phorbol 12-terephthalate-13-acetate-20-trityl | 203261-40-9

• 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: phorbol 12-terephthalate-13-acetate-20-trityl
• CAS: 203261-40-9
• 化学式: C₄₉H₄₈O₁₀
• 分子量: 796.914
• InChiKey: JMRRJBBBRUFBJB-KVNJWRSLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.08
• 重原子数：
  59.0
• 可旋转键数：
  10.0
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  156.66
• 氢给体数：
  3.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  phorbol 12-terephthalate-13-acetate-20-trityl 在 苯甲醚 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 以84%的产率得到phorbol 12-terephthalate-13-acetate
  参考文献：
  名称：

  Protein Kinase C Translocation by Modified Phorbol Esters with Functionalized Lipophilic Regions

  摘要：

  Several novel phorbol esters were prepared with polar functional groups terminating their C12 and/or C13 acyl chains. Designed to be inhibitory protein kinase C (PKC) ligands, these phorbol analogues contain various polar functional groups (amide, ester, carboxylic acid, or quaternary ammonium salt) to prevent membrane insertion of the PKC-phorbol ester complex. All phorbol derivatives were synthesized with use of diterpene starting materials obtained from croton oil, the seed oil of Croton tiglium. The ability of these derivatives to recruit PKC to the lipid bilayer-a usual requirement for enzyme activation-was determined by using a sucrose-loaded vesicle assay. Phorbol 12-octanoate-13-acetate derivatives translocate PKC-betaII to increasing degrees as the functionality on the C12 ester becomes more hydrophobic. Likewise, PKC translocation by carboxylic acid-containing phorbol esters was dependent upon length and saturation of the hydrocarbon tether. The most promising PKC inhibitors had short carboxylic acids capping their C12 and C13 acyl chains, since these compounds did not recruit PKC to any appreciable extent.

  DOI：

  10.1021/jo030029w
• 作为产物：
  描述：

  phorbol 13-acetate 20-tritylether 在 吗啉 、 4-二甲氨基吡啶 、 四(三苯基膦)钯 、 N,N'-二环己基碳二亚胺 作用下， 生成 phorbol 12-terephthalate-13-acetate-20-trityl
  参考文献：
  名称：

  Rational Design, Synthesis, and Evaluation of a New Type of PKC Inhibitor

  摘要：

  DOI：

  10.1021/ja971270t

文献信息

• Dramatic Switching of Protein Kinase C Agonist/Antagonist Activity by Modifying the 12-Ester Side Chain of Phorbol Esters
  作者：Reiko Wada、Yutaka Suto、Motomu Kanai、Masakatsu Shibasaki

  DOI：10.1021/ja027048s

  日期：2002.9.1

  A dramatic switching of PKC agonist and antagonist activity was observed by modification of the hydrophilicity of the 12-ester side chain of phorbol. Thus, phorbol ester 4 that contains a glycol at the 12-ester chain demonstrated a pure and significant antagonist ability of PKC; however, 3 that contains an alkanol at the 12-ester chain demonstrated a potent PKC agonist activity. On the basis of the structural difference between 3 and 4 and results of the partition assay in the Hela cell/PBS buffer system, we propose that 4 acts as a translocation poison of the PKC-phorbol ester complex. The approach of controlling the agonist/antagonist activity of phorbol esters by the nature (i.e., hydrophilicity, charge, and rigidity, etc.) of the 12-ester chain may be very useful for developing selective PKC inhibitors and a potential pharmaceutical compound for anticancer therapies.