title: Multicomponent synthesis and anticonvulsant activity of monocyclic 2,6-diketopiperazine derivatives.
abstract: In this study, a series of diastereomerically pure monocyclic 2,6-diketopiperazine (2,6-DKP) derivatives were synthesized. The key synthetic step involved a multicomponent Ugi five-center, four-component reaction which was used to generate the convertibletert-butylamidoesters with both good yields and high diastereoselectivity toward the desired bioactive (S,S) absolute configuration. In subsequent steps, selectivetertbutyl cleavage by use of BF3·CH3COOH and base-induced intramolecular cyclocondensation gave the final 2,6-DKP derivatives. The relative stereochemistry of the target molecules was confirmed by1H NMR experiments. The compounds obtained were submitted to in vivo screening in animal models of epilepsy. Some of them displayed good activity in maximal electroshock seizure and 6 Hz tests.
authors.affiliation: Department of Drug Technology and Pharmaceutical Biotechnology, Medical University of Warsaw, Banacha 1 Str., 02-097 Warsaw, Poland.
authors.forename: Maciej
authors.initials: M
authors.lastname: Dawidowski
authors.affiliation: Department of Drug Technology and Pharmaceutical Biotechnology, Medical University of Warsaw, Banacha 1 Str., 02-097 Warsaw, Poland.
authors.forename: Jadwiga
authors.initials: J
authors.lastname: Turło
keywords: 2,6-Diketopiperazine; 2,6-Piperazinedione; Anticonvulsant activity; Multicomponent reactions; Ugi reaction