Chalcone-Derived Lactones: Synthesis, Whole-Cell Biotransformation, and Evaluation of Their Antibacterial and Antifungal Activity

Four compounds with lactone moiety were synthesized from chalcone 1 in three- or four-step synthesis. ?-Bromo-d-lactone 5 was the only product of bromolactonization of acid 4 whereas bromolactonization of ester 3, apart from lactone 5 also afforded its isomer 6 and two diastereoisomeric d-hydroxy-?-lactones 7 and 8. Lactone 8 was also obtained in 88% yield as a product of simultaneous dehalogenation and translactonization of ?-bromo-d-lactone 5 by Penicillum frequentans AM 359. Chalcone-derived lactones 5-8 were subjected to the tests on antimicrobial activity and the results compared with activity of starting chalcone 1. Obtained lactones 5-8 in most cases limited the growth of tested bacterial and fungal strains. The highest activity was found for d-hydroxy-?-lactone 8 which completely inhibited the growth of Staphylococcus aureus, Fusarium graminearum, Aspergillus niger, and Alternaria sp. The introduction of lactone moiety into chalcone scaffold significantly improved antimicrobial activity of the compound: ?-bromo-d-lactone 6 and d-hydroxy-?-lactone 8 were significantly stronger growth inhibitors of S. aureus and F. graminearum. In the case of the latter, a clear positive effect of the lactone function on the antifungal activity was also observed for ?-bromo-d-lactone 5.