Diastereoselective synthesis of potent antimalarial cis-β-lactam agents

Document Type: Research article


1 Department of Chemistry, College of Sciences, Shiraz University, Shiraz, 71454, Iran.

2 AixMarseille Université, UMR-MD3 Relation hôte-parasites, Physiopathologie & Pharmacologie, Faculté de pharmacie, Bd Jean Moulin, F-13385, Marseille, France.

3 Aix-Marseille Université,

4 Centre de Recherche en Cancérologie de Marseille (CRCM), CNRS, UMR7258 ; Institut Paoli Calmettes ; AixMarseille Université, UM 105 ; Inserm, U1068, Faculté de pharmacie, Bd Jean Moulin, F-13385, Marseille, France.


Fifteen novel β-lactams bearing the N-ethyl tert-butyl carbamate group 5a-o and fifteen N-(2-aminoethyl) β-lactams 6a-o were synthesized by the ketene-imine [2+2] cycloaddition reaction (Staudinger ). The cycloaddition reaction was found to be totally diastereoselective leading exclusively to the formation of the cis-β-lactam derivatives. These newly synthesized β-lactams were evaluated for their antimalarial activity against p. falciparum K14 resistant strain and showed good to excellent EC50 values. Of the thirty β-lactams tested, 5h, 6a and 6c showed IC50 < 20 µM while 5b, 5c, 5e, 5f, 5g, 5i, 5j, 6d, 6g and 6h exhibited IC50