4alpha-佛波醇 | 26241-63-4

• 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
• 中文名称: 4alpha-佛波醇
• 中文别名: ALPHA-佛波醇；4α-佛波醇；N-(2-乙酰氨基)亚氨基二乙酸
• 英文名称: 4α-phorbol
• 英文别名: Isophorbol；(1S,2S,6S,10S,11R,13S,14R,15R)-1,6,13,14-tetrahydroxy-8-(hydroxymethyl)-4,12,12,15-tetramethyltetracyclo[8.5.0.02,6.011,13]pentadeca-3,8-dien-5-one
• CAS: 26241-63-4
• 化学式: C₂₀H₂₈O₆
• 分子量: 364.439
• InChiKey: QGVLYPPODPLXMB-FYYCTCHMSA-N

物化性质

• 物理描述：
  Phorbol is a white solid. (NTP, 1992)
• 颜色/状态：
  Anhydrous crystals; two forms of solvated crystals from ethyl acetate; solvated crystals from methanol or ethanol
• 熔点：
  250-251 °C (decomposition)
• 溶解度：
  Quite soluble (NTP, 1992)
• 密度：
  1.4 g/cu cm (est)
• 蒸汽压力：
  1.1X10-14 mm Hg at 25 °C (est)
• 稳定性/保质期：
  Phorbol is unstable to prolonged exposure to air, light and ambient temperatures.
• 旋光度：
  Specific optical rotation (water): +102 deg at 24 °C/D; +118 deg at 20 °C/D (c = 0.4 in dioxane)
• 分解：
  Decomposes at 250-251 °C (solvent free)
• 解离常数：
  pKa: 12.5 at 25 °C (est)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.8
• 重原子数：
  26
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  118
• 氢给体数：
  5
• 氢受体数：
  6

安全信息

• 危险等级：
  6.1(b)
• 安全说明：
  S26,S27,S36/37/39,S45
• 危险类别码：
  R26/27/28,R36/37/38
• 危险品运输编号：
  UN 2811 6.1/PG 3

反应信息

• 作为反应物：
  描述：

  4alpha-佛波醇 在 4-二甲氨基吡啶 、 TEA 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 1.5h， 生成 13,20-diacetyl-12-phenylacetyl-4α-phorbol
  参考文献：
  名称：

  佛波-树脂毒素 (RTX) 杂种的合成和生物学评价

  摘要：

  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)

  DOI：

  10.1002/ejoc.200400122

文献信息

• Inhibition of Cytopathic Effect of Human Immunodeficiency Virus Type-1 by Various Phorbol Derivatives.
  作者：Sahar El-Mekkawy、Meselhy Ragab Meselhy、Atef Abdel-Monem Abdel-Hafez、Norio Nakamura、Masao Hattori、Takuya Kawahata、Toru Otake

  DOI：10.1248/cpb.50.523

  日期：——

  Forty-eight derivatives of phorbol (9) and isophorbol (14) were evaluated for their inhibition of human immunodeficiency virus (HIV)-1 induced cytopathic effects (CPE) on MT-4 cells, as well as their activation of protein kinase C (PKC), as indices of anti-HIV-1 and tumor promoting activities, respectively. Of these compounds, the most potent inhibition of CPE was observed in 12-O-tetradecanoylphorbol 13-acetate (8) and 12-O-acetylphorbol 13-decanoate (6). The former also showed the strongest PKC activation activity, while the latter showed no activity at 10 ng/ml. Both activities were generally observed in those phorbol derivatives with an A/B trans configuration, but not in the isophorbol derivatives with an A/B cis configuration. Acetylation of 20-OH in the phorbol derivatives significantly reduced the inhibition of CPE, as shown in 12-O-, 20-O-diacetylphorbol 13-decanoate (6a) (IC100=15.6 μg/ml) vs. compound 6 (IC100=0.0076 μg/ml), and 12-O-tetradecanoylphorbol 13,20-diacetate (8a) (IC100=15.6 μg/ml) vs. 12-O-tetradecanoylphorbol 13-acetate (8) (IC100=0.00048 μg/ml), except in the case of 12-O-decanoylphorbol 13-(2-methylbutyrate) (4) and phorbol 12,13-diacetate (9c). The reduction of a carbonyl group at C-3 abruptly reduced the inhibition of CPE, as observed in 3β-hydroxyphorbol 12,13,20-triacetate (9f) (IC100=500 μg/ml) vs. phorbol 12,13,20-triacetate (9d) (IC100=62.5 μg/ml). Although 8 was equipotent in the inhibition of CPE, and activation of PKC, both activities were abruptly decreased by the acetylation of 20-OH and methylation of 4-OH [as in 8a and 4-O-methyl-12-O-tetradecanoylphorbol 13,20-diacetate (8b), respectively]. On the other hand, its positional isomer (12-O-acetylphorbol 13-tetradecanoate (8c) showed neither activities. The removal of a long acyl group in 8 led to a substantial loss of both activities, as shown in phorbol 13-acetate (9b). Of the 12-O-acetyl-13-O-acylphorbol derivatives, the highest inhibition of CPE was observed in 6, which has a dodecanoyl residue at C-13. Both an increase and decrease in the number of fatty acid carbon chains resulted in significant reduction of the inhibition of CPE.

