Shiu, Ka Po Winnie; (2008) Phytochemical and antibacterial studies on the genus Hypericum, with synthesis of antibacterial acylphloroglucinol derivatives. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

This thesis is part of an ongoing project to characterize the antibacterial constituents of the genus Hypericum and to investigate their antibacterial activity. Bioassay-guided fractionation using various chromatography techniques was carried out on six plants in this study. Fifteen natural products were isolated. Their structures were characterized by extensive 1- and 2-dimentional NMR experiments. A panel of Staphylococcus aureus strains was used in minimum inhibitory concentration (MIC) assays to evaluate the antibacterial properties of the plant extracts and isolated compounds. 2,5-dihydroxy-1-methoxyxanthone was isolated from the dichloromethane (DCM) extract of H. forrestii. Fractionation of the DCM extract of H. moserianum and H. revolutum ssp. revolutum yielded 1,7-dihydroxyxanthone and the new 3-hydroxy-1,4,7-trimethoxydibenzofuran respectively. All three compounds were active against various S. aureus strains with MIC values ranging from 128 to 256 μg/ml. Stigmasterol was isolated from the hexane extract of H. beanii. Fractionation of the DCM extract of this plant led to the isolation of 1,7-dihydroxyxanthone and a mixture of two new acylphloroglucinols. (+)-catechin and (-)-shikimic acid were isolated from the methanol extract. The acylphloroglucinol mixture showed MIC values of 16-32 μg/ml. Stigmasterol, (+)-catechin and (-)-shikimic acid were inactive at 512 μg/ml. Fractionation of the hexane extract of H. olympicum L. cf. uniflorum yielded β-sitosterol (inactive at 512 μg/ml) and a new acylphloroglucinol (WS-09; MIC = 0.5 to 1 μg/ml). Fractionation of the DCM extract of this plant yielded four other closely related acylphloroglucinols, with MIC values ranging from 64 to 128 μg/ml. A new pyranone and lupeol were isolated from the hexane and DCM extracts of H. choisianum respectively. Both compounds were inactive at 512 μg/ml. Due to the excellent activity of WS-09, a four-step synthesis method was designed and patented. Twenty-five compounds were synthesized and the structure-activity relationship of various acylphloroglucinol derivatives was investigated.

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