13-phenylacetyl-20-tritylphorbol | 179258-40-3

• 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: 13-phenylacetyl-20-tritylphorbol
• 英文别名: phorbol 13-phenylacetate-20-trityl；[(1S,2S,6R,10S,11R,13S,14R,15R)-1,6,14-trihydroxy-4,12,12,15-tetramethyl-5-oxo-8-(trityloxymethyl)-13-tetracyclo[8.5.0.02,6.011,13]pentadeca-3,8-dienyl] 2-phenylacetate
• CAS: 179258-40-3
• 化学式: C₄₇H₄₈O₇
• 分子量: 724.894
• InChiKey: VEGKPQHFJMZQOB-KQAIHCHCSA-N

物化性质

• 沸点：
  809.6±65.0 °C(Predicted)
• 密度：
  1.31±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.5
• 重原子数：
  54
• 可旋转键数：
  10
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  113
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  13-phenylacetyl-20-tritylphorbol 在 4-二甲氨基吡啶 、 高氯酸 、 四氯化锡 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 反应 6.33h， 生成 佛波醇 12-苯乙酸酯 13-乙酸酯 20-高香草酸酯
  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：

  苯乙酸 、 phorbol 20-trityl 在 4-二甲氨基吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以67%的产率得到13-phenylacetyl-20-tritylphorbol
  参考文献：
  名称：

  佛波二酯和 12-Deoxy-16-hydroxyphorbol 13,16-二酯诱导 TGFα 释放和成年小鼠神经发生

  摘要：

  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。

  DOI：

  10.1021/acs.jmedchem.1c00156

文献信息

• Synthesis and Biological Evaluation of Phorbol-Resiniferatoxin (RTX) Hybrids
  作者：Giovanni Appendino、Andrea Bertolino、Alberto Minassi、Rita Annunziata、Arpad Szallasi、Luciano de Petrocellis、Vincenzo Di Marzo

  DOI：10.1002/ejoc.200400122

  日期：2004.8

  Phorboid 20-homovanillates modified on ring C to mimic the constitution and conformation of the ultrapotent vanilloid resiniferatoxin (RTX) and on the AB ring system to suppress the tumour-promoting potential of the terpenoid core were prepared. Several unexpected reactions were discovered, and the structure-activity relationships for this class of vanilloid ligands were expanded. (© Wiley-VCH Verlag

  制备了在环 C 上修饰的 Phorboid 20-homovanillates 以模拟超强效香草树脂毒素 (RTX) 的构成和构象，并在 AB 环系统上修饰以抑制萜类核心的促肿瘤潜力。发现了几个意想不到的反应，并扩展了此类香草配体的构效关系。(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
• [EN] 12-DEOXYPHORBOL DERIVATIVES AND USES THEREOF<br/>[FR] DÉRIVÉS DE 12-DÉSOXYPHORBOLES ET LEURS UTILISATIONS<br/>[ES] DERIVADOS DE 12-DESOXIFORBOLES Y USOS DE LOS MISMOS
  申请人：[es]UNIVERSIDAD DE CÁDIZ

  公开号：WO2022144482A1

  公开（公告）日：2022-07-07

  Esta invención está relacionada con la síntesis y el empleo de derivados de 12- DESOXIFORBOLES (o esteres de forbol) para favorecer la diferenciación a neuronas de precursores neurales o células madre neurales en cultivo y en cerebro adulto. Adicionalmente, también se relaciona con el empleo del mismo tipo de compuesto para la elaboración de una composición farmacéutica útil en el tratamiento de daños en el sistema nervioso central que cursen con perdida neuronal.