Synthesis and antibacterial activity of highly oxygenated 1,8-cineole derivatives

Abstract

Seventeen mono-, di- and trifunctionalized 1,8-cineole derivatives carrying OH, OAc, keto and lactone functions at C-5, C-8 and C-9 were synthesized from 1,8-cineole with fair to excellent yields. The antibacterial activity of these synthetic compounds against Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and Staphylococcus aureus using the agar dilution method was examined. Lactones 1,3-dimethyl-2-oxabicyclo[2.2.2]octan-8-endo-acetyloxy- 5→9-olide (15) and 1,3-dimethyl-2-oxabicyclo[2.2.2]octan-8-endo-ol- 5→9-olide (16) showed the highest antibacterial activity against all the three Gram negative bacteria assayed. A structure-activity relationship (SAR) study on the oxygenated 1,8-cineole derivatives has allowed a model to be proposed for the recognition of the minimal structural requirements for the antimicrobial effect.