12-O-[(2R)-N,N-dimethyl-3-methylbutanoyl]-4-deoxyphorbol 13-acetate | 887340-00-3

• 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: 12-O-[(2R)-N,N-dimethyl-3-methylbutanoyl]-4-deoxyphorbol 13-acetate
• 英文别名: N,N-dimethyl-12-(R-valinoyl)-13-acetyl-4α-4-deoxyphorbol；N,N-Dimethyl-12-(R-valinoyl)-13-acetyl-4alpha-4-deoxyphorbol；[(1R,2R,6R,10S,11R,13S,14R,15R)-13-acetyloxy-1-hydroxy-8-(hydroxymethyl)-4,12,12,15-tetramethyl-5-oxo-14-tetracyclo[8.5.0.02,6.011,13]pentadeca-3,8-dienyl] (2R)-2-(dimethylamino)-3-methylbutanoate
• CAS: 887340-00-3
• 化学式: C₂₉H₄₃NO₇
• 分子量: 517.663
• InChiKey: VCEYVQJHAJGATA-MBCQSGEESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  37
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.76
• 拓扑面积：
  113
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  12-O-[(2R)-N,N-dimethyl-3-methylbutanoyl]-4-deoxyphorbol 13-acetate 、 4-溴苯甲酰氯 在 4-二甲氨基吡啶 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 2.5h， 以106.7 mg的产率得到12-O-[(2R)-N,N-dimethyl-3-methylbutanoyl]-20-p-bromobenzoyl-4-deoxyphorbol 13-acetate
  参考文献：
  名称：

  Nitrogen-Containing Phorbol Esters from Croton ciliatoglandulifer and Their Effects on Cyclooxygenases-1 and -2

  摘要：

  Four new phorbol derivatives, 12-O-[(2R)-N,N-dimethyl-3-methylbutanoyl]-4-deoxyphorbol 13-acetate (1), 12-O-[(2S)-N,N-dimethyl-3-methylbutanoyl]-4-deoxyphorbol 13-acetate (2), 12-O-[3-methyl-2-butenoyl]-4-deoxyphorbol 13-acetate (3), and 12-O-[(2R)-N, N-dimethyl-3-methylbutanoyl] phorbol 13-acetate ( 4), along with six known compounds, were isolated from the aerial parts of Croton ciliatoglandulifer. An anti-inflammatory activity of a hexane extract of this plant was demonstrated against ear edema in mice produced by 12-O- tetradecanoylphorbol 13-acetate, and compounds 1, 4, and 3 beta-O-acetyloleanolic acid (5) were active when evaluated against cyclooxygenases-1 and -2.

  DOI：

  10.1021/np0504311
• 作为产物：
  描述：

  聚合甲醛 、 12-(R-valinoyl)-13-acetyl-4α-4-deoxyphorbol 在 三乙酰氧基硼氢化钠 、 溶剂黄146 作用下， 以 水 、 乙腈 为溶剂， 反应 1.08h， 以80%的产率得到12-O-[(2R)-N,N-dimethyl-3-methylbutanoyl]-4-deoxyphorbol 13-acetate
  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

文献信息

• 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.
• Nitrogen-Containing Phorbol Esters from <i>Croton </i><i>c</i><i>iliatoglandulifer</i> and Their Effects on Cyclooxygenases-1 and -2
  作者：María Yolanda Rios、A. Berenice Aguilar-Guadarrama

  DOI：10.1021/np0504311

  日期：2006.6.1

  Four new phorbol derivatives, 12-O-[(2R)-N,N-dimethyl-3-methylbutanoyl]-4-deoxyphorbol 13-acetate (1), 12-O-[(2S)-N,N-dimethyl-3-methylbutanoyl]-4-deoxyphorbol 13-acetate (2), 12-O-[3-methyl-2-butenoyl]-4-deoxyphorbol 13-acetate (3), and 12-O-[(2R)-N, N-dimethyl-3-methylbutanoyl] phorbol 13-acetate ( 4), along with six known compounds, were isolated from the aerial parts of Croton ciliatoglandulifer. An anti-inflammatory activity of a hexane extract of this plant was demonstrated against ear edema in mice produced by 12-O- tetradecanoylphorbol 13-acetate, and compounds 1, 4, and 3 beta-O-acetyloleanolic acid (5) were active when evaluated against cyclooxygenases-1 and -2.