piper cubeba的种子中分离出来的，其五种不同类型的衍生物（总计17种）具有不同的官能团。通过MTT法对这六种化合物在体外对六个人类癌细胞系（A549、K562、SiHa、KB、HCT116 和HT29）的抗肿瘤活性进行了测试。Cubebin及其含有内酯和酰胺基团的衍生物显示出显著的抗肿瘤活性。在某些测试的细胞系中，酰胺衍生物表现出更高的活性。形态学分析表明，这些化合物通过凋亡介导的细胞死亡途径发挥作用，我们预期这些结果将为通过(-)-Cubebin的衍生物开发新型抗肿瘤药物铺平道路。(C) 2016 Elsevier Ltd. 保留所有权利。

  DOI：

  10.1016/j.bmcl.2016.02.041
• 作为产物：
  描述：

  3-[3,4-(亚甲二氧基)苯基]丙酸 在 sodium periodate 、 四氧化锇 、 lithium aluminium tetrahydride 、 草酰氯 、 titanium(IV) chloride tetrahydrofuran 、 N-甲基吗啉氧化物 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 、 叔丁醇 为溶剂， 反应 145.84h， 生成 (-)-cubebin
  参考文献：
  名称：

  5-羟甲基二苄基丁内酯及相关木脂素的模块化合成及生物学研究

  摘要：

  二苄基丁内酯木脂素以其优异的生物学特性而闻名，特别是其显着的抗增殖活性。在此，我们报告了一种利用酰基-克莱森重排立体选择性制备关键中间体的二苄基丁内酯木脂素的新型、高效、会聚合成。报道的合成路线能够修饰这些木脂素以产生这些木脂素的 5-羟甲基衍生物。评估了这些类似物的生物活性，其衍生物显示出优异的细胞毒性特征，导致 Jurkat T 白血病细胞程序性细胞死亡，其中不到 2% 的孵育细胞进入坏死细胞死亡途径。

  DOI：

  10.3390/molecules23123057

文献信息

• Synthesis and biological activity evaluation of lignan lactones derived from (−)-cubebin
  作者：Rosangela da Silva、Gustavo H.B. de Souza、Ademar A. da Silva、Vanessa A. de Souza、Ana C. Pereira、Vanesa de A. Royo、Marcio L.A. e Silva、Paulo M. Donate、Ana L.S. de Matos Araújo、José C.T. Carvalho、Jairo K. Bastos

  DOI：10.1016/j.bmcl.2004.12.035

  日期：2005.2

  The anti-inflammatory and analgesic effects of three dibenzylbutyrolactone lignans, (-)-hinokinin (2), (-)-6,6'-dinitrohinokinin (3), and (-)-6,6'-diaminohinokinin (4), obtained by partial synthesis from (-)-cubebin (1), were investigated using different animal models. It was observed that compounds (1) and (2) inhibited the edema formation in the rat paw edema assay at the same level and that all

  三种二苄基丁内酯木脂素，（-）-hinokinin（2），（-）-6,6'-dinitrohinokinin（3）和（-）-6,6'-diaminohinokinin（4）的抗炎和镇痛作用，使用不同的动物模型研究了从（-）-立方蛋白（1）的部分合成中获得的蛋白质。观察到化合物（1）和（2）在大鼠爪水肿测定中以相同水平抑制水肿形成，并且所有反应均是剂量依赖性的。同样，在实验的第三小时，以30 mg / kg的剂量，化合物1、2、3和4分别抑制水肿形成53％，63％，54％和82％。在乙酸引起的小鼠扭体试验中，化合物2和4的抑制水平分别为97％和92％，而化合物3的抑制作用较低（75％），仍高于1。
• In vivo and in silico anti-inflammatory mechanism of action of the semisynthetic (−)-cubebin derivatives (−)-hinokinin and (−)-O-benzylcubebin
  作者：Thaís C. Lima、Rodrigo Lucarini、Angelica C. Volpe、Carolina Q.J. de Andrade、Alice M.P. Souza、Patricia M. Pauletti、Ana H. Januário、Guilherme V. Símaro、Jairo K. Bastos、Wilson R. Cunha、Alexandre Borges、Rosangela da Silva Laurentiz、Valéria A. Conforti、Renato L.T. Parreira、Carly H.G. Borges、Giovanni F. Caramori、Karla F. Andriani、Márcio L.A. e Silva

