Phorbol-12,13,20-tribenzoate | 19891-06-6

• 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-12,13,20-tribenzoate
• 英文别名: Phorbol-11.12.17-tribenzoat；Phorbol-12,13,20-tribenzoat；12β,13,20-tris-benzoyloxy-4,9-dihydroxy-tiglia-1,6-dien-3-one；12β,13,20-Tris-benzoyloxy-4,9-dihydroxy-tiglia-1,6-dien-3-on；[(1S,2S,6R,10S,11R,13S,14R,15R)-13,14-dibenzoyloxy-1,6-dihydroxy-4,12,12,15-tetramethyl-5-oxo-8-tetracyclo[8.5.0.02,6.011,13]pentadeca-3,8-dienyl]methyl benzoate
• CAS: 19891-06-6
• 化学式: C₄₁H₄₀O₉
• 分子量: 676.763
• InChiKey: YSJZBPHREWPDDB-ICDWYKRZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.9
• 重原子数：
  50
• 可旋转键数：
  10
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  136
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  Phorbol-12,13,20-tribenzoate 在 sodium methylate 作用下， 以 甲醇 为溶剂， 生成 佛波醇-12,13-二苯甲酸酯
  参考文献：
  名称：

  Polybenzoate und -acetate des Phorbols und Phorbol-3-ols und funktionelle Derivate der Allylgruppierung des Phorbols

  摘要：

  苯丙二酸酯的碱催化转酯化反应可得到苯丙二酸酯。苯丙五酸酯的碱催化转酯化反应可得到苯丙-9,12,13-三乙酸酯。这可以重新乙酰化以得到苯丙-9,12,13,20-四乙酸酯，该化合物也可以通过苯丙-12,13,20-三乙酸酯与乙酸酐/对甲苯磺酸的处理获得。 用LiAlH4还原苯丙-12,13,20-三乙酸酯可得到苯丙-3-醇，该化合物可还原费林试剂和托伦试剂。仅还原3-酮基团可使用硼氢化钠完成。在所有研究的苯丙酯中，仅在苯丙五酸酯中观察到钠硼氢化物还原过程中的乙酰迁移，导致苯丙-3-醇-3,9,12,13,20-五乙酸酯的形成。通过这些发现，苯丙醇中未被乙酸酐/吡啶在室温下乙酰化的两个三级羟基进一步被表征。 用活性二氧化锰氧化苯丙-12,13-二乙酸酯可得到苯丙-20-醛-12,13-二乙酸酯。通过评估该醛及其某些衍生物、苯丙-12,13-二乙酸酯的环氧化物以及6-氧代-7-羟基-和6,7-二乙酰氧基-20-去甲基苯丙-12,13-二乙酸酯的nmr光谱，进一步表征了苯丙烯醇羟基周围的C原子序列。

  DOI：

  10.1515/znb-1968-1106
• 作为产物：
  描述：

  4beta,9alpha,12beta,13alpha,20-五羟基惕各-1,6-二烯-3-酮 、 苯甲酰氯 在 吡啶 作用下， 生成 Phorbol-12,13,20-tribenzoate
  参考文献：
  名称：

  巴豆油共致癌物二萜母体佛波醇的化学和结构

  摘要：

  讨论了一种含有反应性羟基环丙基甲醇体系的新型四环二萜佛波醇的结构和立体化学。它会在12个羟基的烯丙基上进行质子化反应，得到crotophorbolone（异丙烯基环己酮）和crotophorbolone K（二甲基环丁酮）。与三氟化硼-乙酸一起，佛波三乙酸酯得到乙酰氧基-异丙基环己酮，然后用氢化铝锂-氯化铝处理，然后重新乙酰化，生成乙酸巴豆酚酮乙酸酯的烯醇乙酸酯。这些反应似乎是在12位阳离子形成的结果。

  DOI：

  10.1039/j39680001347

文献信息

• Chemistry and structure of phorbol, the diterpene parent of the co-carcinogens of croton oil
  作者：L. Crombie、M. L. Games、D. J. Pointer

  DOI：10.1039/j39680001347

  日期：——

  The structure and stereochemistry of phorbol, a novel tetracyclic diterpene containing a reactive hydroxycyclopropyl carbinol system, is discussed. It undergoes protonation at the homoallylic 12-hydroxy-group and gives crotophorbolone (an isopropenyl cyclohexanone) and crotophorbolone K (a dimethyl cyclobutanone). With boron trifluoride–acetic acid, phorbol triacetate gives an acetoxy-isopropyl cyclohexanone

