Lost and found in sweeteners: forgotten molecules and unsolved problems in the chemistry of sweet compounds

The chemistry of sweet compounds has been an ideal training ground for researchers in the field of taste for a very long time. Sweeteners have a huge importance in the food and pharmaceutical industries, but they have also attracted much interest in connection with their biological function and the general mechanism of action of sweet compounds. Several factors contributed to a large and varied production of scientific data in this field: among these the existence of several active compounds in the plant kingdom, the diversity of structural, stereochemical and conformational hallmarks, the intriguing aspects related to their modulation, inhibition and synergy. Among all molecules that have been isolated and synthesized, only a few have successfully reached the final goal of commercial development while some have been used to derive models and structure-activity relationships. Nevertheless, there is a number of very interesting compounds of natural or synthetic origin that - after a short period of popularity - were apparently lost or forgotten, without any further development. The article will give an overview on some of these compounds and discuss, in the light of current knowledge, the contribution that chemistry still could give in the sweeteners area.