  DOI：10.1016/j.bmcl.2016.11.081

  日期：2017.1

  (−)-Cubebin (CUB), isolated from seeds of Piper cubeba, was used as starting material to obtain the derivatives (−)-hinokinin (HK) and (−)-O-benzyl cubebin (OBZ). Using paw edema as the experimental model and different chemical mediators (prostaglandin and dextran), it was observed that both derivatives were active in comparison with both negative (5% Tween® 80 in saline) and positive (indomethacin)

  （-）-Cubebin（CUB），从胡椒胡椒种子中分离用作原料，得到衍生物（-）-日激肽（HK）和（-）-O-苄基立方蛋白（OBZ）。使用爪水肿作为实验模型并使用不同的化学介质（前列腺素和右旋糖酐），与阴性对照（盐水中的80％吐温80）和阳性对照（吲哚美辛）相比，这两种衍生物均具有活性。OBZ（66.0％）达到了前列腺素引起的水肿的最大减少，而HK导致了59.2％的减少。尽管如此，两种衍生物（HK或OBZ）均未显着降低右旋糖酐诱导的爪水肿，与阳性对照赛庚啶相比，右旋赛庚啶可分别抑制水肿形成18.3％和3.5％。 56.0％。
• Trypanocidal activity of (−)-cubebin derivatives against free amastigote forms of Trypanosoma cruzi
  作者：Vanessa A. de Souza、Rosangela da Silva、Ana C. Pereira、Vanessa de A. Royo、Juliana Saraiva、Marisa Montanheiro、Gustavo H.B. de Souza、Ademar A. da Silva Filho、Marcella D. Grando、Paulo M. Donate、Jairo K. Bastos、Sérgio Albuquerque、Márcio L.A. e Silva

  DOI：10.1016/j.bmcl.2004.10.079

  日期：2005.1

  Five (-)-cubebin derivative compounds, (-)-O-acetyl cubebin (3), (-)-O-benzyl cubebin (4), (-)-O-(N,N-dimethylaminoethyl)-cubebin (5), (-)-hinokinin (6) and (-)-6,6'-dinitrohinokinin (7), previously synthesised by our research group, were evaluated on in vitro assay against free amastigote forms of Trypanosoina cruzi, the asogic agent of Chagas' disease. It was observed that 6 was the most active compound (IC50 = 0.7 muM), and that 4 and 5 displayed moderate activity against the parasite, giving IC50 values of 5.7 and 4.7 muM, respectively. In contrast, it was observed that compound 3 was inactive and that 7 displayed low activity with IC50 values of congruent to1.5 x 10(4) and 95.3 muM, respectively. (C) 2004 Elsevier Ltd. All rights reserved.
• Coimbra, H dos S; Royo; de Souza, Bollettino Chimico Farmaceutico, 2004, vol. 143, # 2, p. 65 - 69
  作者：Coimbra, H dos S、Royo、de Souza、Pereira、de Souza、da Silva、Donate、Silva、Cunha、Carvalho、Bastos

  DOI：——

  日期：——
• Process To Obtain Dibenzylbutyrolactonic, Tetrahydrofuranic Lignans And Their Synthetic And Semi-Synthetic Derivatives, Their Analgesic And Anti-Inflammatory Activities, Topical And/Or Systemic Formulations Containing Said Lignans And Their Respective Therapeutic Method
  申请人：Silva Marcio Luis Andrade e

  公开号：US20080214661A1

  公开（公告）日：2008-09-04

  A process to obtain dibenzylbutyrolactonic lignans from (-)-cubebin, isolated from a Piperaceae, especially Piper cubeba, and from (-)-methylpluviatolide, isolated from a Rutacea, especially Zanthoxylum naranjillo; their synthetic and semi-synthetic derivatives and tetrahydrofuranic lignans, such as galgravin and veragensin, isolated from Nectandra megapotamica, as well as the analgesic and anti-inflammatory activities of said lignans, and the topical and/or systemic formulations. Also presented is a therapeutic method using topic and/or systemic formulations based on said lignans for the treatment of inflammation and/or pain. Further, a process to obtain synthetic and semi-synthetic derivatives of (-)-cubebin, such as: (-)—O-acetyl cubebin; (-)—O-methyl cubebin; (-)—O—(N,N-dimethylamino-ethyl)-cubebin; (-)-hinokinin; (-)- 6,6 ′-dinitroinokinin; (-)—O-benzyl cubebin; (-)- 6,6 ′-diaminohinokinin and other synthetic derivatives which may be obtained, and synthetic and semi-synthetic derivatives of (-)-methylpluviatolide, such as (-)- 6,6 ′-dinitromethylpluviatolide and (-)- 6,6 ′-diaminomethylpluviatolide, to be used in the manufacture of medicine that has analgesic and anti-inflammatory activity is presented.