3-ethenyl-3,7,7,10-tetramethyl-4,16-dioxo-10-azatetracyclo[6.6.1.1^2,6.0^11,15]-hexadeca-1(14),8,11(15),12-tetraene-2-carbaldehyde

• 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: 3-ethenyl-3,7,7,10-tetramethyl-4,16-dioxo-10-azatetracyclo[6.6.1.1^2,6.0^11,15]-hexadeca-1(14),8,11(15),12-tetraene-2-carbaldehyde
• 英文别名: 3-ethenyl-3,7,7,10-tetramethyl-4,16-dioxo-10-azatetracyclo[6.6.1.1(2,6).0(11,15)]hexadeca-1(15),8,11,13-tetraene-2-carbaldehyde；(2R,3S,6R)-3-ethenyl-3,7,7,10-tetramethyl-4,16-dioxo-10-azatetracyclo[6.6.1.12,6.011,15]hexadeca-1(15),8,11,13-tetraene-2-carbaldehyde
• 化学式: C₂₂H₂₃NO₃
• 分子量: 349.43
• InChiKey: KDLGNEZVGQCFHP-CUJSYCCXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  26
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  56.1
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-ethenyl-3,7,7,10-tetramethyl-4,16-dioxo-10-azatetracyclo[6.6.1.1^2,6.0^11,15]-hexadeca-1(14),8,11(15),12-tetraene-2-carbaldehyde 在 双(三甲基硅烷基)氨基钾 、 N-溴代丁二酰亚胺(NBS) 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 1.02h， 以91%的产率得到(2R,3S,5S,6R)-5-bromo-3-ethenyl-3,7,7,10-tetramethyl-4,16-dioxo-10-azatetracyclo[6.6.1.12,6.011,15]hexadeca-1(15),8,11,13-tetraene-2-carbaldehyde
  参考文献：
  名称：

  N-甲基维多林酮D异腈的全合成

  摘要：

  描述了 N-methylwelwitindolinone D 异腈的简明全合成，这是一个复杂的含双环 [4.3.1] 癸烷的吲哚生物碱家族中第一个合成的。天然产物的完整碳核通过路易斯酸介导的烷基化偶联快速组装，然后直接进行钯催化的烯醇芳基化反应。五环的最后一个环通过吲哚氧化/环化引入，异腈通过醛重排为异硫氰酸酯然后脱硫安装。

  DOI：

  10.1021/ja201834u
• 作为产物：
  描述：

  4-(tert-Butyldimethylsilyloxy)-3-methylcyclohex-2-en-1-one 在 copper(I) bromide dimethylsulfide complex 、 三叔丁基膦 、 氢氟酸 、 palladium diacetate 、 双(三甲基硅烷基)氨基钾 、 碳酸氢钠 、 potassium carbonate 、 戴斯-马丁氧化剂 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 甲苯 、 乙腈 为溶剂， 反应 31.28h， 生成 3-ethenyl-3,7,7,10-tetramethyl-4,16-dioxo-10-azatetracyclo[6.6.1.1^2,6.0^11,15]-hexadeca-1(14),8,11(15),12-tetraene-2-carbaldehyde
  参考文献：
  名称：

  N-甲基维多林酮D异腈的全合成

  摘要：

  描述了 N-methylwelwitindolinone D 异腈的简明全合成，这是一个复杂的含双环 [4.3.1] 癸烷的吲哚生物碱家族中第一个合成的。天然产物的完整碳核通过路易斯酸介导的烷基化偶联快速组装，然后直接进行钯催化的烯醇芳基化反应。五环的最后一个环通过吲哚氧化/环化引入，异腈通过醛重排为异硫氰酸酯然后脱硫安装。

  DOI：

  10.1021/ja201834u

文献信息

• Studies toward welwitindolinones: formal syntheses of N-methylwelwitindolinone C isothiocyanate and related natural products
  作者：Tsung-hao Fu、William T. McElroy、Mariam Shamszad、Richard W. Heidebrecht、Brian Gulledge、Stephen F. Martin

  DOI：10.1016/j.tet.2013.03.010

  日期：2013.7

  welwitindolinones 5–8 were achieved by the independent synthesis of 79. The synthesis featured a Lewis acid-mediated coupling between a heteroaryl carbinol and bis-TMS enol ether, an intramolecular enolate arylation, and an unprecedented intramolecular allylic alkylation of a γ-acyloxyenone.

  正式合成Ñ -methylwelwitindolinoneÇ异硫氰酸酯（4）等几个welwitindolinones 5 - 8分别通过独立合成实现79。该合成以路易斯酸介导的杂芳基甲醇和双-TMS 烯醇醚之间的偶联、分子内烯醇芳基化和前所未有的 γ-酰氧烯酮分子内烯丙基烷基化为特征。
• Lessons learned while traversing the welwitindolinone alkaloids obstacle course
  作者：Vikram Bhat、James A. MacKay、Viresh H. Rawal

  DOI：10.1016/j.tet.2011.09.088

  日期：2011.12

  We recount several unexpected results observed in the course of our work toward the synthesis of welwitindolinone alkaloids. The surprising results provide an opportunity to refine one's understanding of the interplay between chemical structure and reactivity. (C) 2011 Elsevier Ltd. All rights reserved.
• Formal Syntheses of Naturally Occurring Welwitindolinones
  作者：Tsung-hao Fu、William T. McElroy、Mariam Shamszad、Stephen F. Martin

  DOI：10.1021/ol301424h

  日期：2012.8.3

  The formal syntheses of N-methylwelwitindolinone C isothiocyanate, N-methylwelwitindolinone C isonitrile, N-methylwelwitindolinone D isonitrile, 3-hydroxy-N-methylwelwitindolinone C isothiocyanate, and 3-hydroxy-N-methylwelwitindolinone C isonitrile are reported. The synthesis features several novel processes, Including a Lewis acid mediated coupling between a benzylic-type heteroaromatic alcohol and a highly functionalized silyl ketene acetal, an intramolecular enolate arylation, and a regioselective, Pd(0)-catalyzed pi-allylic cyclization of a gamma-benzoyloxy enone moiety that is revealed by unmasking a furan ring.
• A Unified Route to the Welwitindolinone Alkaloids: Total Syntheses of (−)-<i>N</i>-Methylwelwitindolinone C Isothiocyanate, (−)-<i>N</i>-Methylwelwitindolinone C Isonitrile, and (−)-3-Hydroxy-<i>N</i>-methylwelwitindolinone C Isothiocyanate
  作者：Kevin M. Allan、Kenichi Kobayashi、Viresh H. Rawal

  DOI：10.1021/ja210793x

  日期：2012.1.25

  As part of a comprehensive strategy to the welwitindolinone alkaloids possessing a bicyclo[4.3.1]decane core, we report herein concise asymmetric total syntheses of (-)-N-methylwelwitindolinone C isothiocyanate (2a), (-)-N-methylwelwitindolinone C isonitrile (2b), and (-)-3-hydroxy-N-methylwelwitindolinone C isothiocyanate (3a) from a common tetracyclic intermediate. The crucial vinyl chloride moiety was installed through electrophilic chlorination of a hydrazone, but only after adjustment of reactivity to circumvent a facile skeletal rearrangement. Selective desulfurization and oxidation of 2a provided access to 2b and 3a, respectively. Notably, this work provides corrected H-1 and C-13 NMR spectral data for 3a.