pyrrolidine-1,2-dicarboxylic acid (2S)-2-{(1S,3S,5S)-6-[(1S)-3-allyloxycarbonyl-1-[(triphenylmethylthio)methyl]propylcarbamoyl]-1-tert-butyl-3-methyl-5-(2,2,2-trichloroethoxycarbonyloxy)hex-1-yl}ester 1-(9H-fluoren-9-ylmethyl)ester | 1585181-30-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: pyrrolidine-1,2-dicarboxylic acid (2S)-2-{(1S,3S,5S)-6-[(1S)-3-allyloxycarbonyl-1-[(triphenylmethylthio)methyl]propylcarbamoyl]-1-tert-butyl-3-methyl-5-(2,2,2-trichloroethoxycarbonyloxy)hex-1-yl}ester 1-(9H-fluoren-9-ylmethyl)ester
• 英文别名: pyrrolidine-1,2-dicarboxylic acid (2S)-2-{(1S,3S,5S)-6-[(1S)-3-allyloxycarbonyl-1-(triphenylmethylthio)methylpropylcarbamoyl]-1-tert-butyl-3-methyl-5-(2,2,2-trichloroethoxycarbonyloxy)hex-1-yl}-ester 1-(9H-fluoren-9-ylmethyl)ester；1-((9H-fluoren-9-yl)methyl)2-((3S,5S)-9-(((S)-5-(allyloxy)-5-oxo-1-(tritylthio)pentan-2-yl)amino)-2,2,5-trimethyl-9-oxo-7-(((2,2,2-trichloroethoxy)carbonyl)oxy)nonan-3-yl) (2S)-pyrrolidine-1,2-dicarboxylate
• CAS: 1585181-30-1
• 化学式: C₆₂H₆₉Cl₃N₂O₁₀S
• 分子量: 1140.66
• InChiKey: KXNRDHIZDXVZTO-PYELWSQTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  13.78
• 重原子数：
  78.0
• 可旋转键数：
  24.0
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  146.77
• 氢给体数：
  1.0
• 氢受体数：
  11.0

反应信息

• 作为反应物：
  描述：

  pyrrolidine-1,2-dicarboxylic acid (2S)-2-{(1S,3S,5S)-6-[(1S)-3-allyloxycarbonyl-1-[(triphenylmethylthio)methyl]propylcarbamoyl]-1-tert-butyl-3-methyl-5-(2,2,2-trichloroethoxycarbonyloxy)hex-1-yl}ester 1-(9H-fluoren-9-ylmethyl)ester 在 三氟甲磺酸酐 、 三苯基氧化膦 作用下， 反应 0.5h， 生成
  参考文献：
  名称：

  Improved Total Synthesis and Biological Evaluation of Potent Apratoxin S4 Based Anticancer Agents with Differential Stability and Further Enhanced Activity

  摘要：

  Apratoxins are cytotoxic natural products originally isolated from marine cyanobacteria that act by preventing cotranslational translocation early in the secretory pathway to downregulate receptor levels and inhibit growth factor secretion, leading to potent antiproliferative activity. Through rational design and total synthesis of an apratoxin A/ E hybrid, apratoxin S4 (1a), we have previously improved the antitumor activity and tolerability in vivo. Compound la and newly designed analogues apratoxins S7-S9 (1b-d), with various degrees of methylation at C34 (1b,c) or epimeric configuration at C30 (1d), were efficiently synthesized utilizing improved procedures. Optimizations have been applied to the synthesis of key intermediate aldehyde 7 and further include the application of Leighton's silanes and modifications of Kelly's methods to induce thiazoline ring formation in other crucial steps of the apratoxin synthesis. Apratoxin S9 (1d) exhibited increased activity with subnanomolar potency. Apratoxin S8 (lc) lacks the propensity to be deactivated by dehydration and showed efficacy in a human HCT116 xenograft mouse model.

  DOI：

  10.1021/jm4019965
• 作为产物：
  描述：

  tert-butyl (S)-(1-oxo-3-(tritylthio)propan-2-yl)carbamate 在 吡啶 、 2,6-二甲基吡啶 、 4-二甲氨基吡啶 、 sodium tetrahydroborate 、 三氟甲磺酸三甲基硅酯 、 水 、 potassium carbonate 、 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 、 lithium hydroxide 作用下， 以 乙醇 、 二氯甲烷 、 二甲基亚砜 、 甲苯 为溶剂， 反应 45.5h， 生成 pyrrolidine-1,2-dicarboxylic acid (2S)-2-{(1S,3S,5S)-6-[(1S)-3-allyloxycarbonyl-1-[(triphenylmethylthio)methyl]propylcarbamoyl]-1-tert-butyl-3-methyl-5-(2,2,2-trichloroethoxycarbonyloxy)hex-1-yl}ester 1-(9H-fluoren-9-ylmethyl)ester
  参考文献：
  名称：

  [EN] MACROCYCLIC THERAPEUTIC AGENTS, METHODS OF MANUFACTURE, AND METHODS OF TREATMENT
  [FR] AGENTS THÉRAPEUTIQUES MACROCYCLIQUES, DES MÉTHODES DE FABRICATION, ET MÉTHODES DE TRAITEMENT

  摘要：

  本发明描述了具有治疗活性的大环化合物，以及治疗自身免疫疾病、炎症、癌症、肿瘤和与细胞增殖有关的疾病的机制和方法。

  公开号：

  WO2015127161A1

文献信息

• Total Synthesis and Biological Evaluation of Apratoxin E and Its C30 Epimer: Configurational Reassignment of the Natural Product
  作者：Ping Wu、Weijing Cai、Qi-Yin Chen、Senhan Xu、Ruwen Yin、Yingxia Li、Wei Zhang、Hendrik Luesch

  DOI：10.1021/acs.orglett.6b02780

  日期：2016.10.21

  preclinical development. Through total synthesis using two different strategies, it was determined that the originally proposed configuration of the thiazoline at C30 is opposite from that in apratoxin A, in contrast to previous assumptions on biosynthetic grounds. The epimer and true natural apratoxin E were synthesized, and the biological activities were evaluated.

  Apratoxin E为在临床前开发中设计Aprato毒素A / E杂种提供了灵感。通过使用两种不同策略的全合成，可以确定最初提出的C30噻唑啉构型与Apratoxin A中的构型相反，这与以前基于生物合成的假设相反。合成了差向异构体和真正的天然阿普毒素E，并评估了其生物学活性。