(1R)-2-trimethylsilyloxy-9-azabicyclo[4.2.1]non-2-ene-9-carboxylic acid ethyl ester | 281650-61-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: (1R)-2-trimethylsilyloxy-9-azabicyclo[4.2.1]non-2-ene-9-carboxylic acid ethyl ester
• 英文别名: ethyl (1R,6R)-2-trimethylsilyloxy-9-azabicyclo[4.2.1]non-2-ene-9-carboxylate
• CAS: 281650-61-1
• 化学式: C₁₄H₂₅NO₃Si
• 分子量: 283.443
• InChiKey: DINSXXCAAPPFCK-VXGBXAGGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.51
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.79
• 拓扑面积：
  38.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (1R)-2-trimethylsilyloxy-9-azabicyclo[4.2.1]non-2-ene-9-carboxylic acid ethyl ester 在 双(三甲基硅烷基)氨基钾 、 三氟乙酸 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 7.0h， 生成 (+)-(1R)-2-(trifluoromethanesulfonyloxy)-9-azabicyclo[4.2.1]non-2-ene-9-carboxylic acid ethyl ester
  参考文献：
  名称：

  A new and efficient synthetic route to enantiopure (+)-anatoxin-a from (−)-cocaine hydrochloride

  摘要：

  The potent nAChR agonist (+)-anatoxin-a was efficiently synthesized in enantiomerically pure form starting from a readily available confiscated grade (-)-cocaine hydrochloride. The eight-step synthesis providing novel extensions to existing methodology proceeded with 26% overall yield and with stereochemical integrity of the relevant original stereogenic centers. Key steps were an effective ring expansion of the (+)-2-tropinone 2 to the 9-azabicyclo[4.2.1]nonanone 5 with TMSCHN2/Al(CH3)(3) and the introduction of the required methyl ketone side chain in masked form by reacting the corresponding enol triflate 6 with ethyl vinyl ether/Pd(OAc2) under Heck reaction conditions. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0957-4166(00)00059-8
• 作为产物：
  描述：

  (5S)-8-methyl-8-azabicyclo[3.2.1]octan-2-one 在 三甲基铝 、 potassium carbonate 作用下， 生成 (1R)-2-trimethylsilyloxy-9-azabicyclo[4.2.1]non-2-ene-9-carboxylic acid ethyl ester
  参考文献：
  名称：

  合成和评估作为新的nAChR配体的含（+/-）-吡啶并[3.4-b]高托烷和吡啶-[3.4-b]托烷的吡嗪和嘧啶的生物等排体。

  摘要：

  用哒嗪和嘧啶核生物置换（+/-）-吡啶并[3.4-b]高托烷（PHT）和吡啶[3.4-b]托烷中的吡啶药效成分导致迄今未知的nAChR配体，如5-8。逆型Diels-Alder反应构成了通往哒嗪或嘧啶环化的生物等位基因新路线的关键步骤。来自“手性库”的对映体纯（+）-2-托宁酮（11）被转化为扩环的甲硅烷基烯醇醚12和烯胺15。两者均被证明是逆型[4 + 2与1,2,4,5-四嗪13和16a，b或与1,3,5-三嗪19的环加成反应以提供对映纯的目标化合物5-7。以相同的方式从3-对pan酮21获得外消旋嘧啶环化的物质8。测试了新的配体在体外对（alpha4）2（beta2）3和alpha7 * nAChR亚型的亲和力。与众所周知对大鼠脑中激动剂结合位点表现出亲和力的PHT（约）（+）-毒素（a）相比，生物等位哒嗪取代吡啶导致的亲和力降低30倍。 （alpha4）2（beta2）3亚型。除了

  DOI：

  10.1016/s0968-0896(01)00258-9

文献信息

• Syntheses and evaluation of pyridazine and pyrimidine Containing bioisosteres of (±)-Pyrido[3.4-b]homotropane and Pyrido-[3.4-b]tropane as novel nAChR ligands
  作者：Daniela Gündisch、Thomas Kämpchen、Simone Schwarz、Gunther Seitz、Johanna Siegl、Thomas Wegge

  DOI：10.1016/s0968-0896(01)00258-9

  日期：2002.1

  (+)-anatoxin-a (1), replacement of the pyridine by the bioisosteric pyridazine resulted in 30-fold lower affinity at the (alpha4)2(beta2)3 subtype. The annulated diazinotropanes 6-8, ligands with ferruginine-like structures more or less retained the affinity of (-)-norferruginine (3) except of compound 7. Remarkably, all of the novel ligands are devoid of affinity at the alpha7* subtype.

  用哒嗪和嘧啶核生物置换（+/-）-吡啶并[3.4-b]高托烷（PHT）和吡啶[3.4-b]托烷中的吡啶药效成分导致迄今未知的nAChR配体，如5-8。逆型Diels-Alder反应构成了通往哒嗪或嘧啶环化的生物等位基因新路线的关键步骤。来自“手性库”的对映体纯（+）-2-托宁酮（11）被转化为扩环的甲硅烷基烯醇醚12和烯胺15。两者均被证明是逆型[4 + 2与1,2,4,5-四嗪13和16a，b或与1,3,5-三嗪19的环加成反应以提供对映纯的目标化合物5-7。以相同的方式从3-对pan酮21获得外消旋嘧啶环化的物质8。测试了新的配体在体外对（alpha4）2（beta2）3和alpha7 * nAChR亚型的亲和力。与众所周知对大鼠脑中激动剂结合位点表现出亲和力的PHT（约）（+）-毒素（a）相比，生物等位哒嗪取代吡啶导致的亲和力降低30倍。 （alpha4）2（beta2）3亚型。除了
• A new and efficient synthetic route to enantiopure (+)-anatoxin-a from (−)-cocaine hydrochloride
  作者：Thomas Wegge、Simone Schwarz、Gunther Seitz

  DOI：10.1016/s0957-4166(00)00059-8

  日期：2000.4

  The potent nAChR agonist (+)-anatoxin-a was efficiently synthesized in enantiomerically pure form starting from a readily available confiscated grade (-)-cocaine hydrochloride. The eight-step synthesis providing novel extensions to existing methodology proceeded with 26% overall yield and with stereochemical integrity of the relevant original stereogenic centers. Key steps were an effective ring expansion of the (+)-2-tropinone 2 to the 9-azabicyclo[4.2.1]nonanone 5 with TMSCHN2/Al(CH3)(3) and the introduction of the required methyl ketone side chain in masked form by reacting the corresponding enol triflate 6 with ethyl vinyl ether/Pd(OAc2) under Heck reaction conditions. (C) 2000 Elsevier Science Ltd. All rights reserved.