Diastereoselective Synthesis of Potent Antimalarial Cis-β-lactam Agents

Fifteen novel β-lactams bearing n-ethyl tert-butyl carbamate group 5a-o and fifteen n-(2-aminoethyl) β-lactams 6a-o were synthesized by [2+2] ketene-imine cycloaddition reaction (staudinger). the cycloaddition reaction was found to be totally diastereoselective leading exclusively to theformation of 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, 5 h, 6a and 6c showed ic_50 < 20 μm while 5b, 5c, 5e, 5f, 5g, 5i, 5j, 6d, 6g and 6h exhibited ic_50 <50 . compounds 5c, 5h, and 5q-t were examined for their anticancer properties against k562 leukemia cell line and 5s showed the best activity. compounds 3a-j, 5a-o, 6a-o, were tested against s. aureus , e. coli, c. albicans and showed no activity below 125 μg/ml.