(E)-11-ethylidene-5,6,9,10-tetrahydro-5-(methoxycarbonylamino)-7-methyl-5,9-methano-1H-cycloocta[b]pyridin-2-one | 134287-15-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: (E)-11-ethylidene-5,6,9,10-tetrahydro-5-(methoxycarbonylamino)-7-methyl-5,9-methano-1H-cycloocta[b]pyridin-2-one
• 英文别名: methyl N-[(13E)-13-ethylidene-11-methyl-5-oxo-6-azatricyclo[7.3.1.02,7]trideca-2(7),3,10-trien-1-yl]carbamate
• CAS: 134287-15-3
• 化学式: C₁₇H₂₀N₂O₃
• 分子量: 300.357
• InChiKey: PWALGDQWLMXUIT-UUILKARUSA-N

物化性质

• 沸点：
  578.2±50.0 °C(Predicted)
• 密度：
  1.24±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  67.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (E)-11-ethylidene-5,6,9,10-tetrahydro-5-(methoxycarbonylamino)-7-methyl-5,9-methano-1H-cycloocta[b]pyridin-2-one 在 lithium thiopropiolate 作用下， 以 六甲基磷酰三胺 为溶剂， 反应 24.0h， 以66%的产率得到(+/-)-huperzine
  参考文献：
  名称：

  rac-石杉碱甲及其rac -7-乙基衍生物的新合成。几种蛇蝎子类似物作为乙酰胆碱酯酶抑制剂的评价

  摘要：

  rac-石杉碱甲，其rac -7-乙基衍生物和两个区域异构体类似物是通过合成序列制备的，该过程涉及在后期阶段通过吡啶环烯胺中间体与丙醇酰胺的反应对吡啶酮环进行精制，从而得到区域异构体的混合物。吡啶酮衍生物。确定了这些化合物和其他两个最近描述的11个未取代的石杉碱A类似物的乙酰胆碱酯酶抑制活性，石杉碱A的rac -7-乙基类似物是活性最高的化合物，尽管其活性比（-）-低约12倍。石杉碱甲

  DOI：

  10.1016/s0040-4020(00)00363-x
• 作为产物：
  描述：

  7’,8’-dihydro-5’H-spiro[1,3-dioxolane-2,6’-quinoline]-2’-ol 在 4-二甲氨基吡啶 、 palladium diacetate 、 Wilkinson's catalyst 、 三苯基膦 盐酸 、 sodium hydroxide 、 氯化亚砜 、 sodium azide 、 偶氮二异丁腈 、 碘代三甲硅烷 、 oxonium 、 sodium acetate 、 potassium hydride 、 sodium hydride 、 三乙胺 、 silver carbonate 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 二氯甲烷 、 氯仿 、 溶剂黄146 、 丙酮 、 甲苯 为溶剂， 反应 127.0h， 生成 (E)-11-ethylidene-5,6,9,10-tetrahydro-5-(methoxycarbonylamino)-7-methyl-5,9-methano-1H-cycloocta[b]pyridin-2-one
  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

• PREPARATION OF (-)-HUPERZINE A
  申请人：ZHEJIANG WANBANG PHARMACEUTICAL PLC.

  公开号：US20160159745A1

  公开（公告）日：2016-06-09

  The present invention relates to a method for preparing (−)-huperzine A. The method involves: allowing a mixture of (±)-huperzine A obtained from chemical synthesis and a chiral acid to form (±)-huperzine A chiral acid salt under suitable conditions; recrystallizing the chiral acid salt from an organic solvent and basifying with an alkali to obtain optically pure (−)-huperzine A. The method is convenient to operate and suitable for industrial production. The chemical purity and optical purity of (−)-huperzine A obtained by the method are each greater than 99.5%, satisfying the requirement for raw pharmaceutical purity in the pharmaceutical industry.

  本发明涉及一种制备(−)-扶林辛A的方法。该方法包括：在适当条件下，使从化学合成得到的(±)-扶林辛A与手性酸的混合物形成(±)-扶林辛A手性酸盐；从有机溶剂中重新结晶化手性酸盐，并用碱性物质碱化以获得光学纯的(−)-扶林辛A。该方法操作方便，适合工业生产。该方法获得的(−)-扶林辛A的化学纯度和光学纯度均大于99.5%，满足制药行业原料药纯度要求。
• KOZIKOWSKI, ALAN P.;XIA, YAN;REDDY, E. RAJARATHNAM;TUCKMANTEL, WERNER;HAN+, J. ORG. CHEM., 56,(1991) N5, C. 4636-4645
  作者：KOZIKOWSKI, ALAN P.、XIA, YAN、REDDY, E. RAJARATHNAM、TUCKMANTEL, WERNER、HAN+

  DOI：——

  日期：——
• US9586904B2
  申请人：——

  公开号：US9586904B2

  公开（公告）日：2017-03-07
• New Syntheses of rac-Huperzine A and its rac-7-Ethyl-Derivative. Evaluation of Several Huperzine A Analogues as Acetylcholinesterase Inhibitors
  作者：Pelayo Camps、Joan Contreras、Rachid El Achab、Jordi Morral、Diego Muñoz-Torrero、Mercè Font-Bardia、Xavier Solans、Albert Badia、Nuria M Vivas

  DOI：10.1016/s0040-4020(00)00363-x

  日期：2000.6

  rac-Huperzine A, its rac-7-ethyl-derivative and two regioisomeric analogues have been prepared through synthetic sequences involving the elaboration of the pyridone ring in a late stage, by reaction of an intermediate pyrrolidine enamine with propiolamide, which gave mixtures of regioisomeric pyridone derivatives. The acetylcholinesterase inhibitory activity of these and two other recently described 11-unsubstituted

  rac-石杉碱甲，其rac -7-乙基衍生物和两个区域异构体类似物是通过合成序列制备的，该过程涉及在后期阶段通过吡啶环烯胺中间体与丙醇酰胺的反应对吡啶酮环进行精制，从而得到区域异构体的混合物。吡啶酮衍生物。确定了这些化合物和其他两个最近描述的11个未取代的石杉碱A类似物的乙酰胆碱酯酶抑制活性，石杉碱A的rac -7-乙基类似物是活性最高的化合物，尽管其活性比（-）-低约12倍。石杉碱甲
• Synthesis of huperzine A, its analogs, and their anticholinesterase activity
  作者：Alan P. Kozikowski、Yan Xia、E. Rajarathnam Reddy、Werner Tuckmantel、Israel Hanin、X. C. Tang

  DOI：10.1021/jo00015a014

  日期：1991.7

  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.