Carbohydrate-Templated Syntheses of Trifluoromethyl-Substituted MEP Analogues for the Study of the Methylerythritol Phosphate Pathway.

Trifluoromethyl analogues of methylerythritol phosphate (MEP) and 2- C -methyl-erythritol 2,4-cyclodiphosphate (MEcPP), natural substrates of key enzymes from the MEP pathway, were prepared starting from d-glucose as the chiral template to secure absolute configurations. The obligate trifluoromethyl group was inserted with complete diastereoselectivity using the Ruppert-Prakash nucleophile. Target compounds were assayed against the corresponding enzymes showing that trifluoro-MEP did not disrupt IspD activity, whereas trifluoro-MEcPP induced 40% inhibition of IspG at 1 mM.