Strategies for Combinatorial Organic Synthesis: Solution and Polymer-Supported Synthesis of 4-Thiazolidinones and 4-Metathiazanones Derived from Amino Acids

Article abstract of DOI:10.1021/jo00127a044

Both the solution and polymer-supported synthesis of 4-thiazolidinones and 4-metathiazanones derived from amino acids are described.Solution studies showed that moderate to high yields of 4-thiazolidinones could be obtained from the one-pot, three-component condensation of amino acid esters (glycine, alanine, β-alanine, phenylalanine, and valine) an aldehyde (benzaldehyde, o-tolualdehyde, m-tolualdehyde, m-tolualdehyde, p-tolualdehyde, and 3-pyridinecarboxaldehyde) and an α-mercapto carboxylic acid (thiolacetic acid and mercaptoacetic acid).Acylation of standard peptide synthesis resins with an Fmoc-protected amino acid, followed by deprotection of the Fmoc group and condensation with aldehydes and an α-mercapto or β-mercapto carboxylic acid, lead to the formation of the five- and six-membered heterocycles.The stepwise assembly of 4-thiazolidinones by treatment of the intermediate imine with an α-mercapto carboxylic acid was also demonstrated.Cleavage from the support under acidic (trifluoroacetic acid) conditions gave high yields and high purities of the liberated 4-thiazolidinones and lower yields of 4-metathiazanones.