One-pot synthesis of poly-substituted tetramic acids for the preparation of putative turn mimics

A one-pot synthesis of poly-substituted tetramic acids and of their six-membered ring analogs have been obtained in one step by reaction of N-Boc dipeptides, activated as their O-succinimidyl esters (Boc-AA-AA-OSu), with the sodium anion of dibenzyl malonate. The adducts spontaneously cyclize to form five or six-member rings. To check whether this class of compounds may be used to promote reverse-turn conformations, one adduct was further derivatized. The formation of a hydrogen bond between the NH-Boc and the carbonyl at C2 of the heterocycle is highlighted, upon analysis of the product by IR, 1H NMR, and MD techniques, thus suggesting that these compounds are good candidates to promote reverse-turn conformations or other secondary structures and may be used for the formation of new foldamers.