An intramolecular hydrogen bond-promoted “green” Ugi cascade reaction for the synthesis of 2,5-diketopiperazines with anticancer activity

Abstract

We report an intramolecular hydrogen bond-promoted Ugi cascade reaction for solvent-free synthesis of 2,5-diketopiperazines. Compounds (±) 5c and (±) 5e displayed potent antitumor activity against acute myeloid leukaemia and prostate cancer cell lines, respectively.

Enantioselective Access to Chiral 2,5-Diketopiperazines via Stereogenic-at-Cobalt(III)-Catalyzed Ugi-4CRs/Cyclization Sequences

“…Subsequently, the highly functional Ugi-adducts can be easily transformed into various valuable scaffolds in the following post-Ugi process. Although the Ugi/post-Ugi transformation has been widely used to smoothly construct DKP skeletons, the rareness of extremely challenging enantioselective Ugi four-component reactions (Ugi-4CRs) and the possible racemization in post-Ugi transformations limited the application of Ugi-4CR/post-Ugi sequence in asymmetric catalysis. , The turnaround came in 2018 when Tan, Houk, and co-workers unveiled the first efficient and general enantioselective Ugi-4CRs by using chiral phosphoric acids as catalysts . Recently, our group reported the novel anionic stereogenic-at-cobalt­(III) complex-catalyzed asymmetric Ugi-4CRs and Ugi-azide reactions, delivering α-acylamino amides and α-aminotetrazoles with high-level enantioselectivities .…”