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. Fosmidomycin (1a) and FR‐90098 are potent inhibitors of 1‐deoxy‐D‐xylulose‐5‐phosphate reductoisomerase (DXR). The replacement of the hydroxamic acid by functionalized phosphinic acids led to four types of targets which could act as analogues of fosmidomycin.