RESUMO
In the anthelmintic cyclooctadepsipeptide PF1022A (1) didepsipeptide units have been exchanged for the beta-turn mimetics (D)-Pro-(L)-Pro and BTD (7) in order to elucidate the functional role of the depsipeptide backbone. Compounds 12 and 14 are the first PF1022A analogues in which a substantial part of the PF1022A backbone has been replaced with an improvement of anthelmintical activity. Preliminary structure-activity relationships suggest a symmetric conformation to be the biological active one.
Assuntos
Anti-Helmínticos/química , Depsipeptídeos/química , Mimetismo Molecular , Anti-Helmínticos/síntese química , Depsipeptídeos/síntese química , Modelos Moleculares , Conformação Molecular , Relação Estrutura-AtividadeRESUMO
Four depsipeptide analogues of the insect neuropeptide proctolin (H-Arg-Tyr-Leu-Pro-Thr-OH) have been prepared, containing a single ester linkage between Arg(1) and Tyr(2), Tyr(2) and Leu(3), and between Pro(4) and Thr(5), respectively. A didepsipentapeptide containing an ester linkage between Tyr(2) and Leu(3) and between Pro(4) and Thr(5), has also been prepared. The depsipeptide 4 is the first example of a backbone-modified proctolin analogue which shows full myotropic activity.