Synthesis of novel β-lactams and in vitro evaluation against the human malaria parasite Plasmodium falciparum

Abstract

The use of three-component four-center Ugi reactions to afford the synthesis of novel β-lactams is described. Three series of compounds have been made using this reaction in combination with the Mannich reaction. All compounds formed are racemic mixtures and were tested against the chloroquine sensitive D10 strain of Plasmodium falciparum in an in vitro assay. All compounds showed low to moderate microMolar range activity with the most active compounds 2.6 and 3.1 showing IC 50 values 16 µM and 15 µM respectively

Synthesis of Lactams via Isocyanide-Based Multicomponent Reactions

“…The group of Blackie has employed an Ugi-3CR to synthesize -lactams 38 in good to excellent yields (64-84%) by using -alanine (37), cyclohexyl isocyanide and a variety of aromatic aldehydes in MeOH at room temperature. 30 All the Ugi products are racemic mixtures and were screened in an in vitro assay against the chloroquine-sensitive D10 strain of Plasmodium falciparum. All the tested compounds showed low to moderate antimalarial activity (Scheme 6).…”

One step access to oxindole-based β-lactams through Ugi four-center three-component reaction

“…Despite many decades of clinical significance from the discovery of penicillin forward, it remains an interesting pharmacophore for medicinal chemistry and novel applications of β-lactam derivatives continue to be developed. 1 On the other hand, 3-substituted-3-amino-2-oxindoles are also recurring core structures, that can be found in drug molecules and biologically active compounds acting on different targets 2 ( Fig. 1 ).…”