1-[2-(3,4-dimethoxyphenyl)-ethyl]-6,7-dimethoxy-3,4-dihydroisoquinoline | 20944-14-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氢异喹啉
• 英文名称: 1-[2-(3,4-dimethoxyphenyl)-ethyl]-6,7-dimethoxy-3,4-dihydroisoquinoline
• 英文别名: 6,7-dimethoxy-1-(3,4-dimethoxyphenethyl)-3,4-dihydroisoquinoline；1-(3,4-dimethoxy-phenethyl)-6,7-dimethoxy-3,4-dihydro-isoquinoline；1-(3,4-Dimethoxy-phenaethyl)-6,7-dimethoxy-3,4-dihydro-isochinolin；1-[2-(3,4-Dimethoxyphenyl)ethyl]-6,7-dimethoxy-3,4-dihydroisoquinoline
• CAS: 20944-14-3
• 化学式: C₂₁H₂₅NO₄
• 分子量: 355.434
• InChiKey: HMBAIFXFCAVTSP-UHFFFAOYSA-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：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  49.3
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-[2-(3,4-dimethoxyphenyl)-ethyl]-6,7-dimethoxy-3,4-dihydroisoquinoline 在 Noyori's catalyst 、 sodium formate 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 生成 (S)-(-)-Norhomolaudanosine
  参考文献：
  名称：

  仿生总生物碱。

  摘要：

  使用仿生方法，由花椒苷酰胺原生物碱实现了Dysoxylum生物碱的五步全合成。该合成具有直接酰胺化和Bischler-Napieralski反应形成二氢异喹啉环的特征，然后将其进行Noyori不对称转移氢化，以在C-1处建立立体异构中心。我们的合成序列为Dysoxylum生物碱的生物合成起源提供了重要的视角，因为获得了6种天然生物碱和12种合成类似物，具有很高的对映选择性，总收率高达68％。此外，我们描述了Dysoxylum生物碱对斑马鱼胚胎的急性毒性，将它们的毒性与相应的zanthoxylamide原生物碱的毒性进行了比较，并建立了对映选择性-毒性关系。

  DOI：

  10.1021/acs.joc.9b02093
• 作为产物：
  描述：

  3,4-二甲氧基苯丙酸 在 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 、 三氯氧磷 作用下， 以 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 2.0h， 生成 1-[2-(3,4-dimethoxyphenyl)-ethyl]-6,7-dimethoxy-3,4-dihydroisoquinoline
  参考文献：
  名称：

  Effect of 1-Substitution on Tetrahydroisoquinolines as Selective Antagonists for the Orexin-1 Receptor

  摘要：

  Selective blockade of the orexin-1 receptor (OX1) has been suggested as a potential approach to drug addiction therapy because of its role in modulating the brain's reward system. We have recently reported a series of tetrahydroisoquinoline-based OX1 selective antagonists. Aimed at elucidating structure-activity relationship requirements in other regions of the molecule and further enhancing OX1 potency and selectivity, we have designed and synthesized a series of analogues bearing a variety of substituents at the 1-position of the tetrahydroisoquinoline. The results show that an optimally substituted benzyl group is required for activity at the OX1 receptor. Several compounds with improved potency and/or selectivity have been identified. When combined with structural modifications that were previously found to improve selectivity, we have identified compound 73 (RTIOX-251) with an apparent dissociation constant (K-e) of 16.1 nM at the OX1 receptor and >620-fold selectivity over the OX2 receptor. In vivo, compound 73 was shown to block the development of locomotor sensitization to cocaine in rats.

  DOI：

  10.1021/cn500330v

文献信息

• Stenlake; Waigh; Dewar, European Journal of Medicinal Chemistry, 1981, vol. 16, # 6, p. 515 - 524
  作者：Stenlake、Waigh、Dewar、et al.

  DOI：——

  日期：——
• Synthesis and Radioligand Binding Studies of Methoxylated 1,2,3,4-Tetrahydroisoquinolinium Derivatives as Ligands of the Apamin-Sensitive Ca²⁺-Activated K⁺ Channels
  作者：Amaury Graulich、Jacqueline Scuvée-Moreau、Livia Alleva、Cédric Lamy、Olivier Waroux、Vincent Seutin、Jean-François Liégeois

  DOI：10.1021/jm0607395

  日期：2006.11.30

  Several methoxylated 1,2,3,4-tetrahydroisoquinoliniums derived from N-methyl-laudanosine and N-methyl-noscapine were synthesized and evaluated for their affinity for apamin-sensitive binding sites. The quaternary ammonium derivatives have a higher affinity with regard to the tertiary amines. 6,7-Dimethoxy analogues possess a higher affinity than the 6,8- and 7,8- dimethoxy isomers. A 3,4-dimethoxybenzyl or a 2-naphthylmethyl moiety in C-1 position are more favorable than a 3,4-dimethoxyphenethyl group. Smaller groups such as propyl or isobutyl are unfavorable. In 6,7-dimethoxy analogues, increasing the size and lipophilicity with a naphthyl group in the C-1 position leads to a slight increase of affinity, while the same group in the 6,7,8- trimethoxy series is less favorable. The 6,7,8- trimethoxy derivative 3f is the first tertiary amine in the series to possess an affinity close to that of N-methyl-laudanosine and N-methyl-noscapine. Moreover, electrophysiological studies show that the most effective compound 4f blocks the apamin-sensitive afterhyperpolarization in rat dopaminergic neurons.
• 375. The synthesis of dl-homolaudanosoline and its dehydrogenation
  作者：Shigehiko Sugasawa、Haruo Yoshikawa

  DOI：10.1039/jr9330001583

  日期：——
• Narang et al., Journal of the Chemical Society, 1932, p. 2510,2511
  作者：Narang et al.

  DOI：——

  日期：——
• Asymmetric Synthesis of (S)-Norlaudanosine and (S)-Tetrahydrohomopapaverine by Catalytic Asymmetric Hydrogenation with Chiral Diphosphine-Iridium(I)-Phthalimide Complex Catalysts
  作者：Toshiaki Morimoto、Naoaki Suzuki、Kazuo Achiwa

  DOI：10.3987/com-96-7635

  日期：——

  Optically active 1,2,3,4-tetrahydroisoquinoline alkaloids, (S)-norlaudanosine and (S)-tetrahydrohomopapaverine, were prepared by catalytic asymmetric hydrogenation of 1-substituted 3,4-dihydro-6,7-dimethoxyisoquinolines with 1 mol % of an iridium(I) complex of (2S,4S)-BCPM or (S)-BINAP in the presence of a phthalimide. Enantioselectivities of up to 88% ee were attained.