α,α-Difluorophosphonohydroxamic Acid Derivatives among the Best Antibacterial Fosmidomycin Analogues

Abstract

Three α,α-difluorophosphonate derivatives of fosmidomycin were synthesized from diethyl 1,1-difluorobut-3-enylphosphonate and were evaluated on Escherichia coli. Two of them are among the best 1-deoxy-d-xylulose 5-phosphate reductoisomerase inhibitors, with IC50 in the nM range, much better than fosmidomycin, the reference compound. They also showed an enhanced antimicrobial activity against E. coli on Petri dishes in comparison with the corresponding phosphates and the non-fluorinated phosphonate.

Keywords

• α,α-difluorophosphonate
• deoxyxylulose phosphate reductoisomerase
• dxylulose 5-phosphate reductoisomerase (DXR)%22%2C%22default_operator%22%3A%22AND%22%7D%7D%7D"> 1-deoxy-<span style="font-variant: small-caps">d</span>xylulose 5-phosphate reductoisomerase (DXR)
• antimicrobial
• fosmidomycin
• isoprenoid biosynthesis