Preparation of gem-difluorinated retrohydroxamic-fosmidomycin

Jean-Noël Null Volle (1) , Camille Midrier (1) , Vincent Blanchard (1) , Ralph Braun (2) , Klaus Haaf (1) , Lothar Willms (2) , Jean-Luc Pirat (1) , David Virieux (1)

1 ICGM - Institut Charles Gerhardt Montpellier - Institut de Chimie Moléculaire et des Matériaux de Montpellier
2 Bayer CropScience AG

From several decades, some organophosphorus compounds specifically designed to alterbiological systems were introduced on market as agrochemicals (ie glyphosate and glufosinate asherbicides). Nevertheless, it becomes necessary to find new compounds in order to counter plantresistances already observed with glyphosate. Fosmidomicyn and its N-acetyl analogues FR-900098 were perceived as starting points for elaboration of new herbicide candidates, targetingthe second enzyme of the non-mevalonate pathway in plants, the 1-deoxy-D-xylulose 5-phosphate reductoisomerase (DOXP reductoisomerase or DXR). It is expected that theenhancement of bioactivity compared to the parent compounds, might be reached by insertion oftwo fluorine atoms close to the phosphonate function. Indeed, the presence of both fluorineatoms could improve the lipophilicity, affect the pKa of the phosphonic acid function and theninduce better activities. Herein, the synthesis of gem-difluorinated analogues of retrohydroxamicfosmidomycin and FR-900098-ester is reported using a radical addition mediated by acobaloxime complex

Mots clés: DXR; 1-deoxy-D-xylulose 5-phosphate reductoisomerase; hydroxamic acid; DOXP reductoisomerase; Fosmidomycin; phosphonate

Domaines: Chimie organique

Jean-Noël Null Volle, Camille Midrier, Vincent Blanchard, Ralph Braun, Klaus Haaf, et al.. Preparation of gem-difluorinated retrohydroxamic-fosmidomycin. ARKIVOC - Online Journal of Organic Chemistry, 2015, 2015 (4), pp.117-126. ⟨10.3998/ark.5550190.p008.846⟩. ⟨hal-01203792⟩