(1S,4R,7S,9R)-5-(2-azidobenzoyl)-4-methyl-9-(2-methylbut-3-en-2-yl)-2,5,16-triazatetracyclo[7.7.0.02,7.010,15]hexadeca-10,12,14-triene-3,6-dione | 159333-24-1

• 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: (1S,4R,7S,9R)-5-(2-azidobenzoyl)-4-methyl-9-(2-methylbut-3-en-2-yl)-2,5,16-triazatetracyclo[7.7.0.02,7.010,15]hexadeca-10,12,14-triene-3,6-dione
• CAS: 159333-24-1
• 化学式: C₂₆H₂₆N₆O₃
• 分子量: 470.531
• InChiKey: VCBJSSYMKSKGEV-BXVKCURFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  35
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  84.1
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (1S,4R,7S,9R)-5-(2-azidobenzoyl)-4-methyl-9-(2-methylbut-3-en-2-yl)-2,5,16-triazatetracyclo[7.7.0.02,7.010,15]hexadeca-10,12,14-triene-3,6-dione 在 三丁基膦 、 N,N-二异丙基乙胺 作用下， 以 苯 为溶剂， 反应 36.0h， 生成 (7R,9aR,14bR,15aS)-10-acetyl-10,14b,15,15a-tetrahydro-7-methyl-14b-(2-methylbut-3-en-2-yl)indolo[3'',2'': 4',5']pyrrolo[2',1': 3,4]pyrazino[2,1-b]quinazoline-5,8(7H,9aH)dione
  参考文献：
  名称：

  Total Synthesis of 5-N-Acetylardeemin and Amauromine:  Practical Routes to Potential MDR Reversal Agents

  摘要：

  The total synthesis of the title compounds has been accomplished. The key step involves the kinetic stereoselective conversion of 19 --> 20. The synthesis of 20 represents for the first time a direct method for constructing exo-pyrroloindoles from protected tryptophans in a highly diastereoselective manner. This step was followed by reverse prenylation (see conversion of 20 --> 27). Using the methodology worked out for the titled compounds, a practical synthesis of several promising MDR reversal agents was possible. Biological data that provided the basis for selection of candidates for advanced study are presented. Preliminary profiling of the zones of the molecules that are responsive to changes while still retaining MDR reversal ability are described. On the basis of these findings, compounds 2, 50, and 51 were selected for more extensive biological follow-up.

  DOI：

  10.1021/ja991558d
• 作为产物：
  描述：

  L-色氨酸甲酯 在 吡啶 、 4-二甲氨基吡啶 、 sodium hydroxide 、 三聚氟氰 、 2,6-二叔丁基吡啶 、 碘代三甲硅烷 、 氨 、 四丁基硫酸氢铵 、 4-甲基苯磺酸吡啶 、 双(三甲基硅烷基)氨基钾 、 碳酸氢钠 、 三氟甲烷磺酸甲酯 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 、 乙腈 为溶剂， 生成 (1S,4R,7S,9R)-5-(2-azidobenzoyl)-4-methyl-9-(2-methylbut-3-en-2-yl)-2,5,16-triazatetracyclo[7.7.0.02,7.010,15]hexadeca-10,12,14-triene-3,6-dione
  参考文献：
  名称：

  Total Synthesis of 5-N-Acetylardeemin and Amauromine:  Practical Routes to Potential MDR Reversal Agents

  摘要：

  The total synthesis of the title compounds has been accomplished. The key step involves the kinetic stereoselective conversion of 19 --> 20. The synthesis of 20 represents for the first time a direct method for constructing exo-pyrroloindoles from protected tryptophans in a highly diastereoselective manner. This step was followed by reverse prenylation (see conversion of 20 --> 27). Using the methodology worked out for the titled compounds, a practical synthesis of several promising MDR reversal agents was possible. Biological data that provided the basis for selection of candidates for advanced study are presented. Preliminary profiling of the zones of the molecules that are responsive to changes while still retaining MDR reversal ability are described. On the basis of these findings, compounds 2, 50, and 51 were selected for more extensive biological follow-up.

  DOI：

  10.1021/ja991558d

文献信息

• Total Synthesis of (−)-Ardeemin
  作者：Bin He、Hao Song、Yu Du、Yong Qin

  DOI：10.1021/jo802216z

  日期：2009.1.2

  Total synthesis of potent anti-MDR indole alkaloids (−)-ardeemin and its N-acyl analogues has been accomplished from l-tryptophan with about 2% overall yield in 20 steps. The key step depended on the newly developed three-step one-pot cascade reaction of 7 with diazoester 8 via intermolecular cyclopropanation, ring opening, and ring closure to assemble the chiral 3-substituted hexahydropyrrolo[2,3-b]indole

  有效的抗MDR吲哚生物碱（-）-ardeemin及其N-酰基类似物的全合成已由L-色氨酸以20步的总产率完成了约2％。关键步骤取决于分子间环丙烷化，开环和闭环，使7与重氮酸酯8进行三步一锅级联反应，以组装手​​性3-取代的六氢吡咯并[2,3-b]吲哚4a。
• ANALOGUES OF N-ACETYLARDEEMIN, METHOD OF PREPARATION AND USES THEREOF
  申请人：The Trustees of Columbia University in the City of New York

  公开号：EP0815111B1

  公开（公告）日：2007-10-10
• Stereoselective Total Syntheses of Amauromine and 5-N-Acetylardeemin. A Concise Route to the Family of "Reverse-Prenylated" Hexahydropyrroloindole Alkaloids
  作者：Stephen P. Marsden、Kristopher M. Depew、Samuel J. Danishefsky

  DOI：10.1021/ja00103a034

  日期：1994.11
• Total Synthesis of 5-<i>N</i>-Acetylardeemin and Amauromine:  Practical Routes to Potential MDR Reversal Agents
  作者：Kristopher M. Depew、Stephen P. Marsden、Danuta Zatorska、Andrzej Zatorski、William G. Bornmann、Samuel J. Danishefsky

  DOI：10.1021/ja991558d

  日期：1999.12.1

  The total synthesis of the title compounds has been accomplished. The key step involves the kinetic stereoselective conversion of 19 --> 20. The synthesis of 20 represents for the first time a direct method for constructing exo-pyrroloindoles from protected tryptophans in a highly diastereoselective manner. This step was followed by reverse prenylation (see conversion of 20 --> 27). Using the methodology worked out for the titled compounds, a practical synthesis of several promising MDR reversal agents was possible. Biological data that provided the basis for selection of candidates for advanced study are presented. Preliminary profiling of the zones of the molecules that are responsive to changes while still retaining MDR reversal ability are described. On the basis of these findings, compounds 2, 50, and 51 were selected for more extensive biological follow-up.