dioncophylline A | 60142-17-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异喹啉及其衍生物
• 英文名称: dioncophylline A
• 英文别名: (1R,3R)-7-(4,5-dimethoxy-2-methylnaphthalen-1-yl)-1,3-dimethyl-1,2,3,4-tetrahydroisoquinolin-8-ol
• CAS: 60142-17-8；68780-11-0；129519-17-1；129567-02-8
• 化学式: C₂₄H₂₇NO₃
• 分子量: 377.483
• InChiKey: MXIZZLBQRBAZEX-HUUCEWRRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  28
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  50.7
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  dioncophylline A 以39%的产率得到
  参考文献：
  名称：

  BRINGMANN, GERHARD;RUBENACKER, MARTIN;JANSEN, JOHANNES R.;SCHEUTZOW, DIET+, TETRAHEDRON LETT., 31,(1990) N, C. 639-642

  摘要：

  DOI：
• 作为产物：
  描述：

  (1R,3R)-2-Benzyl-8-methoxy-1,3-dimethyl-1,2,3,4-tetrahydro-isoquinolin-6-ol 生成 dioncophylline A
  参考文献：
  名称：

  BRINGMANN, GERHARD;JANSEN, JOHANNES R.;REUSCHER, HELMUT;RUBENACKER, MARTI+, TETRAHEDRON LETT., 31,(1990) N, C. 643-646

  摘要：

  DOI：

文献信息

• <i>N,N</i>-Dimethyldioncophyllinium A Iodide: Synthesis, Stereoanalysis, and Antimalarial Activity of the First<i>N</i>-Quaternary Naphthylisoquinolinium Salt*
  作者：Gerhard Bringmann、Michael Ochse、Manuela Schäffer、Ralf God、Rainer Walter、Guido François

  DOI：10.1055/s-2006-957760

  日期：1997.12

  The first synthesis of an N-quaternary salt of a naphthylisoquinoline alkaloid, N,N-dimethyldioncophyllinium A iodide, is described. For this potential natural product, a degradative procedure for the unambiguous stereoanalysis of the stereogenic centers has been elaborated. It shows enhanced anti-plasmodial activity in vitro towards Plasmodium falciparum erythrocytic forms, as compared to its less methylated precursors.

  本研究首次合成了一种萘基异喹啉生物碱的 N-季铵盐--N,N-二甲基二月叶碱 A 碘化物。针对这种潜在的天然产物，我们详细阐述了一种降解程序，用于对立体中心进行明确的立体分析。与甲基化程度较低的前体相比，它在体外对恶性疟原虫红细胞形式的抗疟活性更强。
• Jozimine A₂: The First Dimeric Dioncophyllaceae-Type Naphthylisoquinoline Alkaloid, with Three Chiral Axes and High Antiplasmodial Activity
  作者：Gerhard Bringmann、Guoliang Zhang、Tobias Büttner、Gabi Bauckmann、Thomas Kupfer、Holger Braunschweig、Reto Brun、Virima Mudogo

  DOI：10.1002/chem.201202755

  日期：2013.1.14

  that is, lacking oxygen functions at C6, and bearing R configurations at C3 in its two isoquinoline portions. Despite this decreased steric hindrance, the outer biaryl axes are chiral, too, so that jozimine A2 (2) has three consecutive stereogenic axes and, together with the four stereogenic centers, seven elements of chirality and is C2‐symmetric. The new dimer exhibits excellent, and specific, antiplasmodial

  从刚果民主共和国的Ancistrocladus物种的根皮中分离出一种新的二聚萘基异喹啉碱生物碱，Jozimine A 2（2）。它的绝对立体结构是通过化学，光谱和按摩方法确定的，并通过X射线晶体学证实。Jozimine A 2（2）是一种非常罕见的萘基异喹啉二聚体之一，其中心联芳基轴受到旋转阻碍。此外，它是Dioncophyllaceae型生物碱的第一个天然二聚体，即在C6处缺乏氧功能，且带有R在C3的两个异喹啉部分中的构型。尽管减少了空间位阻，但联芳基的外部轴也是手性的，因此，Jozimine A 2（2）具有三个连续的立体轴，以及四个立体中心，具有七个手性元素，并且是C 2对称的。新的二聚体表现出优异的特异性抗疟原虫活性。为了进一步确认其立体结构并同样对其（非天然）阻转异构体的生物活性进行测试，化合物2是通过同时存在（同样可合成获得的）二茶碱A（5）及其阻转剂半合成而制得的。非对映异构体，3′-
• Jozimine A (‘dimeric’ dioncophylline A), a non-natural michellamine analog with high antimalarial activity
  作者：Gerhard Bringmann、Wael Saeb、Dagmar Koppler、Guido François

