Department of Chemistry, Fulmer 305, Washington State University , Pullman, Washington 99164-4630, United States.
J Agric Food Chem. 2014 Mar 12;62(10):2175-81. doi: 10.1021/jf405688d. Epub 2014 Feb 27.
Flavonoids are polyphenolic compounds required in the fertilization process in many, if not all, plants. However, the exact biological mechanism(s) and the interacting proteins are unknown. To determine the characteristics important in activating or inhibiting the pollination sequence, a structure-activity relationship analysis of natural and synthetic flavonols was conducted. Flavonol analogues were synthesized through a modified "one-pot" procedure that utilized a Baker-Venkataraman type rearrangement and a Suzuki-Miyaura cross-coupling of a halo-flavonol with an organotrifluoroborate. Of the flavonols tested, kaempferol was the only compound to act as a full agonist. The other smaller, less sterically hindered flavonols (galangin, kaempferide, and 4'-methyl flavonol) acted as partial agonists. Larger more hydrophobic flavonol analogues (3'- and 4'-benzoyl, 3'- and 4'-phenyl, and 3'- and 4'-iodo flavonols) had minimal or no agonist activity. Competition assays between kaempferol and these minimally activating flavonols showed that these analogues inhibited the action of kaempferol in a manner consistent with noncompetitive antagonism. The results suggest that steric hindrance is the most important factor in determining a good agonist. Hydrogen bonding also had a positive effect as long as the substituent did not cause any steric hindrance.
类黄酮是许多（如果不是全部）植物受精过程中所需的多酚化合物。然而，确切的生物学机制和相互作用的蛋白质尚不清楚。为了确定在激活或抑制授粉序列中重要的特征，对天然和合成类黄酮醇进行了结构-活性关系分析。通过改良的“一锅煮”程序合成了类黄酮醇类似物，该程序利用了Baker-Venkataraman 型重排和卤代类黄酮醇与有机三氟硼酸盐的Suzuki-Miyaura 交叉偶联。在所测试的类黄酮醇中，山奈酚是唯一具有完全激动剂作用的化合物。其他较小、位阻较小的类黄酮醇（根皮素、山奈酚苷和 4'-甲基类黄酮醇）作为部分激动剂。较大、疏水性更强的类黄酮醇类似物（3'-和 4'-苯甲酰基、3'-和 4'-苯基和 3'-和 4'-碘代类黄酮醇）几乎没有或没有激动剂活性。山奈酚与这些最小激活类黄酮醇之间的竞争测定表明，这些类似物以非竞争性拮抗的方式抑制山奈酚的作用。结果表明，位阻是决定良好激动剂的最重要因素。只要取代基不引起任何位阻，氢键也有积极的影响。
