(6aR)-6-methyl-5,6,6a,7-tetrahydro-4H-dibenzo[de,g]quinolin-1,2-diol | 3175-79-9

• 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: (6aR)-6-methyl-5,6,6a,7-tetrahydro-4H-dibenzo[de,g]quinolin-1,2-diol
• 英文别名: 1,2-dihydroxyaporphine；6-methyl-6aβ-aporphane-1,2-diol；6-Methyl-6aβ-aporphan-1,2-diol；(6aR)-6-methyl-5,6,6a,7-tetrahydro-4H-dibenzo[de,g]quinoline-1,2-diol
• CAS: 3175-79-9
• 化学式: C₁₇H₁₇NO₂
• 分子量: 267.327
• InChiKey: SYKWSIUDXOQIDR-CYBMUJFWSA-N

物化性质

• 沸点：
  472.1±45.0 °C(Predicted)
• 密度：
  1.299±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  20
• 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：
  43.7
• 氢给体数：
  2
• 氢受体数：
  3

安全信息

• 海关编码：
  2933990090

反应信息

• 作为产物：
  描述：

  荷叶碱 在 sodium tetrahydroborate 、 aluminum tri-bromide 、 二苄基二硒醚 作用下， 以 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 48.0h， 生成 (6aR)-6-methyl-5,6,6a,7-tetrahydro-4H-dibenzo[de,g]quinolin-1,2-diol
  参考文献：
  名称：

  Synthesis and structure–activity relationship of nuciferine derivatives as potential acetylcholinesterase inhibitors

  摘要：

  Acetylcholinesterase inhibitors (AChEIs) are currently the best available pharmacotherapy for Alzheimer patients, but because of bioavailability issues, there is still great interest in discovering better AChEIs. The aporphine alkaloid is an important class of natural products, which shows diverse biological activity, such as acetylcholinesterase inhibitory activity. To find new lead AChEIs compounds, eight aporphine alkaloids were synthesized by O-dealkylation, N-dealkylation, and ring aromatization reactions using nuciferine as raw material. The anti-acetylcholinesterase activity of synthesized compounds was measured using modified Ellman's method. The results showed that some synthesized compounds exhibited higher affinity to AChE than the parent compound nuciferine. Among these compounds, 1,2-dihydroxyaporphine (2) and dehydronuciferine (5) were the most active compounds (IC50 = 28 and 25 mu g/mL, respectively). Preliminary analysis of structure-activity relationships suggested that aromatization of the C ring, the presence of the alkoxyl group at C1 and the hydroxy group at C2 position as well as the alkyl substituent at the N atom were favorable to the acetylcholinesterase inhibition. Molecular docking was also applied to predict the binding modes of compounds 1, 2, and 9 into the huperzine A binding site of AChE.

  DOI：

  10.1007/s00044-013-0905-9

文献信息

• Aporphines. 9. Synthesis and Pharmacological Evaluation of (±) 9, 10-Dihydroxyaporphine [(±)-Isoapomorphine], (±)-,(-)-, and (±)-1,2-Dihydroxyaporphine, and (+)-1, 2, 9, 10 - Tetrahydroxyaporphine.
  作者：John Neumeyer、Monica McCarthy、Sam Battista、Franklin Rosenberg、David Teiger

  DOI：10.1021/jm00269a602

  日期：1973.11
• Junussow; Konowalowa; Orechow, Zhurnal Obshchei Khimii, 1939, vol. 9, p. 1868,1874, 1875
  作者：Junussow、Konowalowa、Orechow

  DOI：——

  日期：——
• Synthesis and structure–activity relationship of nuciferine derivatives as potential acetylcholinesterase inhibitors
  作者：Zhongduo Yang、Zhuwen Song、Weiwei Xue、Jie Sheng、Zongmei Shu、Yin Shi、Jibei Liang、Xiaojun Yao

  DOI：10.1007/s00044-013-0905-9

  日期：2014.6

  Acetylcholinesterase inhibitors (AChEIs) are currently the best available pharmacotherapy for Alzheimer patients, but because of bioavailability issues, there is still great interest in discovering better AChEIs. The aporphine alkaloid is an important class of natural products, which shows diverse biological activity, such as acetylcholinesterase inhibitory activity. To find new lead AChEIs compounds, eight aporphine alkaloids were synthesized by O-dealkylation, N-dealkylation, and ring aromatization reactions using nuciferine as raw material. The anti-acetylcholinesterase activity of synthesized compounds was measured using modified Ellman's method. The results showed that some synthesized compounds exhibited higher affinity to AChE than the parent compound nuciferine. Among these compounds, 1,2-dihydroxyaporphine (2) and dehydronuciferine (5) were the most active compounds (IC50 = 28 and 25 mu g/mL, respectively). Preliminary analysis of structure-activity relationships suggested that aromatization of the C ring, the presence of the alkoxyl group at C1 and the hydroxy group at C2 position as well as the alkyl substituent at the N atom were favorable to the acetylcholinesterase inhibition. Molecular docking was also applied to predict the binding modes of compounds 1, 2, and 9 into the huperzine A binding site of AChE.