  DOI：10.1016/0040-4020(96)00812-5

  日期：1996.10

  described, starting from dioncophylline A, as isolated from Triphophyllum peltatum, resp. prepared by total synthesis. It is the first dimeric naphthylisoquinoline alkaloid that displays distinct antimalarial activity (IC50 = 0.075 μg/ml) against asexual erythrocytic stages of Plasmodium falciparum, which even exceeds the activity of its monomeric precursor, dioncophylline A (IC50 = 1.44 μg/ml), and

  描述了Jozimine A的合成，Jozimine A是天然存在的单体萘基异喹啉碱生物碱的第一个非天然二聚体，其起始于二壬基茶碱A，其是从白果苦瓜中分离得到的。通过全合成制备。这是首个二聚萘基异喹啉生物碱，对恶性疟原虫的无性红细胞阶段表现出独特的抗疟疾活性（IC 50 = 0.075μg/ ml），甚至超过了其单体前体双糖茶碱A的活性（IC 50 = 1.44μg / ml）。 ，因此构成了新型的抗疟疾季戊四烯基。
• Synthesis and Pharmacological Evaluation of Fluorescent and Photoactivatable Analogues of Antiplasmodial Naphthylisoquinolines
  作者：Gerhard Bringmann、Christian M. Gampe、Yanina Reichert、Torsten Bruhn、Johan H. Faber、Martin Mikyna、Matthias Reichert、Matthias Leippe、Reto Brun、Christoph Gelhaus

  DOI：10.1021/jm061464w

  日期：2007.11.1

  The naphthylisoquinoline (NIQ) alkaloids from tropical Ancistrocladaceae and Dioncophyllaceae plants show high antiplasmodial activities in vitro and in vivo, even against chloroquine-resistant strains of the malaria pathogen. For the directed optimization of these activities, an investigation of the mode of action seems most rewarding. We have therefore embarked on the identification of the respective target protein in Plasmodium falciparum. For this purpose, we have developed a flexible pathway for the synthesis of a chemically divergent series of photoactive and fluorescent derivatives of such alkaloids and succeeded in preparing the first functionalized NIQ derivatives, 10, 12, and 35, suited for fluorescence and photoaffinity labeling experiments. Pharmacological investigations ensured that the modified alkaloid derivatives retained their antiplasmodial activity. The work may pave the way for a further improvement of the activity of these natural products and will thus increase their pharmacological potential as a valuable lead structure against the widespread tropical disease malaria.
• Dioncophylline A as a Growth-Retarding Agent against the Herbivorous Insect <i>Spodoptera littoralis</i>:  Structure−Activity Relationships
  作者：Gerhard Bringmann、Jörg Holenz、Birgit Wiesen、Bambang W. Nugroho、Peter Proksch

  DOI：10.1021/np960707s

  日期：1997.4.1

  Dioncophylline A (1) represents a novel insecticidal agent, as documented by its enhanced growth-retarding effect on larvae of the polyphagous pest insect Spodoptera littoralis. Within the scope of the work described here, the potential of this as yet most active naphthylisoquinoline alkaloid was further elucidated by the preparation and testing of selected analogues. Investigation of a broad series of structurally modified dioncophylline A analogues (2-20) revealed the free amine function to be essential for the growth inhibitory effect, whereas a modification of the OH function partially led to a distinct increase of activity. In particular, the 8-O-alkyl (especially 8-O-benzylated) derivatives (14 and 15 as well as 16-19) displayed pronounced effects. In the case of 8-O-(p-bromobenzyl)dioncophylline A (16), the activity of the natural parent compound dioncophylline A (1) (EC50 = 277 mu g/g fresh wt of diet; concentration that inhibits larval growth by 50%) was even improved by a factor of >15 (EC50 = 15.6 mu g/g fresh wt).