Marine and terrestrial natural products discovery

This thesis describes the natural product study of three Australian plants and two southern Australian marine algae. The application of the hyphenated spectroscopic technique, HPLC-NMR, was successfully implemented in the partial identification or as a dereplication of the secondary metabolites present in each of the studied organisms. HPLC-NMR was particularly suited to the identification of an unstable new secondary metabolite identified from one of the marine organisms. In total this thesis resulted in the isolation and structural elucidation of five new secondary metabolites, one new X-ray crystal structure of a previously reported compound and twenty-two known secondary metabolites, of which five structural and/or chemical shift re-assignments were deduced. On-line (HPLC-NMR) and off-line (HPLC, NMR and MS) profiling of the Australian plant Lasiopetalum macrophyllum allowed for the identification of four flavonoid glycosides, including a new structural analogue. This study represented the first report of flavonoid glycosides occurring within this plant genus. The study of the Australian plant Haemodorum simulans was carried out using a combination of on-line (HPLC-NMR) and off-line (HPLC, NMR, MS) methodologies. This resulted in the isolation of two new phenylphenalenones from the bulbs of the plant, along with the first report of an oxabenzochrysenone glycoside, which was isolated from the aerial parts of the plant. Four previously reported secondary metabolites including two phenylphenalenones and two oxabenzochrysenones were also isolated, with the first X-ray structure of one of the phenylphenalenones also obtained. The HPLC-NMR chemical profiling study of the crude extract derived from the bulbs of the Australian carnivorous plant Drosera erythrohiza subspecies magna resulted in the partial identification of two naphthoquinones, as well as a mixture of two naphthoquinone glycosides.

Subsequent off-line isolation (semi-preparative HPLC) of these secondary metabolites, followed by NMR spectroscopic and mass spectrometric analyses of the crude extract from the bulbs resulted in the identification of two naphthoquinones and two naphthoquinone glycosides. In addition to this off-line methodologies were utilised to isolate a further naphthoquinone from the aerial parts of this plant. Biological activity studies concluded that one of the naphthoquinones possessed potent broad spectrum activity. The study of the Australian marine red alga Plocamium angustum led to the identification of one new and one previously reported secondary metabolites. This led to the structural re-assignment of the previously reported secondary metabolite plocamenone. This compound displayed potent broad spectrum biological activity. An on-line chemical profiling/dereplication study of the Australian brown alga Cystophora torulosa, using HPLC-NMR in combination with the use of the MarinLit database led to the identification of two classes of secondary metabolites, resorcinol derivatives and polyenes. In total seven secondary metabolites were identified by on-flow HPLC-NMR analysis, including five resorcinol derivatives and two polyenes. Off-line small-scale analytical HPLC collection and subsequent ESI-MS or GC-MS analyses of the crude extract allowed for the identification of a total of nine secondary metabolites including seven resorcinol derivatives and two polyenes with the aid of the MarinLit database.