(1S,3R)-benzyl 1-((E)-4-methoxy-4-oxobut-2-en-1-yl)-2,3,4,9-tetrahydro-1H-pyrio[3,4-b]indole-3-carboxylate

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 哈马拉生物碱
• 英文名称: (1S,3R)-benzyl 1-((E)-4-methoxy-4-oxobut-2-en-1-yl)-2,3,4,9-tetrahydro-1H-pyrio[3,4-b]indole-3-carboxylate
• 英文别名: benzyl (1S,3R)-1-[(E)-4-methoxy-4-oxobut-2-enyl]-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylate
• 化学式: C₂₄H₂₄N₂O₄
• 分子量: 404.466
• InChiKey: NTEVBCJGVBHRMK-BSQFJSTMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  30
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  80.4
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (1S,3R)-benzyl 1-((E)-4-methoxy-4-oxobut-2-en-1-yl)-2,3,4,9-tetrahydro-1H-pyrio[3,4-b]indole-3-carboxylate 在 N-甲基吗啉 、 三乙基硅烷 、 4-二甲氨基吡啶 、 bis(1,5-cyclooctadiene)nickel (0) 、 正丁基锂 、 偶氮二异丁腈 、 三正丁基氢锡 、 palladium diacetate 、 potassium carbonate 、 三乙胺 、 二异丙胺 、 氯甲酸异丁酯 作用下， 以 四氢呋喃 、 正己烷 、 甲苯 、 乙腈 、 苯 为溶剂， 反应 18.83h， 生成 (Z,2R,12bS)-tert-butyl 2-[di(methoxycarbonyl)methyl]-3-ethylidene-1,2,3,4,6,7-hexahydroindolo[2,3-a]quinolizine-12(12bH)-carboxylate
  参考文献：
  名称：

  Geissoschizine骨架的生物启发性氧化环化反应，用于马瓦库拉生物碱的对映选择性全合成。

  摘要：

  报道了马卡武兰生物碱，（+）-二萜H，（+）-16-羟甲基-pleiocarpamine和（+）-16- epi -pleiocarpamine及其假定的生物合成前体16-formyl -pleiocarpamine的对映体选择性合成。该单萜吲哚生物碱家族是一个选择的目标，因为它的某些成员是复杂的双吲哚生物碱的亚基，例如双叶茶碱。受生物合成假说的启发，探索了从Geissoschizine框架形成N1-C16键的氧化偶联方法。脂族氮中心的季铵化是实现KHMDS / I 2诱导的氧化偶联的关键，因为它掩盖了脂族氮中心的亲核性并锁定了所需的顺式构象。

  DOI：

  10.1002/anie.201905227
• 作为产物：
  描述：

  D-色氨酸 在 氯化亚砜 、 溶剂黄146 作用下， 以 二氯甲烷 为溶剂， 反应 79.67h， 生成 (1S,3R)-benzyl 1-((E)-4-methoxy-4-oxobut-2-en-1-yl)-2,3,4,9-tetrahydro-1H-pyrio[3,4-b]indole-3-carboxylate
  参考文献：
  名称：

  Geissoschizine骨架的生物启发性氧化环化反应，用于马瓦库拉生物碱的对映选择性全合成。

  摘要：

  报道了马卡武兰生物碱，（+）-二萜H，（+）-16-羟甲基-pleiocarpamine和（+）-16- epi -pleiocarpamine及其假定的生物合成前体16-formyl -pleiocarpamine的对映体选择性合成。该单萜吲哚生物碱家族是一个选择的目标，因为它的某些成员是复杂的双吲哚生物碱的亚基，例如双叶茶碱。受生物合成假说的启发，探索了从Geissoschizine框架形成N1-C16键的氧化偶联方法。脂族氮中心的季铵化是实现KHMDS / I 2诱导的氧化偶联的关键，因为它掩盖了脂族氮中心的亲核性并锁定了所需的顺式构象。

  DOI：

  10.1002/anie.201905227

文献信息

• Bioinspired Divergent Oxidative Cyclizations of Geissoschizine: Total Synthesis of (–)‐17‐nor‐Excelsinidine, (+)‐16‐ <i>epi</i> ‐Pleiocarpamine, (+)‐16‐Hydroxymethyl‐Pleiocarpamine and (+)‐Taberdivarine H
  作者：Maxime Jarret、Aurélien Tap、Victor Turpin、Natacha Denizot、Cyrille Kouklovsky、Erwan Poupon、Laurent Evanno、Guillaume Vincent

