Chemical Investigations of Australian Marine Sponges

Abstract

This thesis describes the isolation and structure elucidation of a series of natural products from six different marine sponges collected from Australian waters. A total of nineteen sponge metabolites were isolated, four of which had not been reported previously. The structures of these compounds were elucidated by spectroscopic methods. An investigation into two sponges from the Adocia genus revealed a series of novel compounds related to the proton pump inhibitor adociasulfate 1 (3.22). Adociasulfates 7 (3.24) and 8 (3.25), along with adociasulfate 1 were isolated from an Adocia aculeata collected from Lizard Island. Another sample of Adocia aculeata collected from Cormorant Pass, North Great Barrier Reef, yielded adociasulfates 5 (3.23) and 9 (3.26). In the course of the study it was found that the adociasulfates were present only in the extracts of Adocia aculeata samples and not other Adocia species, thus revealing a possible chemotaxonomical relationship. The investigation of three sponges, whose extracts showed inhibition of [3H]DPCPX binding to rat-brain adenosine A1 receptors, yielded ten compounds, one of which was novel. An investigation into a Pseudoceratina sp. collected from Swain Reefs, Queensland resulted in the isolation of the new bromotyrosine derived ianthesine E (4.24) and the known related compounds aerothionin (4.20), 11-hydroxyaerothionin (4.21), 19-deoxyfistularin 3 (4.22), and 11,19-dideoxyfistularin 3 (4.23). Aerothionin was found to be the most active of this series of compounds, inhibiting 67% binding of [3H]DPCPX at 100 ìM. Interpretation of HMBC NMR spectra of these compounds and comparison with data reported previously for related bromotyrosine compounds revealed that some data in the literature had been misassigned. Investigations into a Xestospongia pacifica and a Phakellia flabellata collected from Swain Reefs resulted in the isolation of a series of five known metabolites. Debromohymenialdsine (4.71) was isolated from Phakellia flabellata and was found to be the most effective inhibitor of [3H]DPCPX binding (79% at 100ìM) to the adenosine A1 receptor of all of the compounds tested as part of this research. Also isolated from this sponge were aldisine (4.69) and norzooanemonin (4.70). 1,3-dimethylguanine (4.48) was isolated from Xestospongia pacifica, and this compound showed 61% inhibition of [3H]DPCPX binding to the adenosine A1 receptor at 100ìM. N-methyltaurine (4.55) was also isolated from this sponge in a crystalline form. The XRD analysis of the crystal revealed extensive hydrogen bonding interactions between the amine H atoms and sulfonyl O atoms in the zwitterionic molecule. Chemical investigation of a Mycale sp. collected from Stephen's Rock, Darwin, Northern Territory resulted in the isolation of the nucleosides uridine (5.13), 2'- deoxyuridine (5.14), 2'-deoxyinosine (5.16) and the pyrimidine base thymine (5.15). Uridine and 2-deoxyinosine were tested for inhibition of [3H]DPCPX binding to adenosine A1 receptors. Uridine inhibited 45% of binding at 100ìM while 2- deoxyinosine inhibited 34% binding at the same concentration. Cytotoxicity screening of the sponge metabolites against the HeLa cell line revealed that 11,19-dideoxyfistularin-3 with an EC50 of 2.6 ìM was the most potent cytotoxin of all of the compounds isolated. Aerothionin was the next potent with an EC50 of 42 ìM while adociasulfate 8 was found to be the most cytotoxic of the four adociasulfates screened with an EC50 of 68 ìM.