Nortriketones: Antimicrobial Trimethylated Acylphloroglucinols from Ma̅nuka (Leptospermum scoparium)

• Published in: Journal of natural products (Washington, D.C.) Vol. 79; no. 3; pp. 564 - 569
• Main Authors: Killeen, Daniel P, Larsen, Lesley, Dayan, Franck E, Gordon, Keith C, Perry, Nigel B, van Klink, John W
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society and American Society of Pharmacognosy 25-03-2016
• Subjects: 4-Hydroxyphenylpyruvate Dioxygenase - drug effects; Anti-Bacterial Agents; Anti-Infective Agents - chemistry; Anti-Infective Agents - isolation & purification; Anti-Infective Agents - pharmacology; Chalcones - chemistry; Chalcones - isolation & purification; Chalcones - pharmacology; Drug Resistance, Bacterial - drug effects; Enterococcus faecalis - drug effects; Escherichia coli - drug effects; Gas Chromatography-Mass Spectrometry; Gram-Positive Bacteria; Herbicides; Ketones - analysis; Leptospermum - chemistry; Methicillin-Resistant Staphylococcus aureus - drug effects; Microbial Sensitivity Tests; Molecular Structure; New Zealand; Nuclear Magnetic Resonance, Biomolecular; Phenylpyruvic Acids; Phloroglucinol - analogs & derivatives; Phloroglucinol - chemistry; Phloroglucinol - isolation & purification; Phloroglucinol - pharmacology; Plant Leaves - chemistry; Vancomycin - pharmacology; New Zealand
• ISSN: 0163-3864; 1520-6025
• DOI: 10.1021/acs.jnatprod.5b00968

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.