  讨论了一种含有反应性羟基环丙基甲醇体系的新型四环二萜佛波醇的结构和立体化学。它会在12个羟基的烯丙基上进行质子化反应，得到crotophorbolone（异丙烯基环己酮）和crotophorbolone K（二甲基环丁酮）。与三氟化硼-乙酸一起，佛波三乙酸酯得到乙酰氧基-异丙基环己酮，然后用氢化铝锂-氯化铝处理，然后重新乙酰化，生成乙酸巴豆酚酮乙酸酯的烯醇乙酸酯。这些反应似乎是在12位阳离子形成的结果。
• Kauffmann; Neumann, Chemische Berichte, 1959, vol. 92, p. 1715,1724
  作者：Kauffmann、Neumann

  DOI：——

  日期：——
• Hecker et al., Zeitschrift fur Naturforschung, 1966, vol. 21 b, p. 1204,1210, 1213
  作者：Hecker et al.

  DOI：——

  日期：——
• 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。
• Polybenzoate und -acetate des Phorbols und Phorbol-3-ols und funktionelle Derivate der Allylgruppierung des Phorbols
  作者：Hans Ulrich Schairer、Heinz Walter Thielmann、Michael Gschwendt、Gert Kreibich、Rainer Schmidt、Erich Hecker

  DOI：10.1515/znb-1968-1106

  日期：1968.11.1

  Base catalysed transesterification of phorbol-12,13,20-tribenzoate yields phorbol-12,13-dibenzoate. By base catalysed transesterification of phorbol-pentaacetate phorbol-9,12,13-triacetate is obtained. This can be re-acetylated to give phorbol-9,12,13,20-tetraacetate which is also obtained by treatment of phorbol-12,13,20-triacetate with acetic anhydride/p-toluene-sulfonic acid.

  Reduction of phorbol-12,13,20-triacetate with LiAlH₄ yields phorbol-3-ol which reduces Fehling's and Tollen's reagent. Reduction of the 3-keto group alone can be accomplished with sodium borohydride. From all phorbol-esters investigated only in phorbol-pentaacetate an acetyl migration is observed during the sodium borohydride reduction leading to phorbol-3-ol-3,9,12,13,20-pentaacetate. By these findings those two tertiary hydroxyl groups of phorbol which are not acetylated with acetic anhydride/pyridine at room temperature were further characterized.

  Oxidation of phorbol-12,13-diacetate with activated manganese dioxide yields phorbol-20-al-12,13-diacetate. By evaluation of nmr-spectra of this aldehyde and of some of its derivatives as well as of the epoxide of phorbol-12,13-diacetate and of 6-oxo-7-hydroxy- and 6,7-diacetoxy-20-nor-phorbol-12,13-diacetate the sequence of C-atoms around the allylic alcohol group of phorbol is further characterized.

  苯丙二酸酯的碱催化转酯化反应可得到苯丙二酸酯。苯丙五酸酯的碱催化转酯化反应可得到苯丙-9,12,13-三乙酸酯。这可以重新乙酰化以得到苯丙-9,12,13,20-四乙酸酯，该化合物也可以通过苯丙-12,13,20-三乙酸酯与乙酸酐/对甲苯磺酸的处理获得。 用LiAlH4还原苯丙-12,13,20-三乙酸酯可得到苯丙-3-醇，该化合物可还原费林试剂和托伦试剂。仅还原3-酮基团可使用硼氢化钠完成。在所有研究的苯丙酯中，仅在苯丙五酸酯中观察到钠硼氢化物还原过程中的乙酰迁移，导致苯丙-3-醇-3,9,12,13,20-五乙酸酯的形成。通过这些发现，苯丙醇中未被乙酸酐/吡啶在室温下乙酰化的两个三级羟基进一步被表征。 用活性二氧化锰氧化苯丙-12,13-二乙酸酯可得到苯丙-20-醛-12,13-二乙酸酯。通过评估该醛及其某些衍生物、苯丙-12,13-二乙酸酯的环氧化物以及6-氧代-7-羟基-和6,7-二乙酰氧基-20-去甲基苯丙-12,13-二乙酸酯的nmr光谱，进一步表征了苯丙烯醇羟基周围的C原子序列。