[(1R,2S,6R,10S,11R,13S,15S)-1,6-dihydroxy-8-(hydroxymethyl)-4,12,12,15-tetramethyl-5,14-dioxo-13-tetracyclo[8.5.0.02,6.011,13]pentadeca-3,8-dienyl] 2-phenylacetate | 179258-45-8

• 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: [(1R,2S,6R,10S,11R,13S,15S)-1,6-dihydroxy-8-(hydroxymethyl)-4,12,12,15-tetramethyl-5,14-dioxo-13-tetracyclo[8.5.0.02,6.011,13]pentadeca-3,8-dienyl] 2-phenylacetate
• CAS: 179258-45-8
• 化学式: C₂₈H₃₂O₇
• 分子量: 480.558
• InChiKey: MFRXNGHORNAKJZ-KBZKMASWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  35
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  121
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  [(1R,2S,6R,10S,11R,13S,15S)-1,6-dihydroxy-8-(hydroxymethyl)-4,12,12,15-tetramethyl-5,14-dioxo-13-tetracyclo[8.5.0.02,6.011,13]pentadeca-3,8-dienyl] 2-phenylacetate 在 4-二甲氨基吡啶 、 四氯化锡 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 2.5h， 生成 [(1R,2S,6R,10S,11R,13S,15S)-1,6-dihydroxy-8-[[2-(4-hydroxy-3-methoxyphenyl)acetyl]oxymethyl]-4,12,12,15-tetramethyl-5,14-dioxo-13-tetracyclo[8.5.0.02,6.011,13]pentadeca-3,8-dienyl] 2-phenylacetate
  参考文献：
  名称：

  Synthesis and Evaluation of Phorboid 20-Homovanillates:  Discovery of a Class of Ligands Binding to the Vanilloid (Capsaicin) Receptor with Different Degrees of Cooperativity

  摘要：

  A number of phorboid 20-homovanillates were prepared by condensation of phorbol 12,13-diesters and 12-dehydrophorbol 13-esters with Mem-homovanillic acid followed by removal of the protecting group with SnCl4 in THF. These compounds were evaluated for their ability to inhibit [H-3]resiniferatoxin (RTX) binding to rat spinal cord membranes. Compounds bearing a lipophilic ester group on ring C were considerably active, but a surprising tolerance of the vanilloid receptor toward the location and the orientation of this ester group was disclosed. Unexpectedly, these ligands could also diminish, to a variable degree, the positive cooperativity which characterizes RTX binding to the vanilloid receptor. Phorbol 12-phenylacetate 13-acetate 20-homovanillate (PPAHV, 6a), a compound which abolished binding cooperativity, was further tested in a variety of in vivo assays used to characterize vanilloid-like activity. PPAHV showed only a marginal pungency and failed to induce a measurable hypothermia response at doses (up to 200 mg/kg) at which it effectively desensitized against neurogenic inflammation. These data suggest that the peculiar binding behavior of these ligands might be associated with a distinct spectrum of biological activity.

  DOI：

  10.1021/jm960063l
• 作为产物：
  描述：

  phorbol 20-trityl 在 4-二甲氨基吡啶 、 高氯酸 、 4 A molecular sieve 、 N,N'-二环己基碳二亚胺 、 pyridinium chlorochromate 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 4.33h， 生成 [(1R,2S,6R,10S,11R,13S,15S)-1,6-dihydroxy-8-(hydroxymethyl)-4,12,12,15-tetramethyl-5,14-dioxo-13-tetracyclo[8.5.0.02,6.011,13]pentadeca-3,8-dienyl] 2-phenylacetate
  参考文献：
  名称：

  Synthesis and Evaluation of Phorboid 20-Homovanillates:  Discovery of a Class of Ligands Binding to the Vanilloid (Capsaicin) Receptor with Different Degrees of Cooperativity

  摘要：

  A number of phorboid 20-homovanillates were prepared by condensation of phorbol 12,13-diesters and 12-dehydrophorbol 13-esters with Mem-homovanillic acid followed by removal of the protecting group with SnCl4 in THF. These compounds were evaluated for their ability to inhibit [H-3]resiniferatoxin (RTX) binding to rat spinal cord membranes. Compounds bearing a lipophilic ester group on ring C were considerably active, but a surprising tolerance of the vanilloid receptor toward the location and the orientation of this ester group was disclosed. Unexpectedly, these ligands could also diminish, to a variable degree, the positive cooperativity which characterizes RTX binding to the vanilloid receptor. Phorbol 12-phenylacetate 13-acetate 20-homovanillate (PPAHV, 6a), a compound which abolished binding cooperativity, was further tested in a variety of in vivo assays used to characterize vanilloid-like activity. PPAHV showed only a marginal pungency and failed to induce a measurable hypothermia response at doses (up to 200 mg/kg) at which it effectively desensitized against neurogenic inflammation. These data suggest that the peculiar binding behavior of these ligands might be associated with a distinct spectrum of biological activity.

  DOI：

  10.1021/jm960063l