Synthetic and biosynthetic studies of the phosphonate antibiotic A53868

ORGN 664

John Thomas Whitteck, jwhitte2@uiuc.edu and Wilfred A. van der Donk, vddonk@uiuc.edu. Department of Chemistry, University of Illinois at Urbana-Champaign, 600 S. Mathews, 161 RAL, Box 38-5, MC 712, Urbana, IL 61801
Phosphonate antibiotics are used commercially as pharmaceuticals, herbicides, and pesticides. This wide range of biological activity is due to the fact that phosphonates can serve as substrate mimics of phosphorylated or carboxylated intermediates in biochemical pathways. However, relatively little work has been done to elucidate the biosynthesis of this class of compounds. One particular phosphonate, A53868, which is produced by Streptomyces luridus, is of interest due to a broad spectrum of activity against both Gram-negative and Gram-positive bacteria. Herein we report the total synthesis of A53868 and the results of our investigation into the biosynthetic pathway.