Isovanillyl sweeteners. Synthesis and sweet taste of sulfur heterocycles

As part of an investigation into the structure-sweetness relationship in isovanillyl sweeteners, 15 compounds containing sulfur atoms either in the heterocyclic or the isovanillyl ring have been synthesised and tasted. In general the replacement of oxygen by sulfur maintained or improved the sweetness potency when the heteroatom is in the heterocyclic ring, while the same change in the OH or OMe groups eliminated the sweetness. The most effective structure for generating sweetness is that with a sulfur atom occupying position 1 and an oxygen atom position 3 of a chain, in which the isovanillyl ring is linked to C-2. 2-(3-Hydroxy-4-methoxyphenyl)-4H-3, 1-benzoxathiane 10b(sweet potency 9000) is the sweetest isovanillyl sweetener synthesised until now.