[(1S,2S,6R,10S,11R,13S,14R,15R)-13-acetyloxy-1,6-dihydroxy-8-(hydroxymethyl)-4,12,12,15-tetramethyl-5-oxo-14-tetracyclo[8.5.0.02,6.011,13]pentadeca-3,8-dienyl] 2-(4-azidophenyl)acetate | 179258-41-4

• 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: [(1S,2S,6R,10S,11R,13S,14R,15R)-13-acetyloxy-1,6-dihydroxy-8-(hydroxymethyl)-4,12,12,15-tetramethyl-5-oxo-14-tetracyclo[8.5.0.02,6.011,13]pentadeca-3,8-dienyl] 2-(4-azidophenyl)acetate
• CAS: 179258-41-4
• 化学式: C₃₀H₃₅N₃O₈
• 分子量: 565.623
• InChiKey: LOCQSPRIKCNREW-VTUHWMGDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  41
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  145
• 氢给体数：
  3
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  [(1S,2S,6R,10S,11R,13S,14R,15R)-13-acetyloxy-1,6-dihydroxy-8-(hydroxymethyl)-4,12,12,15-tetramethyl-5-oxo-14-tetracyclo[8.5.0.02,6.011,13]pentadeca-3,8-dienyl] 2-(4-azidophenyl)acetate 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 [(1S,2S,6R,10S,11R,13S,14R,15R)-13-acetyloxy-1,6-dihydroxy-8-[[2-(4-hydroxy-3-methoxyphenyl)acetyl]oxymethyl]-4,12,12,15-tetramethyl-5-oxo-14-tetracyclo[8.5.0.02,6.011,13]pentadeca-3,8-dienyl] 2-(4-azidophenyl)acetate
  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 13-acetate 20-tritylether 在 4-二甲氨基吡啶 、 高氯酸 、 N,N'-二环己基碳二亚胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 2.33h， 生成 [(1S,2S,6R,10S,11R,13S,14R,15R)-13-acetyloxy-1,6-dihydroxy-8-(hydroxymethyl)-4,12,12,15-tetramethyl-5-oxo-14-tetracyclo[8.5.0.02,6.011,13]pentadeca-3,8-dienyl] 2-(4-azidophenyl)acetate
  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

文献信息

• Salt taste modification
  申请人：DeSimone A. John

  公开号：US20050031717A1

  公开（公告）日：2005-02-10

  The pharmacology of the capsaicin receptor has been discovered to be predictive of the enhancement of the non-specific salt taste channel. Salt taste in a mammal may be modified by introducing to a mammalian taste receptor cell, a non-salty ligand which is a taste modulator. Examples of the ligand include capsaicin; resiniferatoxin (RTX); piperine; 2-(3,4-dimethylbenzyl)-3-[(4-hydroxy-3-methoxybenzyl)amino]carbothioyl}propyl pivalate (agonist 23); olvanil, capsiate; evodiamine; ethanol; cetylpyridinium chloride; dodecylpyridinium bromide; capsazepin; SB366791, etc. Salt taste thus may be modified by a non-salty ligand. By introducing certain non-salty ligands into the salt transduction process, the cation non-specific salt taste transduction process may be modified.

  人们发现，辣椒素受体的药理学可以预测非特异性盐味通道的增强。哺乳动物的盐味可以通过向哺乳动物味觉受体细胞引入一种非咸味配体来改变，这种配体是一种味觉调节剂。配体的例子包括辣椒素、树脂松香霉素（RTX）、胡椒碱、2-(3,4-二甲基苄基)-3-[(4-羟基-3-甲氧基苄基)氨基]碳硫酰基}丙基特戊酸酯（激动剂 23）、奥尔万尼尔、辣椒碱、依伏二胺、乙醇、十六烷基氯化吡啶、十二烷基溴化吡啶、辣椒平、SB366791 等。因此，盐味可以通过非咸味配体来改变。通过在盐味转导过程中引入某些非咸味配体，可以改变阳离子非特异性盐味转导过程。
• [EN] SALT TASTE MODIFICATION<br/>[FR] MODIFICATION DU GOUT DE SEL
  申请人：UNIV VIRGINIA COMMONWEALTH

  公开号：WO2005006881A2

  公开（公告）日：2005-01-27

  The pharmacology of the capsaicin receptor has been discovered to be predictive of the enhancement of the non-specific salt taste channel. Salt taste in a mammal may be modified by introducing to a mammalian taste receptor cell, a non-salty ligand which is a taste modulator. Examples of the ligand include capsaicin; resiniferatoxin (RTX); piperine; 2-(3,4-dimethylbenzyl)-3-[(4-hydroxy-3- methoxybenzyl)amino]carbothioyl}propyl pivalate (agonist 23); olvanil, capsiate; evodiamine; ethanol; cetylpyridinium chloride; dodecylpyridinium bromide; capsazepin; SB366791, etc. Salt taste thus may be modified by a non-salty ligand. By introducing certain non-salty ligands into the salt transduction process, the cation non-specific salt taste transduction process may be modified.