(E)-(+/-)-11-ethylidene-9,10-dihydro-2-methoxy-7-methyl-5,9-methanocyclooctapyridine-5(6H)-carboxylic acid methyl ester | 120786-17-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (E)-(+/-)-11-ethylidene-9,10-dihydro-2-methoxy-7-methyl-5,9-methanocyclooctapyridine-5(6H)-carboxylic acid methyl ester
• 英文别名: (E)-(+/-)-11-ethylidene-9,10-dihydro-2-methoxy-7-methyl-5,9-methanocycloocta[b]pyridine-5(6H)-carboxylic acid methyl ester；methyl (13E)-13-ethylidene-5-methoxy-11-methyl-6-azatricyclo[7.3.1.02,7]trideca-2(7),3,5,10-tetraene-1-carboxylate
• CAS: 120786-17-6
• 化学式: C₁₈H₂₁NO₃
• 分子量: 299.37
• InChiKey: HYPRSWDGWDBYQC-WLRTZDKTSA-N

物化性质

• 沸点：
  369.5±42.0 °C(Predicted)
• 密度：
  1.204±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  48.4
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (E)-(+/-)-11-ethylidene-9,10-dihydro-2-methoxy-7-methyl-5,9-methanocyclooctapyridine-5(6H)-carboxylic acid methyl ester 在 4-二甲氨基吡啶 、 18-冠醚-6 lithium aluminium tetrahydride 、 sodium azide 、 三乙胺 作用下， 以 四氢呋喃 、 六甲基磷酰三胺 、 二氯甲烷 为溶剂， 反应 22.0h， 生成 [(13E)-13-ethylidene-5-methoxy-11-methyl-6-azatricyclo[7.3.1.02,7]trideca-2(7),3,5,10-tetraen-1-yl]methanamine
  参考文献：
  名称：

  Synthesis of huperzine A, its analogs, and their anticholinesterase activity

  摘要：

  Huperzine A is a new alkaloid isolated from the club moss Huperzia serrata (Thunb.) Trev., a Chinese folk medicine. This alkaloid exhibits potent activity as an inhibitor of acetylcholinesterase. Consequently, the compound is presently being investigated in China for the treatment of individuals suffering from various forms of memory impairment including Alzheimer's dementia. Details of the total synthesis of (+/-)-huperzine A are described as well as the preparation of a variety of huperzine analogues including its presumed pharmacophore. The extent of these new compounds to inhibit acetylcholinesterase is presented along with a discussion of the effects of the structural changes on biological activity.

  DOI：

  10.1021/jo00015a014
• 作为产物：
  描述：

  1-(1,4-dioxaspiro[4.5]dec-7-en-8-yl)pyrrolidine 在 4-二甲氨基吡啶 、 palladium hydroxide - carbon 盐酸 、 偶氮二异丁腈 、 氢气 、 sodium acetate 、 potassium hydride 、 三乙胺 、 silver carbonate 、 四甲基胍 作用下， 以 二氯甲烷 、 氯仿 、 溶剂黄146 、 丙酮 为溶剂， 反应 97.0h， 生成 (E)-(+/-)-11-ethylidene-9,10-dihydro-2-methoxy-7-methyl-5,9-methanocyclooctapyridine-5(6H)-carboxylic acid methyl ester
  参考文献：
  名称：

  Synthesis of huperzine A, its analogs, and their anticholinesterase activity

  摘要：

  Huperzine A is a new alkaloid isolated from the club moss Huperzia serrata (Thunb.) Trev., a Chinese folk medicine. This alkaloid exhibits potent activity as an inhibitor of acetylcholinesterase. Consequently, the compound is presently being investigated in China for the treatment of individuals suffering from various forms of memory impairment including Alzheimer's dementia. Details of the total synthesis of (+/-)-huperzine A are described as well as the preparation of a variety of huperzine analogues including its presumed pharmacophore. The extent of these new compounds to inhibit acetylcholinesterase is presented along with a discussion of the effects of the structural changes on biological activity.

  DOI：

  10.1021/jo00015a014

文献信息

• Methods of resolving racemic mixture to obtain (−)-huperzine A
  申请人：AMPHASTAR PHARMACEUTICALS INC.

  公开号：US10287249B2

  公开（公告）日：2019-05-14

  A method of resolving a racemic mixture of (±)-Huperzine A to (−)-Huperzine A includes: separating the (−)-Huperzine A from the racemic mixture of (±)-Huperzine A by chiral high performance liquid chromatography (HPLC), the chiral HPLC being performed utilizing a mobile phase including a solution including an alcohol and one selected from dichloromethane, trichloromethane, and a mixture thereof, and the chiral HPLC being performed utilizing a chiral stationary phase including a polysaccharide derivative.

  一种将(±)-Huperzine A的外消旋混合物解析为(-)-Huperzine A的方法包括通过手性高效液相色谱法（HPLC）从(±)-Huperzine A的外消旋混合物中分离出(-)-Huperzine A，手性高效液相色谱法使用的流动相包括醇和选自二氯甲烷、三氯甲烷及其混合物的溶液，手性高效液相色谱法使用的手性固定相包括多糖衍生物。
• Methods of resolving racemic mixture to obtain (−)-Huperzine A
  申请人：AMPHASTAR NANJING PHARMACEUTICALS INC.

  公开号：US10829455B2

  公开（公告）日：2020-11-10

  A method of resolving a racemic mixture of (±)-Huperzine A to (−)-Huperzine A includes: separating the (−)-Huperzine A from the racemic mixture of (±)-Huperzine A by chiral high performance liquid chromatography (HPLC), the chiral HPLC being performed utilizing a mobile phase including a solution including an alcohol and one selected from dichloromethane, trichloromethane, and a mixture thereof, and the chiral HPLC being performed utilizing a chiral stationary phase including a polysaccharide derivative.

  一种将(±)-Huperzine A的外消旋混合物解析为(-)-Huperzine A的方法包括通过手性高效液相色谱法（HPLC）从(±)-Huperzine A的外消旋混合物中分离出(-)-Huperzine A，手性高效液相色谱法使用的流动相包括醇和选自二氯甲烷、三氯甲烷及其混合物的溶液，手性高效液相色谱法使用的手性固定相包括多糖衍生物。
• Synthetic chemistry, neurotransmission and second messengers
  作者：Alan P. Kozikowski

  DOI：10.1002/jhet.5570270108

  日期：1990.1
• A practical synthesis of the Chinese "nootropic" agent huperzine A: a possible lead in the treatment of Alzheimer's disease
  作者：Yan Xia、Alan P. Kozikowski

  DOI：10.1021/ja00193a062

  日期：1989.5
• Synthesis and biological evaluation of (±)-Z-huperzine A
  作者：Alan P. Kozikowski、Fumio Yamada、X.-C. Tang、Israel Hanin

  DOI：10.1016/s0040-4039(00)97013-8

  日期：1990.1