5′,5″-diisoamyltetrahydrocurcumin | 1442415-87-3

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二芳基庚烷
• 英文名称: 5′,5″-diisoamyltetrahydrocurcumin
• 英文别名: 1,7-Bis[4-hydroxy-3-methoxy-5-(3-methylbutyl)phenyl]heptane-3,5-dione；1,7-bis[4-hydroxy-3-methoxy-5-(3-methylbutyl)phenyl]heptane-3,5-dione
• CAS: 1442415-87-3
• 化学式: C₃₁H₄₄O₆
• 分子量: 512.687
• InChiKey: RGQRMXOWQQAADE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.1
• 重原子数：
  37
• 可旋转键数：
  16
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  93.1
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  在 boron trioxide 、 manganese(IV) oxide 、 硼酸三甲酯 、 Lindlar's catalyst 、 palladium 10% on activated carbon 、 氢气 、 正丁胺 作用下， 以 甲醇 、 乙酸乙酯 、 N,N-二甲基苯胺 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 11.0h， 生成 5′,5″-diisoamyltetrahydrocurcumin
  参考文献：
  名称：

  Dissecting the Pharmacophore of Curcumin. Which Structural Element Is Critical for Which Action?

  摘要：

  The dietary phenolic curcumin (1a) is the archetypal network pharmacological agent; but is characterized by an ill-defined pharmacophore. Nevertheless, structure-activity studies of la have mainly focused on a single biological end-point and on a single structural element, the aliphatic his-enoyl moiety. The comparative investigation of more than one end-point of curcumin and the modification of its aromatic region have been largely overlooked. To address these Issues, we have investigated the effect of aromatic C-prenylation in the three archetypal structural types' of curcuminoids namely, curcumin, itself (1a), its truncated analogue 2a (C-5-curcumin), and (as the reduced, isoamyl version) the tetiahydro derivative 3a, comparatively evaluating reactivity with thiols and activity in biochemical (inhibition of NF-kappa B, HIV-1-Tat transactivation, Nrf2 activation) and phenotypic (anti-HIV action) assays sensitive, to a various extent, to thia-Michael addition. Prenylation, a validated maneuver for bioactivity modulation in plant phenolics, had no effect on Michael reactivity but was detrimental for all biological end-points investigated, dissecting thiol trapping from activity, While hydrogenation attenuated, but did not completely abrogate, the activity of 1a. The C-5-curcuminoid 2a outperformed the natural product in all end-points investigated and was identified as a novel high-potency anti-HIV lead in a cellular model of HIV infection. Taken together, these observations show that Michael reactivity is critical element of the curcumin pharmacophore, but also reveal a surprising sensitivity Of bioactivity; to C-prenylation of the vanillyl moiety.

  DOI：

  10.1021/np400148e

文献信息

• Dissecting the Pharmacophore of Curcumin. Which Structural Element Is Critical for Which Action?
  作者：Alberto Minassi、Gonzalo Sánchez-Duffhues、Juan Antonio Collado、Eduardo Muñoz、Giovanni Appendino

  DOI：10.1021/np400148e

  日期：2013.6.28

  The dietary phenolic curcumin (1a) is the archetypal network pharmacological agent; but is characterized by an ill-defined pharmacophore. Nevertheless, structure-activity studies of la have mainly focused on a single biological end-point and on a single structural element, the aliphatic his-enoyl moiety. The comparative investigation of more than one end-point of curcumin and the modification of its aromatic region have been largely overlooked. To address these Issues, we have investigated the effect of aromatic C-prenylation in the three archetypal structural types' of curcuminoids namely, curcumin, itself (1a), its truncated analogue 2a (C-5-curcumin), and (as the reduced, isoamyl version) the tetiahydro derivative 3a, comparatively evaluating reactivity with thiols and activity in biochemical (inhibition of NF-kappa B, HIV-1-Tat transactivation, Nrf2 activation) and phenotypic (anti-HIV action) assays sensitive, to a various extent, to thia-Michael addition. Prenylation, a validated maneuver for bioactivity modulation in plant phenolics, had no effect on Michael reactivity but was detrimental for all biological end-points investigated, dissecting thiol trapping from activity, While hydrogenation attenuated, but did not completely abrogate, the activity of 1a. The C-5-curcuminoid 2a outperformed the natural product in all end-points investigated and was identified as a novel high-potency anti-HIV lead in a cellular model of HIV infection. Taken together, these observations show that Michael reactivity is critical element of the curcumin pharmacophore, but also reveal a surprising sensitivity Of bioactivity; to C-prenylation of the vanillyl moiety.