(-)-Aporphine

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 阿朴菲
• 英文名称: (-)-Aporphine
• 英文别名: (+)-dihydropontevedrine；(R)-(-)-aporphine；aporphine；(R)-6-Methyl-5,6,6a,7-tetrahydro-4H-dibenzo[de,g]quinoline；(6aR)-6-methyl-5,6,6a,7-tetrahydro-4H-dibenzo[de,g]quinoline
• 化学式: C₁₇H₁₇N
• 分子量: 235.329
• InChiKey: BZKUYNBAFQJRDM-MRXNPFEDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  18
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  3.2
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为产物：
  描述：

  Trifluoro-methanesulfonic acid (R)-6-methyl-5,6,6a,7-tetrahydro-4H-dibenzo[de,g]quinolin-11-yl ester 在 bis-triphenylphosphine-palladium(II) chloride 、 甲酸 、 三正丁胺 、 二苯基丙基膦 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.25h， 生成 (-)-Aporphine
  参考文献：
  名称：

  11-Substituted (R)-Aporphines:  Synthesis, Pharmacology, and Modeling of D_2A and 5-HT_1A Receptor Interactions

  摘要：

  A series of C11-substituted (R)-aporphines and C11-oxygenated (R)-noraporphines has been synthesized and evaluated for central serotonergic and dopaminergic effects in vitro and in vivo. The various C11-substituents were introduced using efficient nickel- and palladium-catalyzed reactions of the corresponding triflate (R)-11-[[(trifluoromethyl)sulfonyl]oxy] aporphine (6), Several compounds display high affinity to serotonin 5-HT1A receptors in spite of major differences in steric bulk and electronic properties of the various C11-substituents. A change of the N-methyl group of the nonselective 3 to H [23, (R)-11-hydroxynoraporphine] or propyl [2, (R)-11-hydroxy-N-propylnoraporphine] increases the selectivity for 5-HT1A receptors (100-fold) and dopamine D-2A receptors (3-fold), respectively. Compounds 3 and 23 have similar affinities to 5-HT1A receptors, whereas the propyl substituent of 2 not only enhances the selectivity for D-2A receptors but also increases the D-2A affinity. Modeling of ligand-receptor binding site interactions yielded an interaction site model for the 5-HT1A receptor that describes a gradual change in binding mode for C11-hydroxy, -methoxy-, and -phenyl-substituted derivatives. Hydrogen bonding is hereby gradually replaced by van der Waals interactions involving a relatively large lipophilic pocket. The derived D-2A receptor model can accommodate both the N-propyl substituent of 2 and the C11-ethyl substituent of 11 [(R)-11-ethylaporphine].

  DOI：

  10.1021/jm960189i

文献信息

• Racemization of (S)-(+)-10,11-dimethoxyaporphine and (S)-(+)-aporphine: efficient preparations of (R)-(−)-apomorphine and (R)-(−)-aporphine via a recycle process of resolution
  作者：Xiao-Xin Shi、Feng Ni、Hai-Xia Shang、Ming-Le Yan、Jun-Quan Su

  DOI：10.1016/j.tetasy.2006.08.005

  日期：2006.9

  Efficient preparations of (R)-(−)-apomorphine (R)-1 and (R)-(−)-aporphine (R)-2 based on a recycle process of resolution are described. In this recycle process of resolution, (RS)-(±)-10,11-dimethoxyaporphine 3 as the precursor of 1, and (RS)-(±)-aporphine 2 were successfully resolved into both enantiomers with (+)-dibenzoyltartaric acid (DBTA). The desired (R)-3 and (R)-2 were obtained and then, respectively

  的有效制剂（[R ）- （ - ） -阿扑吗啡（[R ）- 1和（- [R ）- （ - ） -阿朴啡（[R ） - 2基于分辨率的循环方法进行说明。在该拆分的循环过程中，将（RS）-（±）-10,11-二甲氧基阿福啡3作为1的前体，将（RS）-（±）-阿福啡2成功地拆分为两种具有（+）-二苯甲酰基酒石酸的对映体酸（DBTA）。获得所需的（R）-3和（R）-2，然后分别转化为化合物（R）-1，（R）-1的盐酸盐，二乙酸化合物4和（R）-2的盐酸盐; 将不需要的（S）-3和（S）-2外消旋化，得到外消旋体，适合进一步拆分。为了获得高产率的外消旋化条件，对不期望的（S）-3和（S）-2外消旋化的方法进行了广泛的研究。（S）-3和（S）-2也被提议。
• A convenient formation of aporphine core via benzyne chemistry: conformational analysis and synthesis of (R)-aporphine
  作者：Givago P. Perecim、Alessandro Rodrigues、Cristiano Raminelli

  DOI：10.1016/j.tetlet.2015.10.083

  日期：2015.12

  Total synthesis of (R)-aporphine has been accomplished by an approach that employs in the key step a sequence of transformations involving a [4+2] cycloaddition reaction followed by a hydrogen migration, leading to aporphine core in good yield, which was subjected to a 1D gradient NOE experiment, conformational analysis, and simple transformations, including a small scale resolution process, to afford enantiomericallyenriched aporphine alkaloid. (C) 2015 Elsevier Ltd. All rights reserved.
• 11-Substituted (<i>R</i>)-Aporphines:  Synthesis, Pharmacology, and Modeling of D_2A and 5-HT_1A Receptor Interactions
  作者：Martin H. Hedberg、Tero Linnanen、Johanna M. Jansen、Gunnar Nordvall、Stephan Hjorth、Lena Unelius、Anette M. Johansson

  DOI：10.1021/jm960189i

  日期：1996.1.1

  A series of C11-substituted (R)-aporphines and C11-oxygenated (R)-noraporphines has been synthesized and evaluated for central serotonergic and dopaminergic effects in vitro and in vivo. The various C11-substituents were introduced using efficient nickel- and palladium-catalyzed reactions of the corresponding triflate (R)-11-[[(trifluoromethyl)sulfonyl]oxy] aporphine (6), Several compounds display high affinity to serotonin 5-HT1A receptors in spite of major differences in steric bulk and electronic properties of the various C11-substituents. A change of the N-methyl group of the nonselective 3 to H [23, (R)-11-hydroxynoraporphine] or propyl [2, (R)-11-hydroxy-N-propylnoraporphine] increases the selectivity for 5-HT1A receptors (100-fold) and dopamine D-2A receptors (3-fold), respectively. Compounds 3 and 23 have similar affinities to 5-HT1A receptors, whereas the propyl substituent of 2 not only enhances the selectivity for D-2A receptors but also increases the D-2A affinity. Modeling of ligand-receptor binding site interactions yielded an interaction site model for the 5-HT1A receptor that describes a gradual change in binding mode for C11-hydroxy, -methoxy-, and -phenyl-substituted derivatives. Hydrogen bonding is hereby gradually replaced by van der Waals interactions involving a relatively large lipophilic pocket. The derived D-2A receptor model can accommodate both the N-propyl substituent of 2 and the C11-ethyl substituent of 11 [(R)-11-ethylaporphine].