Fosmidomycin is the first representative of a new class of antimalarial drugs acting through inhibition of1-deoxy-d-xylulose 5-phosphate (DOXP) reductoisomerase (DXR), an essential enzyme in the non-mevalonate pathway for the synthesis of isoprenoids. This work describes a divergent strategy for thesynthesis of a series of α-aryl-substituted fosmidomycin analogues, featuring a palladium-catalyzed Stillecoupling as the key step. An α-(4-cyanophenyl)fosmidomycin analogue emerged as the most potentanalogue in the present series. Its antimalarial activity clearly surpasses that of the reference compoundfosmidomycin.