Five-Membered Nitrogen Heterocycle Derivatives as Core Structures for the Synthesis of Bioactive Compounds Classes

The research towards new cyclic isosteres of functional groups and the optimization of their synthesis have been one of the basis of this work. In particular, the attention was paid to three different heterocycles: isoxazolines, isoxazolidinones and 3,4-dehydro-beta-prolines. The synthetic protocols developed for them are based on the electrophylic properties of alkylidene acetoacetates, malonates, acetoacetamide esters and malonamides. Their preparation is found on Knöevenagel condensation and a microwaves-assisted protocol.For this last topic, two applications are microwave-assisted protocols for the Yonemitsu-type trimolecular condensation and for the one-pot two-steps synthesis of alkylidene acetoacetamide esters for the preparation of dehydropeptides. The reactivity towards indoles, amines and diprotected hydroxylamines is reported. 1,4-Michael addition of C- and N-nucleophyles to alpha,beta-unsaturated electrophyles is the ground for the synthesis of isoxazolines and isoxazolidinones, differently substituted. Then, the Luche-reduction of these unsaturated intermediates was investigated and the consequent enzymatic resolution for the enantioselective preparation of 3,4-dehydro-beta-prolines. Applications of the synthesized heterocycles in molecules with biological target are the synthesis of Linezolid analogues and peptidomimetic integrin ligands. Finally, the synthesis of red-shifted self-assembled nanoparticles as tools for bioimaging is reported.