Total syntheses and antibacterial evaluations of cudraflavones A-C and related Flavones

The total syntheses of the natural prenylated flavones cudraflavones A-C (1-3), artoheterophyllin D (28) and artelasticin (29) are reported, along with the evaluations of their antibacterial activities. The key steps of the synthesis involved a Baker-Venkataraman rearrangement and an intramolecular cyclization for the construction of the flavone core and the regioselective formation of the pyran and isopentenyl scaffolds. The tested natural flavones 1-3 and 27-29 exhibited potent activity against S. aureus ATCC 29213, S. epidermidis ATCC 14990, E. faecalis ATCC 29212 and B. subtilis ATCC 6633 with MIC values ranging from 0.125 & mu;g/mL to 16 & mu;g/mL. Compound 3 displayed the strongest potency, with MIC values in the range between 0.125 and 1 & mu;g/mL, as a potential candidate to combat G+ bacterial infections. Preliminary mechanism of action studies suggested that this compound killed bacteria by disrupting bacterial membrane integrity.