Isoprenoid biosynthesis via the methylerythritol phosphate pathway: structural variations around phosphonate anchor and spacer of fosmidomycin, a potent inhibitor of deoxyxylulose phosphate reductoisomerase

The synthesis of analogues of the two reverse phosphonohydroxamic acids is described, in which the length of the carbon spacer is modified, the N-methyl group of the acid is replaced by an ethyl group and the phosphate group is replaced by isosteric moieties like sulfonate or carboxylate functionalities. The potential of the analogues to inhibit the Escherichia coli 1-deoxy-D-xylulose 5-phosphate reducto-isomerase (DXR) is analyzed.