Establishing the Intermediates in the Biosynthesis of the Phosphonate Antibiotic A53868
The impact of new infections that are antibiotic resistant is a critical issue which could potentially be combated with the novel phosphonate antibiotic A53868. In this research, the synthesis of 1,2-dihydroxyethyl phosphonic acid and (1-amino-2-hydroxyethyl)phosphonic acid, two putative intermediates in the biosynthesis of A53868, was attempted. These two compounds are necessary for the elucidation of the biosynthetic pathway of A53868. Osmium-catalyzed asymmetric dihydroxylation and quantitative dealkylation of alkyl esters via treatment with trimethylsilyl iodide were used in the synthesis of 1,2-dihydroxyethylphosphonic acid. In addition, (1-amino-2-hydroxyethyl)phosphonic acid was produced from benzyl carbamate, (benzyloxy)acetaldehyde and trimethyl phosphite in a one-pot reaction. The products of these two syntheses were purified by column chromatography, and 31P NMR and 1H NMR spectroscopy were used as effective tools to confirm the identity of these two intermediates.
School:
University of Puerto Rico at Río Piedras
Department:
Chemistry
Research Advisor:
Wilfred van der Donk
Department of Research Advisor:
Chemistry
Year of Publication:
2007