Antimicrobial acylphloroglucinol derivatives from Hypericum linarioides (Hypericaceae)
Hypericum linarioides Bosse (taxonomic section Taeniocarpium) has one center of distribution in western and southern Transcaucasia, adjacent parts of Russia and northern Iran and Turkey, and a second center in southern Serbia, northern Greece and western Bulgaria. Naphthodianthrones, simple anthrones, flavonoids, flavonol glycosides, caffeic acid derivatives and the xanthone-C-glycoside mangiferin have been previously reported from this species [1, 2]. TLC and HPLC screening of an extract of this species collected in western Bulgaria revealed the presence of a rich diversity of acylphloroglucinol derivatives. Correspondingly, bioassay-guided fractionation of the dichloromethane extract of dried, ground aerial parts of H. linarioides was performed, testing extracts against a range of bacterial and fungal pathogens. Upon observation of promising activity against Candida glabrata (IC50=16.91–21.86µg/mL), Cryptococcus neoformans (IC50=2.48–8.43µg/mL), Staphylococcus aureus (IC50=2.98–24.90µg/mL) and MRSA (IC50=2.72–18.99µg/mL), extracts were further fractionated, resulting in the isolation of several structurally related acylphloroglucinol derivatives. Extracts were analyzed by chromatographic means (TLC, OC, HPLC) and structure elucidation performed using data from NMR and MS. This work resulted in the isolation of 3-geranyl-1-(2′-methylbutanoyl)phloroglucinol (1) and 3-geranyl-1-(2′-methylpropanoyl)phloroglucinol (2) as main constituents, as well as several minor derivatives. 1 has been previously reported from H. empetrifolium (sect. Coridium)  and 2 has been previously reported from H. empetrifolium, H. jovis (sect. Coridium)  and H. styphelioides (sect. Brathys) . Implications of this chemical convergence are discussed.
Acknowledgements: This research was supported in part by a grant from the Austrian Science Foundation (FWF, Project T345).
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