methyl 4(E)-ethylidene-2-(2-hydroxyethyl)-1,2,3,4,5,6-hexahydro-1,5-methanoazocino<3,4-b>indole-6β-carboxylate | 119219-81-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: methyl 4(E)-ethylidene-2-(2-hydroxyethyl)-1,2,3,4,5,6-hexahydro-1,5-methanoazocino<3,4-b>indole-6β-carboxylate
• 英文别名: methyl (1RS,5SR,6RS)-4-(E)-ethylidene-2-(2-hydroxyethyl)-1,2,3,4,5,6-hexahydro-1,5-methanoazocino<3.4-b>indole-6-carboxylate；methyl (1R,11R,12S,13E)-13-ethylidene-15-(2-hydroxyethyl)-3,15-diazatetracyclo[10.3.1.02,10.04,9]hexadeca-2(10),4,6,8-tetraene-11-carboxylate
• CAS: 119219-81-7
• 化学式: C₂₀H₂₄N₂O₃
• 分子量: 340.422
• InChiKey: QOAJCANSDKZAMJ-QJTKBDRBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  65.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl 4(E)-ethylidene-2-(2-hydroxyethyl)-1,2,3,4,5,6-hexahydro-1,5-methanoazocino<3,4-b>indole-6β-carboxylate 在 甲基磺酰氯 、 三乙胺 、 间氯过氧苯甲酸 、 三氟乙酸 、 lithium diisopropyl amide 作用下， 以 甲苯 为溶剂， 反应 8.75h， 生成 dimethyl (1S,11S,12R,13E)-13-ethylidene-15-(2,2,2-trifluoroacetyl)-3,15-diazatetracyclo[10.3.1.02,10.04,9]hexadeca-2(10),4,6,8-tetraene-3,11-dicarboxylate
  参考文献：
  名称：

  Synthetic Efforts toward Akuammiline Alkaloids from Tetracyclic 6,7-Seco Derivatives

  摘要：

  The addition of enolates derived from indole-3-acetic esters 1-3 to pyridinium salts 4, 23, and 24, followed by acid cyclization of the resulting 1,4-dihydropyridines, leads to tetrahydro-1,5-methanoazocino[3,4-b]indoles 5-7, 25-27, which have been subsequently elaborated into 4E-ethylidene(or 4 alpha-ethyl)-hexahydro-1,5-methanoazocino[3,4-b]indoles. Closure of the six-membered C ring of akuammiline alkaloids by formation of C-6/C-7 bond from appropriately N-(b)-substituted derivatives of these tetracyclic ABDE substructures has been extensively investigated. In the N-unsubstituted indole series, both cyclization of thionium ions generated either by Pummerer reaction from sulfoxide 16 or by DMTSF treatment of dithioacetal 36 and photocyclization of chloroacetamide 47 occur upon the indole nitrogen to give pentacycles 18, 38, and 49, respectively. When the indole nitrogen is blocked by a substituent, the thionium ions derived from sulfoxides 17 and 43 and dithioacetals 37 and 44 do not cyclize and lead to different products depending on the reaction conditions, whereas chloroacetamides 48 and 51 undergo a reductive photodehalogenation. Attempted radical cyclization of seleno derivatives 53, 55, and 56 under a variety of conditions gives the corresponding reduced products. Finally, attempted photoisomerization of 1-acylindole 62 leads to the N-(b)-methyl tetracycle 63.

  DOI：

  10.1021/jo951456f
• 作为产物：
  描述：

  甲基吲哚-3-乙酸盐 在 盐酸 、 sodium hydride 、 lithium diisopropyl amide 作用下， 以 苯 为溶剂， 反应 6.5h， 生成 methyl 4(E)-ethylidene-2-(2-hydroxyethyl)-1,2,3,4,5,6-hexahydro-1,5-methanoazocino<3,4-b>indole-6β-carboxylate
  参考文献：
  名称：

  Synthetic Efforts toward Akuammiline Alkaloids from Tetracyclic 6,7-Seco Derivatives

