Design and parallel solid-phase synthesis of ring-fused 2-pyridinones that target pilus biogenesis in pathogenic bacteria |
| |
Authors: | Emtenäs Hans Ahlin Kristoffer Pinkner Jerome S Hultgren Scott J Almqvist Fredrik |
| |
Affiliation: | Organic Chemistry, Department of Chemistry, Ume? University, SE-901 87 Ume?, Sweden. |
| |
Abstract: | A new method for the solid-phase synthesis of enantiomerically enriched highly substituted ring-fused 2-pyridinones 13 has been developed. The synthesis mediates introduction of substituents at two positions in the 2-pyridinone ring in a diverse manner and is suitable for parallel synthesis. (19)F NMR spectroscopy was used as a tool to monitor each of the five steps in the reaction sequence. The optimized conditions thus obtained were then used to prepare a library of 20 2-pyridinones with high yields. The library members were chosen from a statistical multivariate design to ensure diversity and reliable data for structure-activity relationships. Screening of the library against the bacterial periplasmic chaperone PapD was performed using surface plasmon resonance. Three new 2-pyridinones with a higher affinity for the chaperone PapD than the previous best 13[10,1] were found, and important structural features could be deduced. |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |
|