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

摘要

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.