Stereoselective Synthesis of Linear and Cyclic Dehydro-beta-amino Acids for the Preparation of alpha-v-beta-3 and alpha-5-beta-1 Integrin Inhibitors

In a project dealing with the stereoselective synthesis of dehydro-beta-amino acids, we envisaged the insertion of these unusual amino acids as rigid cores in small constrained molecules mimicking the RGD motif, a peptidic sequence recognized by different integrin subtypes as alpha--beta3 and alpha-5-beta-1. Three different libraries of derivatives have been synthesized in few steps starting from alkylidene acetoacetates. The biological evaluation of the prepared inhibitors confirmed that these unusual beta-amino acids may represent interesting scaffolds for the preparation of novel anticancer agents.