4alpha-Phorbol 13-decanoate | 1152521-97-5

• 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: 4alpha-Phorbol 13-decanoate
• 英文别名: 4α-phorbol 13-decanoate；[(1S,2S,6S,10S,11R,13S,14R,15R)-1,6,14-trihydroxy-8-(hydroxymethyl)-4,12,12,15-tetramethyl-5-oxo-13-tetracyclo[8.5.0.02,6.011,13]pentadeca-3,8-dienyl] decanoate
• CAS: 1152521-97-5
• 化学式: C₃₀H₄₆O₇
• 分子量: 518.691
• InChiKey: YJFFPVQHOKPCRV-JQRZRIHSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  37
• 可旋转键数：
  11
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  124
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  [(1S,2S,6S,10S,11R,13S,14R,15R)-13-decanoyloxy-1,6,14-trihydroxy-4,12,12,15-tetramethyl-5-oxo-8-tetracyclo[8.5.0.02,6.011,13]pentadeca-3,8-dienyl]methyl decanoate 在 高氯酸 作用下， 以 甲醇 为溶剂， 以48 mg的产率得到4alpha-Phorbol 13-decanoate
  参考文献：
  名称：

  Modulation of the Transient Receptor Potential Vanilloid Channel TRPV4 by 4α-Phorbol Esters: A Structure−Activity Study

  摘要：

  The mechanism of activation of the transient receptor potential vanilloid 4 (TRPV4) channel by 4 alpha-phorbol esters was investigated by combining information from chemical modification of 4 alpha-phorbol-didecanoate (4 alpha-PDD, 2a), site-directed mutagenesis, Ca2+ imaging, and electrophysiology. Binding of 4 alpha-phorbol esters occurs in a loop in the TM3-TM4 domain of TRPV4 that is analogous to the capsaicin binding site of TRPV1, and the ester decoration of ring C and the A,B ring junction are critical for activity. The lipophilic ester groups on ring C serve mainly as a steering element, affecting the orientation of the diterpenoid core into the ligand binding pocket, while the nature of the A,B ring junction plays an essential role in the Ca2+-dependence of the TRPV4 response. Taken together, our results show that 4 alpha-phorbol is a useful template to investigate the molecular details of TRPV4 activation by small molecules and obtain information for the rational design of structurally simpler ligands for this ion channel.

  DOI：

  10.1021/jm9001007

文献信息

• Modulation of the Transient Receptor Potential Vanilloid Channel TRPV4 by 4α-Phorbol Esters: A Structure−Activity Study
  作者：Thomas Kjær Klausen、Alberto Pagani、Alberto Minassi、Abdellah Ech-Chahad、Jean Prenen、Grzegorz Owsianik、Else Kay Hoffmann、Stine Falsig Pedersen、Giovanni Appendino、Bernd Nilius

  DOI：10.1021/jm9001007

  日期：2009.5.14

  The mechanism of activation of the transient receptor potential vanilloid 4 (TRPV4) channel by 4 alpha-phorbol esters was investigated by combining information from chemical modification of 4 alpha-phorbol-didecanoate (4 alpha-PDD, 2a), site-directed mutagenesis, Ca2+ imaging, and electrophysiology. Binding of 4 alpha-phorbol esters occurs in a loop in the TM3-TM4 domain of TRPV4 that is analogous to the capsaicin binding site of TRPV1, and the ester decoration of ring C and the A,B ring junction are critical for activity. The lipophilic ester groups on ring C serve mainly as a steering element, affecting the orientation of the diterpenoid core into the ligand binding pocket, while the nature of the A,B ring junction plays an essential role in the Ca2+-dependence of the TRPV4 response. Taken together, our results show that 4 alpha-phorbol is a useful template to investigate the molecular details of TRPV4 activation by small molecules and obtain information for the rational design of structurally simpler ligands for this ion channel.