Preparation of gem-difluorinated retrohydroxamic-fosmidomycin

From several decades, some organophosphorus compounds specifically designed to alter biological systems were introduced on market as agr ochemicals (ie glyphosate and glufosinate as herbicides). Nevertheless, it becomes necessary to find new compounds in order to counter plant resistances already observed with glyphosate. Fosmi domicyn and its N-acetyl analogues FR900098 were perceived as starting points for elabor ation of new herbicide candidates, targeting the second enzyme of the non-mevalonate pathway in plants, the 1-deoxy-D-xylulose 5phosphate reductoisomerase (DOXP reductoisomerase or DXR). It is expected that the enhancement of bioactivity compared to the parent c ompounds, might be reached by insertion of two fluorine atoms close to the phosphonate functio n. Indeed, the presence of both fluorine atoms could improve the lipophilicity, affect the p Ka of the phosphonic acid function and then induce better activities. Herein, the synthesis of gem-difluorinated analogues of retrohydroxamic fosmidomycin and FR-900098-ester is reported using a radical addition mediated by a cobaloxime complex.