  四十八种分子的phorbol（9）和isophorbol（14）被评估其对人类免疫缺陷病毒（HIV）-1诱导的细胞病变效应（CPE）在MT-4细胞上的抑制作用，以及其激活蛋白激酶C（PKC）的能力，分别作为抗HIV-1和肿瘤促进活性的指标。在这些化合物中，12-O-十四酸酯phorbol 13-醋酸酯（8）和12-O-乙酰phorbol 13-癸酸酯（6）显示出对CPE的最强抑制作用。前者也表现出最强的PKC激活活性，而后者在10 ng/ml时未显示活性。这两种活性通常是在具有A/B反式构型的phorbol衍生物中观察到的，而不是在具有A/B顺式构型的isophorbol衍生物中。对phorbol衍生物中的20-OH进行乙酰化显著降低了对CPE的抑制，正如在12-O-、20-O-二乙酰phorbol 13-癸酸酯（6a）（IC100=15.6 μg/ml）与化合物6（IC100=0.0076 μg/ml）之间的对比，以及在12-O-十四酸酯phorbol 13,20-二乙酸酯（8a）（IC100=15.6 μg/ml）与12-O-十四酸酯phorbol 13-醋酸酯（8）（IC100=0.00048 μg/ml）之间的对比，除了在12-O-癸酸酯phorbol 13-(2-甲基丁酸酯)（4）和phorbol 12,13-二乙酸酯（9c）情况下。C-3碳基团的去除突然降低了对CPE的抑制，正如在3β-羟基phorbol 12,13,20-三乙酸酯（9f）（IC100=500 μg/ml）与phorbol 12,13,20-三乙酸酯（9d）（IC100=62.5 μg/ml）之间的对比所观察到的。尽管8在抑制CPE和激活PKC方面具有同等效力，但20-OH的乙酰化和4-OH的甲基化（如在8a和4-O-甲基-12-O-十四酸酯phorbol 13,20-二乙酸酯（8b）中）都急剧降低了这两种活性。另一方面，其位置异构体（12-O-乙酰phorbol 13-十四酸酯（8c）则表现出两种活性均无）。在8中去除长的酰基团导致这两种活性的显著丧失，如在phorbol 13-醋酸酯（9b）中所示。在12-O-乙酰-13-O-酰基phorbol衍生物中，6显示出对CPE的最高抑制，C-13处具有十二酸酯残基。脂肪酸碳链数量的增加和减少均导致对CPE抑制作用的显著降低。
• Purification of 12-O-tetradecanoylphorbol-13-acetate, phorbol, and 4.alpha.
  申请人：The Board of Trustees of the University of Ill.

  公开号：US04468328A1

  公开（公告）日：1984-08-28

  Droplet counter-current chromatography is utilized to isolate and purify 12-O-tetradecanoylphorbol-13-acetate (TPA), phorbol, and the diastereoisomer 4.alpha.-phorbol from croton oil. The stationary and mobile phases for the procedure are derived from an equilibrated mixture of hexane-diethylether-n-propanol-ethanol-water, the separated upper layer of which comprises the stationary phase and the bottom layer of which the mobile phase. The TPA and the phorbol isomers are obtained in exceptionally high purity by further treatment with liquid column chromatography and thin-layer chromatography.

  利用滴定逆流色谱法从卡波油中分离和纯化十二烷基酯酸酯型13-醋酸酯（TPA）、佛波醇和对映异构体4.alpha.-phorbol。该过程的固定相和流动相来自于已平衡混合物的己烷-乙醚-正丙醇-乙醇-水，其中分离的上层为固定相，下层为流动相。通过进一步的液相色谱和薄层色谱处理，可获得极高纯度的TPA和佛波醇异构体。
• METHOD OF SCREENING BAFF SUPPRESSOR OR INHIBITOR
  申请人：Kowa Co., Ltd.

  公开号：EP1801231A1

  公开（公告）日：2007-06-27

  A method of screening a novel BAFF suppressor or inhibitor. More specifically speaking, a method which comprises adding a combination of TPA with ionomycin and/or an anti-CD3 antibody to a cultured human cell to thereby induce the production of BAFF by the cell; a method of screening a substance capable of suppressing the expression or activity of BAFF which comprises adding a test substance to a BAFF-production system prepared by adding a combination of TPA with ionomycin and/or an anti-CD3 antibody to a cultured human cell and measuring the expression amount and/or the activity of BAFF in the BAFF-production system; and a BAFF production inducer for a BAFF-producing cell which contains a combination of TPA with ionomycin and/or an anti-CD3 antibody.

  一种筛选新型 BAFF 抑制剂或抑制剂的方法。更具体地说，该方法包括向培养的人体细胞中加入 TPA 与离子霉素和/或抗 CD3 抗体的组合，从而诱导细胞产生 BAFF；一种筛选能够抑制 BAFF 表达或活性的物质的方法，该方法包括向通过向培养的人体细胞中加入 TPA 与离子霉素和/或抗-CD3 抗体的组合制备的 BAFF 生产系统中加入试验物质，并测量 BAFF 生产系统中 BAFF 的表达量和/或活性；以及一种 BAFF 生产细胞的 BAFF 生产诱导剂，该诱导剂含有 TPA 与离子霉素和/或抗-CD3 抗体的组合。
• FMO3 inhibitors for treating pain
  申请人：Akron Molecules GmbH

  公开号：EP2674161A1

  公开（公告）日：2013-12-18

  The present invention relates to new therapies to treat pain and related diseases, as well as pharmaceutical compounds for use in said therapies.

  本发明涉及治疗疼痛和相关疾病的新疗法，以及用于上述疗法的药物化合物。
• 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.