Synthesis of Two Epimers of Pseudopaline

Abstract

Opines are a known group of compounds characterized by an elevated polarity. Recently, two new members of this class, staphylopine and pseudopaline, have been identified in Staphylococcus aureus and Pseudomonas aeruginosa, respectively. These molecules are metal chelators that contribute to the growth of bacteria in particularly metal‐poor environment. Different evidences suggest that these molecules might have an important role in the development of pulmonary infections in humans. Considering the impact of P. aeruginosa infections in cystic fibrosis patients (prevalence up to 70 %), pseudopaline has risen interest as potential source of new therapeutic intervention. We present herein a straightforward synthetic approach for the synthesis of the two epimers of pseudopaline. Starting from a chiral building block, we attribute the absolute configuration to the two obtained diasteroisomers.

The ancient roots of nicotianamine: diversity, role, regulation and evolution of nicotianamine-like metallophores

“…37 However, in a highly chelating environment, the single mutant lacking cntL revealed such a compromised zinc accumulation, highlighting the importance of this pathway in these conditions. 38 Most of these studies have benefited and will continue to benefit from the input of chemists who not only produce nicotianamine-like molecules 35,54,46,[55][56][57] , but also contribute to their characterization and possible modifications to better understand their mode of action in vivo, as was recently reported for pseudopaline. 56 Recently, the complete export pathway of pseudopaline toward the extracellular space was determined and shown to be mediated by CntI for the crossing of the inner membrane, and also required the efflux pump MexAB, which exports pseudopaline from the periplasm to the extracellular space.…”

Natural products from the human microbiome: an emergent frontier in organic synthesis and drug discovery

“…A variety of siderophores, belonging to hydroximate and/or catechol classes, have been isolated from human Gram −ve pathogens. 56 Notable examples are enterobactin ( 107 , from E. coli and S. typhimurium ), 57 acinetobactin ( 108 , from A. baumannii ), 58 fimsbactin A ( 109 , from A. baumannii ), 59 pseudopalin ( 110 , from P. aeruginosa ), 60 the chromophoric chelator pyoverdin D ( 111 , from P. aeruginosa ), 61 etc ., (Fig. 6) which have been the focus of extensive investigations as antibiotic carriers and diagnostics.…”