rhazinilam | 883456-51-7

• 分子结构分类: 有机化合物 - 苯类化合物
• 英文名称: rhazinilam
• 英文别名: (12R)-12-ethyl-8,16-diazatetracyclo[10.6.1.02,7.016,19]nonadeca-1(19),2,4,6,17-pentaen-9-one
• CAS: 883456-51-7
• 化学式: C₁₉H₂₂N₂O
• 分子量: 294.396
• InChiKey: VLQAFTDOIRUYSZ-LJQANCHMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  22
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  34
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  rhazinilam 在 lithium aluminium tetrahydride 作用下， 生成 (12S)-12-ethyl-8,16-diazatetracyclo[10.6.1.02,7.016,19]nonadeca-1(19),2,4,6,17-pentaene
  参考文献：
  名称：

  Hemisynthesis of rhazinilam analogues: structure - activity relationships on tubulin-microtubule system

  摘要：

  Semi-synthesis of derivatives of rhazinilam, an antitubulin compound, delineated some molecular features necessary for biological activity. In the course of this study, the formation of rhazinilam from 1,2-didehydroaspidospermidine is reexamined and a new mechanism is proposed. (C) 1997 Elsevier Science Ltd.

  DOI：

  10.1016/s0960-894x(97)00391-0
• 作为产物：
  描述：

  eburenine 在 氧气 、 iron(II) sulfate 、 间氯过氧苯甲酸 作用下， 生成 rhazinilam
  参考文献：
  名称：

  Hemisynthesis of rhazinilam analogues: structure - activity relationships on tubulin-microtubule system

  摘要：

  Semi-synthesis of derivatives of rhazinilam, an antitubulin compound, delineated some molecular features necessary for biological activity. In the course of this study, the formation of rhazinilam from 1,2-didehydroaspidospermidine is reexamined and a new mechanism is proposed. (C) 1997 Elsevier Science Ltd.

  DOI：

  10.1016/s0960-894x(97)00391-0

文献信息

• Short Enantioselective Total Synthesis of (−)-Rhazinilam Using a Gold(I)-Catalyzed Cyclization
  作者：Valentin Magné、Charlotte Lorton、Angela Marinetti、Xavier Guinchard、Arnaud Voituriez

  DOI：10.1021/acs.orglett.7b02210

  日期：2017.9.15

  steps involve two metal-catalyzed processes: the enantioselective gold(I)-catalyzed cycloisomerization of an allene-functionalized pyrrole and the palladium-catalyzed hydrocarboxylation of a vinyl moiety with formate as a CO surrogate. This novel strategy represents the shortest and highest yielding enantioselective total synthesis of (−)-rhazinilam.

  （R）-（-）-Rhazinilam已通过9个步骤合成，总产率为20％。关键步骤涉及两个金属催化的过程：对映体选择性金（I）催化的烯丙基官能化吡咯的环异构化和钯催化的乙烯基部分与甲酸酯作为CO替代物的加氢羧化反应。这种新颖的策略代表了（-）-rhazinilam的最短和最高产量的对映选择性全合成。
• Protecting-Group-Free Total Synthesis of (−)-Rhazinilam and (−)-Rhazinicine using a Gold-Catalyzed Cascade Cyclization
  作者：Kenji Sugimoto、Kazuki Toyoshima、Shiori Nonaka、Kenta Kotaki、Hirofumi Ueda、Hidetoshi Tokuyama

  DOI：10.1002/anie.201303067

  日期：2013.7.8

  ‘Rhaz'zmatazz: A total synthesis of (−)‐rhazinilam and the first asymmetric total synthesis of (−)‐rhazinicine were accomplished by using constructing the indolizinone core through the gold‐catalyzed cyclization of a fully elaborated linear ynamide. The scope and generality of this cascade reaction for the construction of highly substituted indolizinones were also investigated.

