(1S)-6-methoxy-1-[(3-methoxy-4-phenylmethoxyphenyl)methyl]-7-phenylmethoxy-1,2,3,4-tetrahydroisoquinoline | 1361089-32-8

• 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: (1S)-6-methoxy-1-[(3-methoxy-4-phenylmethoxyphenyl)methyl]-7-phenylmethoxy-1,2,3,4-tetrahydroisoquinoline
• CAS: 1361089-32-8
• 化学式: C₃₂H₃₃NO₄
• 分子量: 495.618
• InChiKey: KKZIPSQZTJEWBP-NDEPHWFRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.2
• 重原子数：
  37
• 可旋转键数：
  10
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  49
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (1S)-6-methoxy-1-[(3-methoxy-4-phenylmethoxyphenyl)methyl]-7-phenylmethoxy-1,2,3,4-tetrahydroisoquinoline 在 盐酸 作用下， 以 甲醇 、 乙醚 为溶剂， 以85%的产率得到(1S)-6-methoxy-1-[(3-methoxy-4-phenylmethoxyphenyl)methyl]-7-phenylmethoxy-1,2,3,4-tetrahydroisoquinoline;hydrochloride
  参考文献：
  名称：

  First enantioselective syntheses of the dopamine D1 and D2 receptor modulators, (+)- and (−)-govadine

  摘要：

  There is a pressing need to find and develop new antipsychotic agents for the treatment of schizophrenia. Current drugs primarily target dopamine D2receptors and are only effective in the treatment of the positive symptoms of this indication. The tetrahydroprotoberberine natural product (+/-)- govadine has shown unique promise for the treatment of both the positive and negative symptoms of schizophrenia as it targets both dopamine D1 and D2 receptors. However, further clinical research has been hindered by the lack of availability of significant quantities of enantioenriched material. A new, enantioselective synthetic route has been developed that affords (-)- govadine in 39% overall yield over 5-steps from commercially available dopamine and homovanillic acid derivatives. Using only minor modifications in the synthetic route, (+)-govadine can be synthesized in comparable yields and enantioselectivities. The route is readily scalable as every intermediate was purified by crystallization and no flash column chromatography was necessary. (C) 2012 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2012.01.005
• 作为产物：
  描述：

  (4-benzyloxy-3-methoxy-phenyl)-acetic acid-(4-benzyloxy-3-methoxy-phenethylamide) 在 甲酸 、 (S,S)-N-(对甲苯磺酰)-1,2-二苯乙烷二胺(对异丙基苯)氯化钌(II) 、 三乙胺 、 三氯氧磷 作用下， 以 N,N-二甲基甲酰胺 、 苯 为溶剂， 生成 (1S)-6-methoxy-1-[(3-methoxy-4-phenylmethoxyphenyl)methyl]-7-phenylmethoxy-1,2,3,4-tetrahydroisoquinoline
  参考文献：
  名称：

  First enantioselective syntheses of the dopamine D1 and D2 receptor modulators, (+)- and (−)-govadine

  摘要：

  There is a pressing need to find and develop new antipsychotic agents for the treatment of schizophrenia. Current drugs primarily target dopamine D2receptors and are only effective in the treatment of the positive symptoms of this indication. The tetrahydroprotoberberine natural product (+/-)- govadine has shown unique promise for the treatment of both the positive and negative symptoms of schizophrenia as it targets both dopamine D1 and D2 receptors. However, further clinical research has been hindered by the lack of availability of significant quantities of enantioenriched material. A new, enantioselective synthetic route has been developed that affords (-)- govadine in 39% overall yield over 5-steps from commercially available dopamine and homovanillic acid derivatives. Using only minor modifications in the synthetic route, (+)-govadine can be synthesized in comparable yields and enantioselectivities. The route is readily scalable as every intermediate was purified by crystallization and no flash column chromatography was necessary. (C) 2012 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2012.01.005

文献信息

• TETRAHYDROPROTOBERBINE COMPOUNDS AND USES THEREOF IN THE TREATMENT OF NEUROLOGICAL, PSYCHIATRIC AND NEURODEGENERATIVE DISEASES
  申请人：Miller James Jackson

  公开号：US20170100389A1

  公开（公告）日：2017-04-13

  Tetrahydroprotoberbine (THPB) compounds and their use in the treatment of neurological, psychiatric and neurodegenerative diseases is provided. The compounds include d-govadine, l-govadine and racemic govadine, as well as d-THPBs of general formula (I). Enantioselective processes for preparing compounds of formula (I), and d- and l-govadine are also provided.