Structure–Activity Relationship Studies of Flavonol Analogues on Pollen Germination

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.