(-)-14-O-acetyl-5-formylindolactam-V | 153997-47-8

• 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: (-)-14-O-acetyl-5-formylindolactam-V
• CAS: 153997-47-8
• 化学式: C₂₀H₂₅N₃O₄
• 分子量: 371.436
• InChiKey: GCCCQTDBJYSMQW-YJBOKZPZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.05
• 重原子数：
  27.0
• 可旋转键数：
  4.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  91.5
• 氢给体数：
  2.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  (-)-14-O-acetyl-5-formylindolactam-V 在 lithium aluminium tetrahydride 、 三氯化铝 作用下， 以 四氢呋喃 为溶剂， 反应 0.17h， 生成 Acetic acid (10S,13S)-10-isopropyl-7,9-dimethyl-11-oxo-3,9,12-triaza-tricyclo[6.6.1.0^4,15]pentadeca-1,4,6,8(15)-tetraen-13-ylmethyl ester
  参考文献：
  名称：

  Synthesis and Biological Activities of New Conformationally Restricted Analogues of (−)-Indolactam-V:  Elucidation of the Biologically Active Conformation of the Tumor-Promoting Teleocidins

  摘要：

  The tumor-promoting teleocidins and their core structure (-)-indolactam-V (1) exist in two stable conformers in solution at room temperature. The cis amide assumes a twist conformation while the trans amide exists in a sofa form. In order to identify the biologically active conformation of the teleocidins, we have synthesized new twist-restricted analogues 5a and 6 based on an aza-Claisen rearrangement of (-)-N-13-desmethyl-N-13-allylindolactam-V (3) and a sofa-restricted analogue, (-)-5-methylindolactam-V (22). The activities of these new compounds were evaluated in three in vitro bioassays associated with in vivo tumor-promoting activity: binding to the protein kinase C regulatory domain, induction of the Epstein-Barr virus early antigen, and stimulation of radioactive inorganic phosphate incorporation into phospholipids of HeLa cells. These three biological activities correlated well for each derivative, Twist-restricted analogues 5a and 6 showed significant activities in the three assays, comparable to 1 itself. In contrast, sofa-restricted 22 showed little activity related to tumor promotion. Introduction of a prenyl group into position 7 or 18 of 5a and 6 significantly enhanced the activity while sofa-restricted (-)-5-prenylindolactam-V (23) showed only very weak activity. These results indicate that the active conformation of the teleocidins and 1 is close to the twist form. This is the first evidence beating on the active conformation of the teleocidins based on conformationally restricted analogues with an intact indolactam skeleton and is in accord with conclusions reported for benzolactams, analogues without the pyrrole moiety. This study also describes the synthesis of hew biologically active compounds (26a, 26b, 28) based on inactive (+)-epiindolactam-V (24), involving a further application of the aza-Claisen rearrangement. Bridge formation between positions 5 and 13 of indolactam derivatives represents a particularly effective analogue design strategy, allowing for the remote control of the conformation of this ring system and for the introduction of a wide range of structural variations, as required for the development of new protein kinase C activators with high isozyme selectivity.

  DOI：

  10.1021/ja961727j
• 作为产物：
  描述：

  (-)-14-O-acetyl indolactam V 、 N-甲基甲酰苯胺 在 三氯氧磷 作用下， 以 二氯甲烷 为溶剂， 反应 1.17h， 以4%的产率得到(-)-14-O-acetyl-5-formylindolactam-V
  参考文献：
  名称：

  吲哚生物碱肿瘤启动子telocicins的光不稳定衍生物：合成，生物活性和光亲和标记研究。

  摘要：

  合成了新的对光不稳定的Teleocidin衍生物（Az-A-1，Az-C 7和Az-C 2），并通过与肿瘤促进活性相关的三种体外生物测定法进行了检查。Az-A-1（15）和Az-C 7的两个差向异构体（11a，11b）的活性比电离蛋白的基本结构（-）-吲哚-V-（1）高约10至100倍。通过使用可商购的3 H标记的琥珀酰亚胺基-4-叠氮基苯甲酸酯，可以合成具有超过40Ci / mmol的比活性的3 H标记的探针。[ 3 H] Az-A-1和[ 3 H] Az-C 7的特异性结合对于小鼠表皮微粒部分而言，远程信息素的靶组织在约20nM是可饱和的。使用[ 3 H] Az-A-1在颗粒级分上进行光亲和性标记，支持了最近的假设，即telociocidins 7位的烷基链与邻近受体位点的磷脂相互作用。SDS凝胶电泳的光标记颗粒级分表明存在两种蛋白质（约30和50kD），它们分别由[ 3 H] Az-A-1和[

  DOI：

  10.1016/s0040-4020(01)80236-2