One‐Pot Two‐Step Microwave‐Assisted Synthesis of Alkylidene Acetoacetamido Esters, Useful Intermediates for β‐Dehydropeptides

Alkylidene acetoacetamides are useful building blocks for the preparation of a number of biologically active derivatives, including dehydro-β-amino-acid-containing peptidomimetics. A one-pot two-step protocol for the preparation of amino-acid-derived unsaturated acetoacetamides has been optimized. The use of microwave activation avoids, or at least decreases, the need for catalysts in both steps. A leucine derivative was selected from the small collection of molecules obtained to be transformed into the corresponding dehydro-β-amino-acid-containing peptidomimetic. It is known that such fragments are able to induce β-turns into peptide sequences, and, due to the presence of the unsaturation, they may represent sites for selective modification and conjugation.