Synthesis and Evaluation of Sweet Dihydrochalcone Derivatives from Naringin

Naringin was hydrolyzed in hot alkali solution to obtain phloracetophenone-4'-β-neohesperiodoside as an intermediate product for the synthesis of 13 dihydrochalcone glycosides by Claisen Schmidt condensation and O-Michael addition with several benzaldehyde derivatives, where methyl, methoxy, hydroxyl or halogen atoms were introduced into the B ring, followed by catalytic hydrogenation. The structures of these dihydrochalcone glycosides were confirmed by ¹H and ¹³C nuclear magnetic resonance (NMR). The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay was used to investigate their cytotoxic effects on HK2 cells. The survival rate of HK2 cells was more than 80%, indicating no obvious cytotoxicity. Sensory evaluation showed that of the 13 compounds, seven were sweet, five were not sweet and one was bitter. An electronic tongue equipped with sweetness sensors was used to detect the sweetness values of reference substances and the 13 dihydrochalcone glycosides. The results were basically consistent with the sensory evaluation. The correlation analysis between the structures of the dihydrochalcone glycosides and their sweetness showed that the sweetness of dihydrochalcone derivatives with neohesperisyl at position 4 on the A ring was greatly affected by the substituent groups at positions 3' and 4' of the B ring. The seven sweet dihydrochalcone glycosides had no substituent at positions 2' to 6'of the B ring or were connected with OH, F or Cl. Methyl and methoxyl groups were not the key groups contributing to the sweetness.