Sweet Isovanillyl Derivatives: Synthesis and Structure−Taste Relationships of Conformationally Restricted Analogues

In structure-taste relationships of sweet substances, conformational analysis is important for the definition of the "active conformation" which actually interacts with the sweet taste receptor. This paper describes the synthesis and taste of some isovanillyl derivatives having a rigid structure, which can mimick only one possible conformation of their flexible analogues. We report also the solid state conformation of a sulfur-containing sweet isovanillyl derivative which was established by X-ray analysis. The relationships between conformation and taste were studied by comparison with the current models of the sweet taste receptor and by principal components analysis (PCA) using geometrical descriptors, followed by factor and cluster analysis. A strong correlation was proven between taste and geometry, which is able to explain the taste of rigid derivatives as well as the difference of taste between the two enantiomers of the same compound.