12-O-,13-O-,20-O-triacetyl(4-deoxy-4α-phorbol) | 33705-05-4

• 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: 12-O-,13-O-,20-O-triacetyl(4-deoxy-4α-phorbol)
• 英文别名: 4-deoxy-4α-phorbol-12,13,20-triacetate；4-Desoxy-4α-phorbol-12,13,20-triacetat；12,13,20-triacetyl-4α-4-deoxyphorbol；4-Desoxyphorbol-12,13,20-triacetate；[(1R,2R,6R,10S,11R,13S,14R,15R)-13,14-diacetyloxy-1-hydroxy-4,12,12,15-tetramethyl-5-oxo-8-tetracyclo[8.5.0.02,6.011,13]pentadeca-3,8-dienyl]methyl acetate
• CAS: 33705-05-4
• 化学式: C₂₆H₃₄O₈
• 分子量: 474.551
• InChiKey: FDCIAGIPBOEVMR-DGSZWRQFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  34
• 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：
  116
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  12-O-,13-O-,20-O-triacetyl(4-deoxy-4α-phorbol) 在 水 、 sodium methylate 作用下， 反应 1.0h， 以80 mg的产率得到4-deoxy-4α-phorbol
  参考文献：
  名称：

  Synthesis and Biological Evaluation of 12-Aminoacylphorboids

  摘要：

  Spurred by the paradoxical anti-inflammatory activity of some aminoacylphorbol derivatives, the naturally occuring and epimeric N,N-dimethylvalinoyl-4 alpha-4-deoxyphorbol derivatives 3b and 3d have been prepared from 4 alpha-4-deoxyphorbol (3e), a byproduct of the isolation of phorbol from Croton oil and a phorboid polyol so far largely overlooked in terms of biological activity. The configuration of the side chain stereocenter was confirmed for both natural products and to investigate the side chain structure-activity relationships within this class of compounds, their corresponding, N,N-dimethylglycinate (3g) and nor (3h) and di-nor derivatives (3i, 3j) were also prepared. By using a PKC-sensitive model of, HIV-1 latency (activation of HIV- gene expression in Jurkat-LAT-GFP cells), it was found that both 3b and 3d can activate PKC-dependent responses, while a series of experiments with isoform-spcefic PKC inhibitors showed that these compounds target PKC alpha and -delta. Both N,N-dimethylation and the presence of side chain alpha-substitution were critical for activity. Selective PKC binding, rather than COX inhibition, might explain the paradoxical anti-inflammatory activity of extracts containing aminoacylphorboids in the mouse ear edema assay.

  DOI：

  10.1021/np9006553
• 作为产物：
  描述：

  4-deoxy-4α-phorbol-12-tigliate 、 alkaline earth salt of/the/ methylsulfuric acid 在 氢氧化钾 作用下， 生成 12-O-,13-O-,20-O-triacetyl(4-deoxy-4α-phorbol)
  参考文献：
  名称：

  Synadenium Grantii的主要皮肤刺激性原则

  摘要：

  Synadenium grantii Hook的乳胶。F。（大戟科）产生了一种新型的皮肤刺激物，即12-O-tigloyl-4-deoxypholia-13-isobutyrate（I）。通过光谱分析和导致I水解和乙酰化的实验，确定了二萜母体醇的身份和酯化基团的相对位置。化合物I是Synadenium属中报道的第一种佛波醇衍生物。

  DOI：

  10.1002/jps.2600691228

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：——
• Synthesis and Biological Evaluation of 12-Aminoacylphorboids
  作者：Alberto Pagani、Carmen Navarrete、Bernd L. Fiebich、Eduardo Muñoz、Giovanni Appendino

  DOI：10.1021/np9006553

  日期：2010.3.26

  Spurred by the paradoxical anti-inflammatory activity of some aminoacylphorbol derivatives, the naturally occuring and epimeric N,N-dimethylvalinoyl-4 alpha-4-deoxyphorbol derivatives 3b and 3d have been prepared from 4 alpha-4-deoxyphorbol (3e), a byproduct of the isolation of phorbol from Croton oil and a phorboid polyol so far largely overlooked in terms of biological activity. The configuration of the side chain stereocenter was confirmed for both natural products and to investigate the side chain structure-activity relationships within this class of compounds, their corresponding, N,N-dimethylglycinate (3g) and nor (3h) and di-nor derivatives (3i, 3j) were also prepared. By using a PKC-sensitive model of, HIV-1 latency (activation of HIV- gene expression in Jurkat-LAT-GFP cells), it was found that both 3b and 3d can activate PKC-dependent responses, while a series of experiments with isoform-spcefic PKC inhibitors showed that these compounds target PKC alpha and -delta. Both N,N-dimethylation and the presence of side chain alpha-substitution were critical for activity. Selective PKC binding, rather than COX inhibition, might explain the paradoxical anti-inflammatory activity of extracts containing aminoacylphorboids in the mouse ear edema assay.
• Major skin-irritant principle from synadenium grantii
  作者：A.Douglas Kinghorn

  DOI：10.1002/jps.2600691228

  日期：1980.12

  Synadenium grantii Hook. f. (Euphorbiaceae) yielded a novel skin irritant, 12-O-tigloyl-4-deoxyphorbol-13-isobutyrate (I). The identity of the diterpene parent alcohol and the relative positions of the esterifying groups were established by spectral analysis and experiments leading to the hydrolysis and acetylation of I. Compound I is the first phorbol derivative to be reported from the genus Synadenium.

  Synadenium grantii Hook的乳胶。F。（大戟科）产生了一种新型的皮肤刺激物，即12-O-tigloyl-4-deoxypholia-13-isobutyrate（I）。通过光谱分析和导致I水解和乙酰化的实验，确定了二萜母体醇的身份和酯化基团的相对位置。化合物I是Synadenium属中报道的第一种佛波醇衍生物。