  摘要：

  The addition of enolates derived from indole-3-acetic esters 1-3 to pyridinium salts 4, 23, and 24, followed by acid cyclization of the resulting 1,4-dihydropyridines, leads to tetrahydro-1,5-methanoazocino[3,4-b]indoles 5-7, 25-27, which have been subsequently elaborated into 4E-ethylidene(or 4 alpha-ethyl)-hexahydro-1,5-methanoazocino[3,4-b]indoles. Closure of the six-membered C ring of akuammiline alkaloids by formation of C-6/C-7 bond from appropriately N-(b)-substituted derivatives of these tetracyclic ABDE substructures has been extensively investigated. In the N-unsubstituted indole series, both cyclization of thionium ions generated either by Pummerer reaction from sulfoxide 16 or by DMTSF treatment of dithioacetal 36 and photocyclization of chloroacetamide 47 occur upon the indole nitrogen to give pentacycles 18, 38, and 49, respectively. When the indole nitrogen is blocked by a substituent, the thionium ions derived from sulfoxides 17 and 43 and dithioacetals 37 and 44 do not cyclize and lead to different products depending on the reaction conditions, whereas chloroacetamides 48 and 51 undergo a reductive photodehalogenation. Attempted radical cyclization of seleno derivatives 53, 55, and 56 under a variety of conditions gives the corresponding reduced products. Finally, attempted photoisomerization of 1-acylindole 62 leads to the N-(b)-methyl tetracycle 63.

  DOI：

  10.1021/jo951456f

文献信息

• Studies on the synthesis of akuammiline-type alkaloids. Construction of the hexahydro-1,5-methanoazocino[3,4-b)indole fragment
  作者：M.-Lluïsa Bennasar、Ester Zulaica、Manel López、Joan Bosch

  DOI：10.1016/s0040-4039(00)86060-8

  日期：1988.1

  A three step route to the title tetracyclic substructure of akuammiline-type alkaloids consisting in the nucleophilic addition of an ester α-anion to an N-alkylpyridinium salt, acid-induced cyclization of the resultant 1,4-dihydropyridine, and stereoselective elaboration of the ethylidene substituent is reported.

  标题为akuammiline型生物碱的四环亚结构的三步路线，包括将酯α-阴离子亲核加成至N-烷基吡啶鎓盐，酸诱导所得1,4-二氢吡啶的环化反应以及立体选择报道了亚乙基取代基。
• General method for the synthesis of bridged indole alkaloids. Nucleophilic addition of indoleacetic ester enolates to N-alkylpyridinium salts
  作者：M. Lluisa Bennasar、Mercedes Alvarez、Rodolfo Lavilla、Ester Zulaica、Joan Bosch

  DOI：10.1021/jo00291a013

  日期：1990.2
• Synthetic Efforts toward Akuammiline Alkaloids from Tetracyclic 6,7-Seco Derivatives
  作者：M.-Lluïsa Bennasar、Ester Zulaica、Antonio Ramírez、Joan Bosch

  DOI：10.1021/jo951456f

  日期：1996.1.1

  The addition of enolates derived from indole-3-acetic esters 1-3 to pyridinium salts 4, 23, and 24, followed by acid cyclization of the resulting 1,4-dihydropyridines, leads to tetrahydro-1,5-methanoazocino[3,4-b]indoles 5-7, 25-27, which have been subsequently elaborated into 4E-ethylidene(or 4 alpha-ethyl)-hexahydro-1,5-methanoazocino[3,4-b]indoles. Closure of the six-membered C ring of akuammiline alkaloids by formation of C-6/C-7 bond from appropriately N-(b)-substituted derivatives of these tetracyclic ABDE substructures has been extensively investigated. In the N-unsubstituted indole series, both cyclization of thionium ions generated either by Pummerer reaction from sulfoxide 16 or by DMTSF treatment of dithioacetal 36 and photocyclization of chloroacetamide 47 occur upon the indole nitrogen to give pentacycles 18, 38, and 49, respectively. When the indole nitrogen is blocked by a substituent, the thionium ions derived from sulfoxides 17 and 43 and dithioacetals 37 and 44 do not cyclize and lead to different products depending on the reaction conditions, whereas chloroacetamides 48 and 51 undergo a reductive photodehalogenation. Attempted radical cyclization of seleno derivatives 53, 55, and 56 under a variety of conditions gives the corresponding reduced products. Finally, attempted photoisomerization of 1-acylindole 62 leads to the N-(b)-methyl tetracycle 63.