The sweet natural compound monatin 1 has two stereogenic centres and the (2S,4S) absolute configuration has been attributed to the natural isomer. We obtained all four stereoisomers as pure compounds by a six-step synthetic sequence. The stereogenic centre at C-4 was introduced stereoselectively by a regio-and enantiospecific enzymatic hydrolysis of the racemic ethyl dicarboxylate 4 using a protease from Aspergillus oryzae. The absolute configuration of the intermediate products was assigned by X-ray diffraction of chiral derivatives. The stereogenic centre at C-2 was introduced non-specifically, and the resulting diastereomeric mixtures were separated by RP-HPLC. The absolute configurations of the final products were established by comparing retention

A new class of synthetic compounds with chemesthetic activity has been identified. They have been designed ex‐novo by structural similarity with known cooling compounds such as menthol, icilin and cyclic ketoenamines. 19 new derivatives have been obtained easily and in high yields by Goldberg arylation or lactam ring closure on the appropriate phenol or benzoic acid derivative. The synthetic procedures are suitable for gram‐scale preparation, and the products are stable and easy to purify. 17 new compounds were submitted to preliminary sensory evaluation, and 3 of them showed cooling activity and, in some cases, tingling sensation in the oral cavity. These N‐aryl lactams seem to be an interesting class of compounds to be enlarged in order to derive structure‐activity relationships. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)

The sweet natural compound monatin 1 has two stereogenic centers, and the 2S,4S absolute configuration has been attributed previously to the natural isomer. Among the four stereoisomers of monatin, three of them, particularly the 2R,4R isomer, tastes intensely sweet. The conformations of the four compounds have been studied by means of molecular modelling techniques. Both the diastereoisomeric forms show strong intramolecular hydrogen bonds which involve different functional groups and give rise to two different minimum energy conformations. The tertiary alcohol group in monatin seems to be indirectly involved in the generation of the taste, acting as an important contraint in generating the active conformation. The most important glucophores have

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The interest for sweeteners started well before the systematic study of sweet taste. Nevertheless, it was the hypothesis of the existence of a specific chemoreception mechanism that stimulated organic chemists to consider this area a fertile field for basic research and applications. Organic chemistry has given a large contribute to the elucidation of the sweet taste mechanism and to the discovery of new active compounds. The synthesis of new natural and artificial ligands with an appropriate control of conformational and stereochemical properties; the study of physico-chemical properties in order to optimise chemical stability and solubility; the calculations of molecular descriptors to be used in structure-activity relationships and to develop new models of ligand-receptor interactions: these are only some of the many aspects that an organic chemist could develop in studying sweet taste and sweeteners. The chapter will focus on the experience of our research group in various aspects of organic chemistry applied to the study of sweet taste. 432