A sustainable approach to 1,3-Oxathiolan-5-ones and their identification as a new anthelmintic scaffold

We report an efficient and sustainable solvent-free microwave protocol for the synthesis of a diverse library of 1,3-oxathiolan-5-ones from aromatic, aliphatic, and sugar-derived aldehydes. The method requires no catalysts or organic solvents and furnishes fifteen derivatives in good to excellent isolated yields (62-98%) within 40 min, demonstrating broad functional-group tolerance, excellent atom economy, and operational simplicity. While 1,3-oxathiolanes are known to exhibit biological activity such as antiviral effects, the corresponding 1,3-oxathiolan-5-ones remain comparatively underexplored. To investigate the biological responsiveness of this scarcely explored heterocyclic scaffold, the compounds were evaluated for anthelmintic effects using Caenorhabditis elegans as a validated whole-organism model. Several derivatives induced measurable impairments in motility and survival at sub-millimolar concentrations, revealing a substituent-dependent trend in activity. These findings are consistent with an early-stage phenotypic screening approach aimed at identifying biologically responsive scaffolds rather than optimized anthelmintic agents. To the best of our knowledge, these results represent the first report describing anthelmintic effects associated with 1,3-oxathiolan-5-ones in a whole-organism model. Complementary in silico Absorption, Distribution, Metabolism, and Excretion (ADME) predictions showed that the most active derivatives fall within physicochemical and pharmacokinetic space associated with oral drug-likeness, further supporting their suitability for follow-up studies. Overall, this work establishes a synthetically accessible and previously underexplored heterocyclic framework that combines green synthetic access, structural diversity, and preliminary biological activity in a whole-organism context. The findings highlight 1,3-oxathiolan-5-ones as potential starting points for further optimization in anthelmintic research and as useful scaffolds for broader applications in medicinal and heterocyclic chemistry.