One-Pot Phosphate-Mediated Synthesis of Novel 1,3,5-Trisubstituted Pyridinium Salts: A New Family of S. aureus Inhibitors

• Published in: Molecules (Basel, Switzerland) Vol. 22; no. 4; p. 626
• Main Authors: Pesnot, Thomas, Gershater, Markus C, Edwards, Martin, Ward, John M, Hailes, Helen C
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 12-04-2017; MDPI
• Subjects: Acids; Aldehydes; Amines; Anti-Bacterial Agents - chemical synthesis; Anti-Bacterial Agents - pharmacology; Biological activity; Chemistry Techniques, Synthetic; Condensation; Disk Diffusion Antimicrobial Tests; Molecular Structure; Pharmacology; Pharmacophores; Phosphates; Phosphates - chemistry; Pyridines; Pyridinium Compounds - chemical synthesis; Salts; Salts - chemical synthesis; Staphylococcus aureus - drug effects; Sustainability; antibacterial activity; pyridinium salts; synthesis in water; heteroaromatic synthesis; Chichibabin reaction
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules22040626

Polysubstituted pyridinium salts are valuable pharmacophores found in many biologically active molecules. Their synthesis typically involves the use of multistep procedures or harsh reaction conditions. Here, we report water-based phosphate mediated reaction conditions that promote the condensation of arylacetaldehydes with amines to give 1,3,5-pyridinium salts. The reaction, carried out at pH 6, provides conditions suitable for the use of less stable aldehydes and amines in this Chichibabin pyridine condensation. The evaluation of selected 1,3,5-trisubstituted pyridinium salts highlighted that they can inhibit the growth of
in the low μg/mL range. The synthetic accessibility of these compounds and preliminary growth inhibition data may pave the way towards the discovery of new anti-bacterials based on the 1,3,5-trisubstituted pyridinium scaffold.