methyl (4aS,12aS)-4a-ethyl-1-hydroxy-7-(2-oxoethyl)-2,3,4,12a-tetrahydroindolo[1,2-a][1,8]naphthyridine-6-carboxylate | 163814-12-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: methyl (4aS,12aS)-4a-ethyl-1-hydroxy-7-(2-oxoethyl)-2,3,4,12a-tetrahydroindolo[1,2-a][1,8]naphthyridine-6-carboxylate
• CAS: 163814-12-8
• 化学式: C₂₁H₂₄N₂O₄
• 分子量: 368.433
• InChiKey: VJLXPMAWXKLWMS-RTWAWAEBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  71.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  methyl (4aS,12aS)-4a-ethyl-1-hydroxy-7-(2-oxoethyl)-2,3,4,12a-tetrahydroindolo[1,2-a][1,8]naphthyridine-6-carboxylate 在 sodium cyanoborohydride 、 sodium hydroxide 作用下， 以 溶剂黄146 、 水 为溶剂， 反应 2.5h， 以100%的产率得到
  参考文献：
  名称：

  Semisynthesis of (+)- and (−)-goniomitine from (−)- and (+)-vincadifformine

  摘要：

  The first biomimetic semisynthesis of goniomitine has been accomplished in nine steps with 11% overall yield starting from vincadifformine. Natural (-)- and unnatural (+)-goniomitine were prepared from (+)- and (-)-vincadifformine, respectively. The evaluation of the antiproliferative effect of both enantiomers proved unnatural (+)-goniomitine to be more potent, but this enantiomer as well as some close derivatives displayed a moderate activity only. (c) 2012 Published by Elsevier Ltd.

  DOI：

  10.1016/j.tet.2012.11.084
• 作为产物：
  描述：

  methyl (1R,10R,12S,18S,20S)-10-chloro-12-ethyl-18-hydroxy-17-oxa-8,16-diazapentacyclo[10.7.1.01,9.02,7.016,20]icosa-2,4,6,8-tetraene-10-carboxylate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 15.0h， 以52%的产率得到methyl (4aS,12aS)-4a-ethyl-1-hydroxy-7-(2-oxoethyl)-2,3,4,12a-tetrahydroindolo[1,2-a][1,8]naphthyridine-6-carboxylate
  参考文献：
  名称：

  New Rearrangement of an Aspidosperma Alkaloid. The First Biomimetic Entry in the Goniomitine Skeleton

  摘要：

  The first biomimetic approach to the skeleton of goniomitine (12) from an Aspidosperma alkaloid is described. With 16-chloro-1-dehydro-5-methoxyvincadifforme (4) (easily available from vincadifformine (1) as starting material, the rearrangement is performed in two steps: (a) Oxidation of 4 by m-CPBA followed by methanolysis affords the hemiketal 10 with a tetrahydro-1,2-oxazine structure for ring C, and (b) acid-catalyzed reaction on 10 provides either a mixture of both rearranged compounds 15 and 16 or 15 alone according to reaction time. Mechanisms of formation of 10, 15, and 16 are discussed.

  DOI：

  10.1021/jo00116a009

文献信息

• Synthesis of a novel series of cytotoxic bisindole alkaloids
  作者：Marion Raoul、Corinne Schaeffer、Stéphane Léonce、Alain Pierré、Ghanem Atassi、Reynald Hocquemiller、Guy Lewin

  DOI：10.1016/s0960-894x(00)00600-4

  日期：2001.1

  Original cytotoxic bisindole alkaloids with a 1,2,3,4-tetrahydroquinoline bridge were synthesized by reductive amination with various anilines. The most cytotoxic compounds display a high and dose-dependent cell cycle effect with accumulation in the G1 phase. Influence of substitution of the starting aniline on the reaction and on cytotoxicity of produced dimers was pointed out.

  通过与各种苯胺的还原胺化反应合成具有1,2,3,4-四氢喹啉桥的原始细胞毒性双吲哚生物碱。最具细胞毒性的化合物显示出高剂量依赖性的细胞周期效应，并在G1期积累。指出了起始苯胺的取代对反应和所产生的二聚体的细胞毒性的影响。
• Access to New Cytotoxic Bisindole Alkaloids by a Modified Borch Reductive Amination Process
  作者：Guy Lewin、Corinne Schaeffer、Reynald Hocquemiller、Edgar Jacoby、Stéphane Léonce、Alain Pierré、Ghanem Atassi

  DOI：10.3987/com-00-9001

  日期：——

  A slight modification of the Borch reductive amination method (delayed addition of NaBH3CN) was applied to an indole aldehyde compound, analog of the natural alkaloid, goniomitine. This reaction led to a series of new cytotoxic bisindole alkaloids with a 1,2,3,4-tetrahydroquinoline bridge.
• Semisynthesis of (+)- and (−)-goniomitine from (−)- and (+)-vincadifformine
  作者：Guy Lewin、Guillaume Bernadat、Geneviève Aubert、Thierry Cresteil

  DOI：10.1016/j.tet.2012.11.084

  日期：2013.2

  The first biomimetic semisynthesis of goniomitine has been accomplished in nine steps with 11% overall yield starting from vincadifformine. Natural (-)- and unnatural (+)-goniomitine were prepared from (+)- and (-)-vincadifformine, respectively. The evaluation of the antiproliferative effect of both enantiomers proved unnatural (+)-goniomitine to be more potent, but this enantiomer as well as some close derivatives displayed a moderate activity only. (c) 2012 Published by Elsevier Ltd.
• New Rearrangement of an Aspidosperma Alkaloid. The First Biomimetic Entry in the Goniomitine Skeleton
  作者：Guy Lewin、Corinne Schaeffer、Pierre Herve Lambert

  DOI：10.1021/jo00116a009

  日期：1995.6

  The first biomimetic approach to the skeleton of goniomitine (12) from an Aspidosperma alkaloid is described. With 16-chloro-1-dehydro-5-methoxyvincadifforme (4) (easily available from vincadifformine (1) as starting material, the rearrangement is performed in two steps: (a) Oxidation of 4 by m-CPBA followed by methanolysis affords the hemiketal 10 with a tetrahydro-1,2-oxazine structure for ring C, and (b) acid-catalyzed reaction on 10 provides either a mixture of both rearranged compounds 15 and 16 or 15 alone according to reaction time. Mechanisms of formation of 10, 15, and 16 are discussed.