Stereoselective ring contraction of 2,5-diketopiperazines: An innovative approach to the synthesis of promising bioactive 5-membered scaffolds.

Ring contraction of 2,5-diketopiperazines by TRAL-alkylation led us to the stereoselective synthesis of original pyrrolidine-2,4-diones, a novel series of promising molecules with moderate anti-proliferative activity on breast cancer cells.

Regioselective and sequential reactivity of activated 2,5-diketopiperazines.

The electrophilic reactivity of Boc-DKPs has been studied. Thanks to Boc activation, the opening ability of carbonyl lactam groups is enhanced. According to experimental conditions, this enabled the synthesis of Boc-amino acid derivatives or original dipeptides via a regioselective and sequential way.

Transannular rearrangement of activated 2,5-diketopiperazines: a key route to original scaffolds.

An efficient and original stereocontrolled transannular rearrangement starting from activated 2,5-diketopiperazines has been developed, an opportunity for the medicinal chemistry field, which requests access to novel biological scaffolds. This powerful ring contraction, which can be related to a stereoselective aza-version of the Chan rearrangement, allows for example the one-step synthesis of various tetramic acids, access to 2-disubstituted statins, or the synthesis of relevant lactam-constrained dipeptide mimetics using a TRAL-RCM sequence.

Stereocontrolled synthesis of 2,4-diamino-3-hydroxyacids starting from diketopiperazines: a new route for the preparation of statine analogues.

Chiral 3-aminopyrrolidine-2,4-diones, obtained by transannular rearrangement of activated diketopiperazines, could be a springboard toward an exceptional stereoselective synthesis of original 2-disubstituted statines. After a selective reduction of the pyrrolidine-2,4-diones, the access to opened 2,4-diamino-3-hydroxyacid esters was carried out by a subsequent alkaline treatment or directly through a tandem reduction-solvolysis.