Progress in isovanillyl sweet compounds

The so-called isovanillyl sweeteners are organic compounds containing the 3-hydroxy-4-methoxyphenyl moiety, which seems to be essential for the sweet taste of these compounds. Most of them are heterocyclic compounds, with a free rotating isovanillyl group and one chiral carbon atom. Rigid compounds with structures mimicking some of the possible preferred conformations which can be assumed by the isovanillyl sweeteners were prepared and tasted. To establish possible correlations between chirality and taste, the enantioselective synthesis of the (−)-enantiomer of the natural sweet compound (+)-hematoxylin was performed. The sweetest among the isovanillyl compounds was modified by introducing groups apt to interact with the D site of the Nofre-Tinti receptor model. All the results are discussed on the basis of comparison with the most recent models for the sweet taste receptor.