Diastereoselective synthesis of potent antimalarial cis-β-lactam agents through a [2 + 2] cycloaddition of chiral imines with a chiral ketene

The effect of double asymmetric induction for the synthesis of new cis-β-lactams by [2 + 2] cycloaddition reactions of chiral imines with a chiral ketene was investigated. The cycloaddition reaction was found to be totally diastereoselective leading exclusively to the formation of the cis-β-lactam derivatives. The newly synthesized cycloadducts were evaluated for their antimalarial activities against Plasmodium falciparum K14 resistant strain with moderate to excellent IC50 values varying from 8 to 50 μM. Of the fifteen β-lactams tested, four showed IC50 ≤ 11 μM. [Display omitted] •The effect of double asymmetric induction for the synthesis of new cis-β-lactams.•[2 + 2] Cycloaddition reactions of chiral imines with a chiral ketene was investigated.•The expected products were in a diastereselective pure form.•Antimalarial activities resistant strain IC50 values varying from 8 to 50 μM.