isophorbol 12,13,20-triacetate | 22338-57-4

• 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: isophorbol 12,13,20-triacetate
• 英文别名: 3-Acetyl-4aα-phorbol-9,9a-diacetat；4α-Phorbol-12,13,20-triacetat；5H-Cyclopropa[3,4]benz[1,2-e]azulen-5-one, 9,9a-bis(acetyloxy)-3-[(acetyloxy)methyl]-1,1a,1b,4,4a,7a,7b,8,9,9a-decahydro-4a,7b-dihydroxy-1,1,6,8-tetramethyl-, (1aR,1bS,4aS,7aS,7bS,8R,9R,9aS)-；[(1S,2S,6S,10S,11R,13S,14R,15R)-13,14-diacetyloxy-1,6-dihydroxy-4,12,12,15-tetramethyl-5-oxo-8-tetracyclo[8.5.0.02,6.011,13]pentadeca-3,8-dienyl]methyl acetate
• CAS: 22338-57-4
• 化学式: C₂₆H₃₄O₉
• 分子量: 490.551
• InChiKey: LASMKIAVFGUYEG-VWKMBUDHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  35
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.69
• 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：

  isophorbol 12,13,20-triacetate 在 silver(l) oxide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 4,13-Di-O-methyl-4α-phorbol-12,20-diacetat
  参考文献：
  名称：

  Jacobi,P. et al., Justus Liebigs Annalen der Chemie, 1970, vol. 741, p. 13 - 32

  摘要：

  DOI：

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。
• Jacobi,P. et al., Justus Liebigs Annalen der Chemie, 1970, vol. 741, p. 13 - 32
  作者：Jacobi,P. et al.

  DOI：——

  日期：——