Nortriketones: Antimicrobial Trimethylated Acylphloroglucinols from Ma̅nuka (Leptospermum scoparium)

Four trimethylated acylphloroglucinols (5-8) have been isolated from ma̅nuka (Leptospermum scoparium) foliage. Apart from myrigalone A (8), which has previously been isolated from European bog myrtle (Myrica gale), these compounds have not been characterized before. The nortriketones are structurally similar to the bioactive tetramethylated β-triketones from ma̅nuka, but have one less ring methyl group. Two oxidized trimethylated compounds, 9 and 10, were also isolated, but these are likely isolation artifacts. When evaluated for antibacterial activity against Gram-positive bacteria, myrigalone A (8) was slightly less potent (MIC 64 μg/mL) than the corresponding tetramethylated compound, grandiflorone (4) (MIC 16-32 μg/mL). Unlike their tetramethylated analogues, the nortriketones were inactive against the herbicide target enzyme p-hydroxyphenylpyruvate dioxygenase. The Raman spectra of leaf oil glands in different ma̅nuka varieties can be used to distinguish plants that contain nortriketones from those that accumulate triketones.