Synthesis and antimicrobial/antimalarial activities of novel naphthalimido trans-β-lactam derivatives

This paper describes for the first time the synthesis and microbiological assessment of some new beta-lactam derivatives containing a 1,8-naphthalimide functional group. These compounds were obtained through a [2 + 2] cyclocondensation (Staudinger reaction) of a ketene derived from 2-(1,3-dioxo-1H-benzo[de]isoquinolin-2(3H)-yl) acetic acid (Alrestatin) and various N-arylimines. The reaction was totally diastereoselective leading exclusively to the formation of trans-beta-lactam adducts 3a-l, which were characterized by FT-Infra Red, H-1 NMR, C-13 NMR, mass spectrometry, elemental analyses, and X-ray crystallography, and then individually evaluated for antibacterial and antimalarial activities. Two of the beta-lactams, 3c and 3l, afforded IC50 values of 3 and 5 A mu M, respectively, against Plasmodium falciparum K1 resistant strain.