N-phthaloyl-1-(3,3-dimethylallyl)-L-tryptophane methylester | 287100-53-2

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: N-phthaloyl-1-(3,3-dimethylallyl)-L-tryptophane methylester
• 英文别名: N^a-(3,3-dimethylallyl)-N^b-phthaloyl-L-tryptophan methyl ester；methyl (2S)-2-(1,3-dioxoisoindol-2-yl)-3-[1-(3-methylbut-2-enyl)indol-3-yl]propanoate
• CAS: 287100-53-2
• 化学式: C₂₅H₂₄N₂O₄
• 分子量: 416.477
• InChiKey: NSUDZFOECPQABG-QFIPXVFZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  31
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  68.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-phthaloyl-1-(3,3-dimethylallyl)-L-tryptophane methylester 在 三氟化硼乙醚 作用下， 以 二氯甲烷 为溶剂， 反应 18.0h， 以61%的产率得到methyl N-phthaloyl-2-(3-methyl-2-butenyl)-L-tryptophan
  参考文献：
  名称：

  Studies in the aza-Cope reaction: a formal highly enantioselective synthesis of tryprostatin B

  摘要：

  DOI：

  10.1016/s0040-4039(00)00455-x
• 作为产物：
  描述：

  Sodium; (S)-2-amino-3-[1-(3-methyl-but-2-enyl)-1H-indol-3-yl]-propionate 生成 N-phthaloyl-1-(3,3-dimethylallyl)-L-tryptophane methylester
  参考文献：
  名称：

  Studies in the aza-Cope reaction: a formal highly enantioselective synthesis of tryprostatin B

  摘要：

  DOI：

  10.1016/s0040-4039(00)00455-x

文献信息

• Studies in sigmatropic rearrangements of N-prenylindole derivatives ? a formal enantiomerically pure synthesis of tryprostatin B
  作者：A. Sofia P. Cardoso、M. Manuel B. Marques、Natarajan Srinivasan、Sundaresan Prabhakar、Ana M. Lobo、Henry S. Rzepa

  DOI：10.1039/b606457d

  日期：——

  Rearrangement of Na-prenyl-Nb-acetyltryptamine, induced by BF3·Et2O at low temperature, leads to a 2-prenyl derivative, and thence to the tricyclic tryptamine 7 and the indoline 8. Similarly, Na-prenyl-Nb-phthaloyl-L-tryptophan methyl ester furnished the corresponding 2-prenyl derivative 16, a known advanced precursor of tryprostatin B. Density functional (B3LYP) calculations for the putative rearrangement transition state for N-prenylskatole show that prior coordination of BF3 to the indolic nitrogen changes the character of the subsequent sigmatropic pericyclic shifts from being entirely covalent to acquiring a significant degree of ionic character. The shifting prenyl group favours the endo over the exo mode of the transition state by 4.1 kcal mol−1.

  Na-异戊二烯基-Nb-乙酰色胺在低温下由BF3·Et2O诱导发生重排，生成2-异戊二烯基衍生物，进而生成三环色胺7和二氢吲哚8。类似地，Na-异戊二烯基-Nb-邻苯二甲酰基-L -色氨酸甲酯提供了相应的 2-异戊二烯基衍生物 16，这是一种已知的胰前列腺素 B 的高级前体。 N-异戊烯基粪臭素推定重排过渡态的密度泛函 (B3LYP) 计算表明， 与吲哚氮的事先配位改变了特性随后的σ周环从完全共价转变为获得显着程度的离子特征。移动的异戊二烯基团有利于过渡态的内型模式，而不是外型模式，高出 4.1 kcal mol·1。
• Development of Mithramycin Analogues with Increased Selectivity toward ETS Transcription Factor Expressing Cancers
  作者：Prithiba Mitra、Joseph M. Eckenrode、Abhisek Mandal、Amit K. Jha、Shaimaa M. Salem、Markos Leggas、Jürgen Rohr

  DOI：10.1021/acs.jmedchem.8b01107

  日期：2018.9.13

  Mithramycin A (1) was identified as the top potential inhibitor of the aberrant ETS transcription factor EWSFLI1, which causes Ewing sarcoma. Unfortunately, 1 has a narrow therapeutic window, compelling us to seek less toxic and more selective analogues. Here, we used MTMSA (2) to generate analogues via peptide coupling and fragment-based drug development strategies. Cytotoxicity assays in ETS and non-ETS dependent cell lines identified two dipeptide analogues, 60 and 61, with 19.1- and 15.6-fold selectivity, respectively, compared to 1.5-fold for 1. Importantly, the cytotoxicity of 60 and 61 is <100 nM in ETS cells. Molecular assays demonstrated the inhibitory capacity of these analogues against EWS-FLI1 mediated transcription in Ewing sarcoma. Structural analysis shows that positioning the tryptophan residue in a distal position improves selectivity, presumably via interaction with the ETS transcription factor. Thus, these analogues may present new ways to target transcription factors for clinical use.