  'Rhaz'zmatazz：（-）-rhazinilam的全合成和（-）-rhazinicine的第一个不对称全合成是通过使用金精催化的完全精制的线性乙酰胺环化吲哚嗪酮核心完成的。还研究了该级联反应用于构建高度取代的吲哚嗪酮的范围和一般性。
• Au(I)-Catalyzed Annulation of Enantioenriched Allenes in the Enantioselective Total Synthesis of (−)-Rhazinilam
  作者：Zuosheng Liu、Andrew S. Wasmuth、Scott G. Nelson

  DOI：10.1021/ja0629110

  日期：2006.8.1

  a unique entry to optically active heterocycles. Asymmetric quaternary carbons can be installed with concurrent heterocycle annulation utilizing this methodology. The enantioenriched allenes are conveniently obtained by catalytic asymmetric acyl halide-aldehyde cyclocondensations and SN2' ring opening of the resulting enantioenriched beta-lactones. An enantioselective total synthesis of (-)-rhazinilam

  高度立体选择性的 Au(I) 催化吡咯加成到富含对映体的丙二烯提供了独特的光学活性杂环入口。不对称季碳可以使用这种方法与并发杂环环化一起安装。富含对映体的丙二烯可以通过催化不对称酰卤-醛环缩合反应和所得的富含对映体的β-内酯的SN2'开环方便地获得。(-)-rhazinilam 的对映选择性全合成突出了该反应技术在靶向合成中的潜在效用。
• Synthesis and biological evaluation of B-ring analogues of (−)-rhazinilam
  作者：Anne Décor、Barbara Monse、Marie-Thérèse Martin、Angèle Chiaroni、Sylviane Thoret、Daniel Guénard、Françoise Guéritte、Olivier Baudoin

  DOI：10.1016/j.bmc.2005.11.011

  日期：2006.4

  and C-16alpha analogues have the same conformation as rhazinilam, whereas C-16beta analogues adopt a different conformation for rings B and D. All N-1 and C-16 analogues were less active than rhazinilam on tubulin, though analogues 5a, 6aalpha, 6balpha, and 6f having the less bulky substituents retained close affinities. A few analogues either active (like 6f) or inactive (like 5o) on tubulin showed

  从天然产物中合成了具有11或12元B环，带有一个环内氨基甲酸酯基团或一个氨基酸残基的鼠李糖胺1的三个大环类似物。这些类似物3和4对微管蛋白表现出非常低的活性。还从鼠李糖胺区域选择性地合成了鼠李糖胺的三十个N-1和C-16取代的类似物。立体化学分析显示，N-1和C-16alpha类似物的构型与鼠李敏相同，而C-16beta类似物对环B和D的构型不同。所有N-1和C-16类似物在微管蛋白上的活性均不及鼠李敏。 ，尽管具有较小体积取代基的类似物5a，6aalpha，6balpha和6f保持了亲和力。对微管蛋白有活性的一些类似物（如6f）或无活性的类似物（如5o）显示出对KB癌细胞生长的显着抑制作用。
• Enantioselective Total Syntheses of (−)-Rhazinilam, (−)-Leucomidine B, and (+)-Leuconodine F
  作者：Dylan Dagoneau、Zhengren Xu、Qian Wang、Jieping Zhu

  DOI：10.1002/anie.201508906

  日期：2016.1.11

  A divergent total synthesis of three structurally distinct natural products from imine 9 was accomplished through an approach featuring: 1) a Pd‐catalyzed decarboxylative cross‐coupling, and 2) heteroannulation of 9 with bromoacetaldehyde and oxalyl chloride to give tetrahydroindolizine 6 and dioxopyrrole 7, respectively. The former was converted into (−)‐rhazinilam, while the latter was converted

  通过以下方法完成了亚胺9的三种结构不同的天然产物的不同总合成：1）Pd催化的脱羧交叉偶联，以及2）9与溴乙醛和草酰氯的杂环化，得到四氢吲哚嗪6和二氧杂吡咯7，分别。前者转化为（-）-rhazinilam，而后者转化为（-）-leucomidine B和（+）-leuconodineF。通过使用均相钯催化剂，底物定向的空间非偏置双键高度非对映选择性还原发展了。隐隐胞苷B观察到自诱导的非对映异构性（SIDA）现象。