  DOI：10.1002/ejoc.202000962

  日期：2020.10.31

  To synthesize excelsinidines and mavacurans alkaloids, bio‐inspired oxidative cyclizations of (+)‐geissochizine and analogues mediated by KHMDS/I2 were studied. Applied to geissoschizine, the N4–C16 bond formation led to excelsinidines core. Quaternization of the aliphatic nitrogen was necessary to access the mavacurans core (N1–C16 bond). Alternatively, 17‐nor‐excelsinidine was synthetized via an

  为了合成excelsinidines和mavacurans生物碱，研究了由KHMDS / I 2介导的（+）-geissochizine及其类似物的生物启发性氧化环化作用。应用于Geissoschizine时，N4-C16键的形成导致了Excelsinidines的核心。脂族氮的季铵化是进入马六甲聚糖核心（N1-C16键）所必需的。或者，通过α-氯内酰胺的分子内亲核取代合成17-或excelsinidine。
• Bioinspired Oxidative Cyclization of the Geissoschizine Skeleton for the Total Synthesis of (−)-17-nor-Excelsinidine
  作者：Maxime Jarret、Aurélien Tap、Cyrille Kouklovsky、Erwan Poupon、Laurent Evanno、Guillaume Vincent

  DOI：10.1002/anie.201802610

  日期：2018.9.17

  report the first total synthesis of (−)‐17‐nor‐excelsinidine, a zwitterionic monoterpene indole alkaloid that displays an unusual N4−C16 connection. Inspired by the postulated biosynthesis, we explored an oxidative coupling approach from the geissoschizine framework to forge the key ammonium–acetate connection. Two strategies allowed us to achieve this goal, namely an intramolecular nucleophilic substitution

  我们报告了（−）-17-nor-excelsinidine的第一个全合成，这是一种两性离子单萜吲哚生物碱，显示出异常的N4-C16连接。受假定的生物合成的启发，我们探索了Geissoschizine骨架的氧化偶联方法，以建立关键的醋酸铵连接。有两种策略使我们得以实现这一目标，即在16-氯内酰胺上用N4氮原子进行分子内亲核取代或从Geissoschizine的烯醇化物中直接进行I 2介导的N4-C16氧化偶联。
• Applications of Vinylogous Mannich Reactions. Asymmetric Synthesis of the Heteroyohimboid Alkaloids (-)-Ajmalicine, (+)-19-epi-Ajmalicine, and (-)-Tetrahydroalstonine
  作者：Stephen F. Martin、Cameron W. Clark、Jeffrey W. Corbett

  DOI：10.1021/jo00115a044

  日期：1995.5

  The vinylogous Mannich additions of 1-[(trialkylsilyl)oxy]butadienes to the acyl iminium salt derived from 7 proceeded with a modest degree of stereoselectivity to give a mixture (1.8:1) of 8 and 9. The triene 8 underwent an intramolecular hetero Diels-Alder reaction to give the pentacyclic intermediate 10. Decarboxylation of 10 according to the Barton protocol led to 13, which was then elaborated to (-)-tetrahydroalstonine (1) by a straightforward sequence of reactions. This asymmetric synthesis of 1 required only 10 steps from readily available L-tryptophan. On the other hand, the related vinylogous Mannich addition of a vinyl ketene acetals to 16 were highly stereoselective giving the corresponding trans-substituted hydrocarboline as the only detectable product. Subsequent reaction of this adduct with methyl vinyl ketone followed by cyclization of the intermediate 18 gave the key tetracyclic intermediate 19. Removal of the carboxyl group from the C(5) position of 19 following the Barton procedure gave the ketone 20, which was converted into (-)-ajmalicine (2) in three steps by a known procedure. Alternatively, hydride reduction of the tetracyclic amine 19 gave the alcohol 22, which was subjected to a modified Mitsunobu reaction; selective hydrolysis of the intermediate triester led to the lactone 24. Radical decarboxylation via the Barton procedure gave an intermediate lactone that was converted into (+)-19-epi-ajmalicine (3) in two steps. Removal of the carboxyl presented pathways to both (-)-ajmalicine (2) and (+)-19-epi-ajmalicine (3). Thus, the asymmetric syntheses of 2 and 3 were completed by concise sequences of reactions requiring only 11 and 13 steps, respectively, from D-tryptophan.