α-tocopheramine succinate | 832082-19-6

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: α-tocopheramine succinate
• 英文别名: α-tocopheryl succinamide；4-oxo-4-[[(2R)-2,5,7,8-tetramethyl-2-[(4R,8R)-4,8,12-trimethyltridecyl]-3,4-dihydrochromen-6-yl]amino]butanoic acid
• CAS: 832082-19-6
• 化学式: C₃₃H₅₅NO₄
• 分子量: 529.804
• InChiKey: UJFHUEFTCMRMOG-NJQVLOCASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.7
• 重原子数：
  38
• 可旋转键数：
  16
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.76
• 拓扑面积：
  75.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  丁二酸酐 、 α-tocopheramine 以 吡啶 为溶剂， 生成 α-tocopheramine succinate
  参考文献：
  名称：

  A novel synthesis of tocopheryl amines and amides

  摘要：

  We report the synthesis of tocopheryl amines and amides from commercially available tocopherols. This synthesis improves the yield and diastereomeric purity of these biologically important compounds. The tocopheryl amines were prepared from the corresponding alpha- and delta-tocopherols using two distinct synthetic routes. The introduction of the C(6)-amino group can be achieved by aryl nitration/reduction or by Pd-catalyzed Substitution of an aryl triflate, depending on the structure of the starting material. We also prepared the succinamide and maleamide derivatives of each amine. Tocopheryl amides are more potent pro-apoptotic anti-cancer agents than the corresponding alpha-tocopheryl esters. These compounds act selectively within the mitochondria of cancer cells. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2008.10.056

文献信息

• Tocopheramine succinate and tocopheryl succinate: Mechanism of mitochondrial inhibition and superoxide radical production
  作者：Julia Gruber、Katrin Staniek、Christopher Krewenka、Rudolf Moldzio、Anjan Patel、Stefan Böhmdorfer、Thomas Rosenau、Lars Gille

  DOI：10.1016/j.bmc.2013.12.036

  日期：2014.1

  Tocopherols (TOH) are lipophilic antioxidants which require the phenolic OH group for their redox activity. In contrast, non-redox active esters of alpha-TOH with succinate (alpha-TOS) were shown to possess proapoptotic activity in cancer cells. It was suggested that this activity is mediated via mitochondrial inhibition with subsequent O-2(center dot-) production triggering apoptosis and that the modification of the linker between the succinate and the lipophilic chroman may modulate this activity. However, the specific mechanism and the influence of the linker are not clear yet on the level of the mitochondrial respiratory chain. Therefore, this study systematically compared the effects of alpha-TOH acetate (alpha-TOA), alpha-TOS and alpha-tocopheramine succinate (alpha-TNS) in cells and submitochondrial particles (SMP). The results showed that not all cancer cell lines are highly sensitive to alpha-TOS and alpha-TNS. In HeLa cells alpha-TNS did more effectively reduce cell viability than alpha-TOS. The complex I activity of SMP was little affected by alpha-TNS and alpha-TOS while the complex II activity was much more inhibited (IC50 = 42 +/- 8 mu M alpha-TOS, 106 +/- 8 mu M alpha-TNS, respectively) than by alpha-TOA (IC50 > 1000 mu M). Also the complex III activity was inhibited by alpha-TNS (IC50 = 137 +/- 6 lM) and alpha-TOS (IC50 = 315 +/- 23 lM). Oxygen consumption of NADH-or succinate-respiring SMP, involving the whole electron transfer machinery, was dose-dependently decreased by alpha-TOS and alpha-TNS, but only marginal effects were observed in the presence of alpha-TOA. In contrast to the similar inhibition pattern of alpha-TOS and alpha-TNS, only alpha-TOS triggered O-2 center dot- 2 formation in succinate- and NADH-respiring SMP. Inhibitor studies excluded complex I as O-2(center dot-) 2 source and suggested an involvement of complex III in O-2(center dot-) 2 production. In cancer cells only alpha-TOS was reproducibly able to increase O-2(center dot-) 2 levels above the background level but neither alpha-TNS nor alpha-TOA. Furthermore, the stability of alpha-TNS in liver homogenates was significantly lower than that of alpha-TOS. In conclusion, this suggests that alpha-TNS although it has a structure similar to alpha-TOS is not acting via the same mechanism and that for alpha-TOS not only complex II but also complex III interactions are involved. (C) 2013 Elsevier Ltd. All rights reserved.
• Liposomal Formulations of Tocopheryl Amides
  申请人：Salvatore Brian A

  公开号：US20100260830A1

  公开（公告）日：2010-10-14

  Formulations of N-chroman dicarboxylic acid derivatives and their bioisosteres in liposomal systems. Lyophilized liposomal dosage forms of N-chromans, are found to be stable, to achieve therapeutically meaningful plasma levels on administration to a mammalian host, and to demonstrate selective pro-apoptotic oncolytic properties in vivo. Advantageously, these formulations overcome the systemic toxicity that characterized their administration by other dosage forms.
• A novel synthesis of tocopheryl amines and amides
  作者：Elahe Mahdavian、Smink Sangsura、Geoffrey Landry、John Eytina、Brian A. Salvatore

  DOI：10.1016/j.tetlet.2008.10.056

  日期：2009.1

  We report the synthesis of tocopheryl amines and amides from commercially available tocopherols. This synthesis improves the yield and diastereomeric purity of these biologically important compounds. The tocopheryl amines were prepared from the corresponding alpha- and delta-tocopherols using two distinct synthetic routes. The introduction of the C(6)-amino group can be achieved by aryl nitration/reduction or by Pd-catalyzed Substitution of an aryl triflate, depending on the structure of the starting material. We also prepared the succinamide and maleamide derivatives of each amine. Tocopheryl amides are more potent pro-apoptotic anti-cancer agents than the corresponding alpha-tocopheryl esters. These compounds act selectively within the mitochondria of cancer cells. (C) 2008 Elsevier Ltd. All rights reserved.