(+)-minfiensine

• 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: (+)-minfiensine
• 英文别名: minfiensine；[(1R,9S,11S,12E)-12-ethylidene-8,14-diazapentacyclo[9.5.2.01,9.02,7.09,14]octadeca-2,4,6,17-tetraen-18-yl]methanol
• 化学式: C₁₉H₂₂N₂O
• 分子量: 294.396
• InChiKey: HICMXDKNSCMBDU-CMAKCSRNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  22
• 可旋转键数：
  1
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  35.5
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  dimethyl (1R,9R,11S,12E)-12-ethylidene-8,14-diazapentacyclo[9.5.2.01,9.02,7.09,14]octadeca-2,4,6,17-tetraene-8,18-dicarboxylate 在 sodium hydroxide 、 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 2.5h， 生成 (+)-minfiensine
  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。
• Total Synthesis of (+)-Minfiensine: Construction of the Tetracyclic Core Structure by an Asymmetric Cascade Cyclization
  作者：Ze-Xin Zhang、Si-Cong Chen、Lei Jiao

  DOI：10.1002/anie.201602771

  日期：2016.7.4

  method for one‐step construction of the tetracyclic core structure of the indole alkaloid (+)‐minfiensine was developed utilizing a palladium‐catalyzed asymmetric indole dearomatization/iminium cyclization cascade. An efficient total synthesis of (+)‐minfiensine was realized using this strategy. The present method enables access to the common core structure of a series of monoterpene indole alkaloids, such

  利用钯催化的不对称吲哚脱芳香化/亚胺环化级联反应，开发了一种一步法构建吲哚生物碱（+）-非芬太尼四环核结构的新方法。使用该策略可以有效地合成（+）-minfiensine。本方法使得能够获得一系列单萜吲哚生物碱的共同核心结构，例如长春花碱，echitamine和aspidosphyllineA。
• Nine-Step Enantioselective Total Synthesis of (+)-Minfiensine
  作者：Spencer B. Jones、Bryon Simmons、David W. C. MacMillan

  DOI：10.1021/ja906472m

  日期：2009.9.30

  An enantioselective total synthesis of the Strychnos alkaloid (+)-minfiensine has been accomplished. Prominent features of this synthesis include (i) a new enantioselective organocatalytic Diels-Alder/amine cyclization sequence to build the central tetracyclic pyrroloindoline framework in four steps from commercial materials and (ii) a 6-exo-dig radical cyclization to forge the final piperidinyl ring system. This total synthesis of (+)-minfiensine was completed in nine chemical steps and 21% overall yield.
• Sequential Catalytic Asymmetric Heck−Iminium Ion Cyclization:  Enantioselective Total Synthesis of the <i>Strychnos </i>Alkaloid Minfiensine
  作者：Amy B. Dounay、Larry E. Overman、Aaron D. Wrobleski

  DOI：10.1021/ja0533895

  日期：2005.7.1

  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).