Chemical structure and sweet taste of isocoumarins and related compounds

The relationship between sweetness and chemical strucure of 3,4-dihydroisocoumarins was studied because of the interest in the structure of phyllodulcin, the only sweet tasting compound among the naturally occurring 3,4-dihydroisocoumarins. It was found by structural modification of phyllodulcin and the syntheses of various derivatives that β-(3-hydroxy-4-methoxyphenyl) ethylbenzene (XIII) is the essential part of sweet tasting 3,4-dihydroissocoumarins. Further studies on the structural modification of XIII were undertaken to make the relationship between structure and sweet taste clearer. The application of the information obtained from the structure-sweetness relationship of 3,4-dihydroisocoumarins to the design of other series of sweet compounds was attempted. The resulting chroman (LXXXVII), isochroman (LXXXVI), flavanone (LXXXIX), and dihydrochalcone (XCV) derivatives are potently sweet, as was predicted. From these results, it may be concluded that the relationship between sweetness and structure of 5-hydroxyflavanones or dihydrochalcones lacking a glycoside moiety is similar to that of the 3,4-dihydroisocoumarins.