A mechanochemical approach to access the proline-proline diketopiperazine framework.
Ball milling was exploited to prepare a substituted proline building block by mechanochemical nucleophilic substitution. Subsequently, the mechanocoupling of hindered proline amino acid derivatives was developed to provide proline-proline dipeptides under solvent-free conditions. A deprotection-cyclization sequence yielded the corresponding diketopiperazines that were obtained with a high stereoselectivity which could be explained by DFT calculations. Using this method, an enantiopure disubstituted Pro-Pro diketopiperazine was synthesized in 4 steps, making 5 new bonds using a ball mill.
['Pétry|Nicolas|N|', 'Benakki|Hafid|H|', 'Clot|Eric|E|', 'Retailleau|Pascal|P|', 'Guenoun|Farhate|F|', 'Asserar|Fatima|F|', 'Sekkat|Chakib|C|', 'Métro|Thomas-Xavier|TX|', 'Martinez|Jean|J|', 'Lamaty|Frédéric|F|']
diketopiperazine ball mill DFT calculations mechanochemistry pyrrolidine