phorbol 12,13-di(phenylacetate)-20-trityl | 179258-28-7

• 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 12,13-di(phenylacetate)-20-trityl
• 英文别名: [(1S,2S,6R,10S,11R,13S,14R,15R)-1,6-dihydroxy-4,12,12,15-tetramethyl-5-oxo-13-(2-phenylacetyl)oxy-8-(trityloxymethyl)-14-tetracyclo[8.5.0.02,6.011,13]pentadeca-3,8-dienyl] 2-phenylacetate
• CAS: 179258-28-7
• 化学式: C₅₅H₅₄O₈
• 分子量: 843.029
• InChiKey: RCICBHQJYKKTAB-OHLUBAQFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.7
• 重原子数：
  63
• 可旋转键数：
  14
• 环数：
  9.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  119
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  phorbol 12,13-di(phenylacetate)-20-trityl 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 1.83h， 生成 [(1S,2S,6R,10S,11R,13S,14R,15R)-1,6-dihydroxy-8-[[2-[3-methoxy-4-(2-methoxyethoxymethoxy)phenyl]acetyl]oxymethyl]-4,12,12,15-tetramethyl-5-oxo-13-(2-phenylacetyl)oxy-14-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 、 苯乙酰氯 在 吡啶 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 以90%的产率得到phorbol 12,13-di(phenylacetate)-20-trityl
  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

• Phorbol Diesters and 12-Deoxy-16-hydroxyphorbol 13,16-Diesters Induce TGFα Release and Adult Mouse Neurogenesis
  作者：Abdellah Ezzanad、Ricardo Gómez-Oliva、Felipe Escobar-Montaño、Mónica Díez-Salguero、Noelia Geribaldi-Doldan、Samuel Dominguez-Garcia、José Manuel Botubol-Ares、Carolina de los Reyes、Rosa Durán-Patrón、Pedro Nunez-Abades、Antonio J. Macías-Sánchez、Carmen Castro、Rosario Hernández-Galán

  DOI：10.1021/acs.jmedchem.1c00156

  日期：2021.5.13

  The ability of natural and synthetic compounds to stimulate transforming growth factor alpha (TFGα) release, to increase neural progenitor cell proliferation, and to stimulate neurogenesis was evaluated. All compounds that facilitated TGFα release promoted neural progenitor cell proliferation. The presence of two acyloxy moieties on the tigliane skeleton led to higher levels of activity, which decreased

  制备了带有低亲脂性酯链的佛波醇 12,13-二酯的小型文库，作为成人大脑中潜在的神经源性药物。它们还用于大戟胶乳的靶向 UHPLC-HRMS 筛选. 分离出两种新的 12-deoxy-16-hydroxyphorbol 13,16-二酯，并使用二维 NMR 光谱和 NOE 实验推断了它们的结构。评估了天然和合成化合物刺激转化生长因子 α (TFGα) 释放、增加神经祖细胞增殖和刺激神经发生的能力。所有促进 TGFα 释放的化合物都促进了神经祖细胞的增殖。tigliane 骨架上两个酰氧基部分的存在导致更高水平的活性，当游离羟基位于 C-12 时，活性水平降低。值得注意的是，带有异丁酰氧基的化合物在 TGFα 测定和体外诱导神经祖细胞增殖方面最有效，也导致体内神经发生增强当对小鼠鼻内给药时。