methyl (2R,7aR,12aR,13R,E)-3-ethylidene-13-hydroxy-1,2,3,4,6,7-hexahydro-12H-7a,2-ethanoindolizino[8a,1-b]indole-12-carboxylate | 863312-54-3

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 马钱子生物碱
• 英文名称: methyl (2R,7aR,12aR,13R,E)-3-ethylidene-13-hydroxy-1,2,3,4,6,7-hexahydro-12H-7a,2-ethanoindolizino[8a,1-b]indole-12-carboxylate
• CAS: 863312-54-3
• 化学式: C₂₀H₂₄N₂O₃
• 分子量: 340.422
• InChiKey: PEYFUYPAQQVQRX-HCDBXXOTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.64
• 重原子数：
  25.0
• 可旋转键数：
  0.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  53.01
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  methyl (2R,7aR,12aR,13R,E)-3-ethylidene-13-hydroxy-1,2,3,4,6,7-hexahydro-12H-7a,2-ethanoindolizino[8a,1-b]indole-12-carboxylate 在 戴斯-马丁氧化剂 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 生成 dimethyl (1R,9R,11S,12E)-12-ethylidene-17-hydroxy-8,14-diazapentacyclo[9.5.2.01,9.02,7.09,14]octadeca-2,4,6,17-tetraene-8,18-dicarboxylate
  参考文献：
  名称：

  Sequential Catalytic Asymmetric Heck−Iminium Ion Cyclization:  Enantioselective Total Synthesis of the Strychnos Alkaloid Minfiensine

  摘要：

  A catalytic asymmetric method for the chemical synthesis of alkaloids containing the 1,2,3,4-tetrahydro-9a,4a-(iminoethano)-9H-carbazole (1) moiety is reported and verified by the enantioselective total synthesis of (+)-minfiensine (4). The central step in this total synthesis is the sequential catalytic asymmetric Heck-N-acyliminium ion cyclization of dienyl carbamate triflate 10, prepared in six steps from 1,2-cyclohexanedione, to give enantiopure 3,4-dihydro-9a,4a-(iminoethano)-9H-carbazole (12) in 75% yield. Iminoethano-9H-carbazole 12 is transformed in six steps to dienyl iodide 17, which undergoes diastereoselective intramolecular Heck cyclization to form pentacyclic intermediate 18. In eight additional steps, this latter intermediate is transformed to (+)-minfiensine (4).

  DOI：

  10.1021/ja0533895
• 作为产物：
  描述：

  8-O-methyl 16-O-prop-2-enyl (1R,9R,13R)-13-triethylsilyloxy-8,16-diazatetracyclo[7.4.3.01,9.02,7]hexadeca-2,4,6,11-tetraene-8,16-dicarboxylate 在 palladium diacetate 四氢吡咯 、 四(三苯基膦)钯 、 四丁基氟化铵 、 四丁基氯化铵 、 sodium formate 、 potassium carbonate 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 1.5h， 生成 methyl (2R,7aR,12aR,13R,E)-3-ethylidene-13-hydroxy-1,2,3,4,6,7-hexahydro-12H-7a,2-ethanoindolizino[8a,1-b]indole-12-carboxylate
  参考文献：
  名称：

  Sequential Catalytic Asymmetric Heck−Iminium Ion Cyclization:  Enantioselective Total Synthesis of the Strychnos Alkaloid Minfiensine

  摘要：

  A catalytic asymmetric method for the chemical synthesis of alkaloids containing the 1,2,3,4-tetrahydro-9a,4a-(iminoethano)-9H-carbazole (1) moiety is reported and verified by the enantioselective total synthesis of (+)-minfiensine (4). The central step in this total synthesis is the sequential catalytic asymmetric Heck-N-acyliminium ion cyclization of dienyl carbamate triflate 10, prepared in six steps from 1,2-cyclohexanedione, to give enantiopure 3,4-dihydro-9a,4a-(iminoethano)-9H-carbazole (12) in 75% yield. Iminoethano-9H-carbazole 12 is transformed in six steps to dienyl iodide 17, which undergoes diastereoselective intramolecular Heck cyclization to form pentacyclic intermediate 18. In eight additional steps, this latter intermediate is transformed to (+)-minfiensine (4).

  DOI：

  10.1021/ja0533895

文献信息

• Total Synthesis of the Strychnos Alkaloid (+)-Minfiensine: Tandem Enantioselective Intramolecular Heck−Iminium Ion Cyclization
  作者：Amy B. Dounay、Philip G. Humphreys、Larry E. Overman、Aaron D. Wrobleski

  DOI：10.1021/ja800163v

  日期：2008.4.1

  more concise total synthesis, an intramolecular palladium-catalyzed ketone enolate vinyl iodide coupling was employed to construct the final ring of (+)-minfiensine. This second-generation total synthesis of enantiopure (+)-minfiensine was accomplished in 6.5% overall yield and 15 steps from 1,2-cyclohexanedione and anisidine 13. A distinctive feature of this sequence is the use of palladium-catalyzed

  A 1,2,3,4-四氢-9a,4a-(亚氨基乙醇)-9H-咔唑 (4) 是马钱子生物碱 minfiensine (1) 和 akuammiline 生物碱如长春花碱 (5) 和乙胺嘧啶 ( 6). 开发了级联催化不对称 Heck-iminium 环化，可快速提供高对映体纯度的 3,4-二氢-9a,4a-(亚氨基乙醇)-9H-咔唑。开发了两个序列用于将 3,4-dihydro-9a,4a-(iminoethano)-9H-carbazole 27 推进到 (+)-minfiensine。在我们的第一代方法中，采用还原性 Heck 环化来形成 (+)-minfiensine 的第五个环。在第二个更简洁的全合成中，采用分子内钯催化的酮烯醇乙烯基碘偶联来构建 (+)-minfiensine 的最终环。