Synthesis of Dithioacetal-β,β-Digalactosides as Potential Lectin Ligands

Abstract

This work describes the synthesis of novel dithioacetal-digalactoside derivatives as potential inhibitors of Pseudomonas aeruginosa LecA lectin. Pseudomonas aeruginosa is a WHO-classified priority pathogen that uses lectins for biofilm formation, contributing to antibiotic resistance. A library of bivalent and tetravalent thiogalactoside compounds was successfully synthesized through a two-step process involving thioacetalization with aromatic aldehydes followed by Zemplén deacetylation. The synthesized compounds exhibited good to excellent yields and were fully characterized by NMR spectroscopy and mass spectrometry. These sulfur-containing glycomimetics offer enhanced stability compared to natural carbohydrates and represent promising candidates for anti-biofilm therapeutic strategies against antibiotic-resistant bacterial infections.