tert-butyl 1-(4-hydroxybenzyl)-6,7-dimethoxy-3,4-dihydroisoquinoline-2(1H)-carboxylate | 1609169-60-9

• 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: tert-butyl 1-(4-hydroxybenzyl)-6,7-dimethoxy-3,4-dihydroisoquinoline-2(1H)-carboxylate
• CAS: 1609169-60-9
• 化学式: C₂₃H₂₉NO₅
• 分子量: 399.487
• InChiKey: MIQFTFCPOBKZHI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.49
• 重原子数：
  29.0
• 可旋转键数：
  4.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  68.23
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  tert-butyl 1-(4-hydroxybenzyl)-6,7-dimethoxy-3,4-dihydroisoquinoline-2(1H)-carboxylate 在 碳酸氢钠 、 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 、 丁酮 为溶剂， 反应 30.0h， 生成 tert-butyl 6,7-dimethoxy-1-(4-((6-(2-methylpyrrolidin-1-yl)hexyl)oxy)benzyl)-3,4-dihydroisoquinoline-2(1H)-carboxylate
  参考文献：
  名称：

  Design, synthesis and biological evaluation of benzylisoquinoline derivatives as multifunctional agents against Alzheimer’s disease

  摘要：

  A novel series of benzylisoquinoline derivatives were designed, synthesized, and evaluated as multifunctional agents against Alzheimer's disease (AD). The screening results showed that most of the compounds significantly inhibited cholinesterases (ChEs), human cholinesterases (h-ChEs) and self-induced beta-amyloid (A beta) aggregation. In particular, compound 9k showed the strongest acetylcholinesterase (AChE) inhibitory activity, being 1000-fold and 3-fold more potent than its precursor benzylisoquinoline (10) and the positive control galanthamine, respectively. In addition, 9k was a moderately potent inhibitor for h-ChEs. Compared with precursor benzylisoquinoline (36.0% at 20 mu M), 9k (78.4% at 20 mu M) could further inhibit Ab aggregation. Moreover, 9k showed low cell toxicity in human SH-SY5Y neuroblastoma cells. Therefore, compound 9k might be a promising lead compound for AD treatment. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.03.058
• 作为产物：
  描述：

  N-(2-(3,4-dimethoxyphenyl)ethyl)-2-(4-hydroxyphenyl)acetamide 在 sodium tetrahydroborate 、 palladium 10% on activated carbon 、 氢气 、 potassium carbonate 、 三氯氧磷 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 、 甲苯 为溶剂， 反应 72.0h， 生成 tert-butyl 1-(4-hydroxybenzyl)-6,7-dimethoxy-3,4-dihydroisoquinoline-2(1H)-carboxylate
  参考文献：
  名称：

  Design, synthesis and biological evaluation of benzylisoquinoline derivatives as multifunctional agents against Alzheimer’s disease

  摘要：

  A novel series of benzylisoquinoline derivatives were designed, synthesized, and evaluated as multifunctional agents against Alzheimer's disease (AD). The screening results showed that most of the compounds significantly inhibited cholinesterases (ChEs), human cholinesterases (h-ChEs) and self-induced beta-amyloid (A beta) aggregation. In particular, compound 9k showed the strongest acetylcholinesterase (AChE) inhibitory activity, being 1000-fold and 3-fold more potent than its precursor benzylisoquinoline (10) and the positive control galanthamine, respectively. In addition, 9k was a moderately potent inhibitor for h-ChEs. Compared with precursor benzylisoquinoline (36.0% at 20 mu M), 9k (78.4% at 20 mu M) could further inhibit Ab aggregation. Moreover, 9k showed low cell toxicity in human SH-SY5Y neuroblastoma cells. Therefore, compound 9k might be a promising lead compound for AD treatment. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.03.058

文献信息

• A para- to meta-isomerization of phenols
  作者：Simon Edelmann、Jean-Philip Lumb

  DOI：10.1038/s41557-024-01512-1

  日期：2024.7

  Their properties are intimately linked to the relative substitution pattern of the aromatic ring, reflecting well-known electronic effects of the OH group. Because of these ortho-, para-directing effects, meta-substituted phenols have historically been more difficult to synthesize. Here we describe a procedure to transpose phenols that hinges on a regioselective diazotization of the corresponding ortho-quinone

  酚类及其衍生物在自然界中无处不在，是至关重要的工业化学品。它们的性质与芳香环的相对取代模式密切相关，反映了 OH 基团众所周知的电子效应。由于这些邻位、旁向效应，间位取代酚类在历史上更难合成。在这里，我们描述了一种转置酚类的程序，该程序取决于相应邻醌的区域选择性重氮化。该程序直接从其更常见和可获得的对位取代异构体中获得间位取代苯酚，并表现出良好的化学选择性，使其能够在后期环境中应用。通过改变 OH 基团的电子效应及其氢键轨迹，我们的转座可用于使天然产物和现有化学库多样化，并可能缩短生产代表性不足的芳烃异构体的时间和成本。