STRUCTURE-TASTE CORRELATIONS IN SWEET DIHYDROCHALCONE, SWEET DIHYDROISOCOUMARIN, AND BITTER FLAVONE COMPOUNDS

The dihydrochalcone derivatives of the bitter flavonoids naringin and neohesperedin are intensely sweet. Phyllodulcin is as sweet as the dih ydrochalcones with similar taste properties although its structure app arently resembles that of bitter flavanone or flavone. Multifaceted ap proaches, including X-ray crystal structure analysis, energy calculati on, and structure comparison, have been employed to clarify the struct ure-taste correlations in these classes of compounds. In the crystal, naringin dihydrochalcone assumes a 'J'-shaped conformation with a full y-extended dihydrochalcone moiety while neohesperidin dihydrochalcone assumes the same overall conformation but with a partially-extended mo iety. A 2D conformational energy map of dihydrochalcone obtained using molecular mechanics revealed nine local minima. The pseudoequatorial and pseudoaxial forms of phyllodulcin have the same AM1 energies with a low energy barrier between them. The partially-extended form of dihy drochalcone and the pseudoequatorial form of phyllodulcin which are th e maximally superposable conformers are proposed to be the active conf ormers. The major difference between the structures of flavone and phy llodulcin is not in the overall planarity but in the relative orientat ion of the pyrone and phenyl ring systems.