Synthesis of some new monocyclic β-lactams as antimalarial agents

A series of new monocyclic β-lactams bearing several methoxy groups and possessing a similar meticillin structure was prepared by the ketene–imine [2+2] cycloaddition reaction (Staudinger reaction). The cycloaddition reaction was found to be totally diastereoselective for 3a-l (electron donating phenoxy ketenes) and 3u leading exclusively to the formation of cis-β-lactams while 3m-o, 3q-s, and 3v-x were formed as trans diastereomer. β-lactams 3p, 3t, and 3y were found to be a mixture of cis/trans diastereomers. Compounds 3a-x were tested against chloroquine-resistant p. falciparum K14 strain and showed low to excellent activities with IC50 varying from 5 to 50 µM.