Functionalized Phosphanyl-Phosphonic Acids as Unusual Complexing Units as Analogues of Fosmidomycin

Fosmidomycin (1a) and FR-90098 are potent inhibitors of 1-deoxy-D-xylulose-5-phosphate reductoisomerase (DXR), the second enzyme of the non-mevalonate (MEP) pathway responsible for the biosynthesis of isoprenoids. This paper describes the synthesis of four types of targets bearing a phosphanyl-phosphonic acid motif as the common core for the inhibition of DXR. In these structures, the hydroxamic acid was replaced by various chelators based on a phosphinic acid linked to different functional groups capable of forming five- or six-membered chelating rings.