Marine Natural Products from South-East Queensland: Secondary Metabolites from Sponges and Nudibranchs

Michael Somerville (2010). Marine Natural Products from South-East Queensland: Secondary Metabolites from Sponges and Nudibranchs PhD Thesis, School of Chemistry and Molecular Biosciences, The University of Queensland.

       
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Author Michael Somerville
Thesis Title Marine Natural Products from South-East Queensland: Secondary Metabolites from Sponges and Nudibranchs
School, Centre or Institute School of Chemistry and Molecular Biosciences
Institution The University of Queensland
Publication date 2010-08
Thesis type PhD Thesis
Supervisor Mary Garson
Joanne Blanchfield
Total pages 183
Total colour pages 9
Total black and white pages 174
Subjects 06 Biological Sciences
Abstract/Summary Historically, the marine environment, in particular reef systems and the organisms which inhabit them, has been a bountiful source of new molecular types and skeletons. The main goal of this PhD research was to investigate the secondary metabolite composition of sponges and nudibranchs from the reefs of the Sunshine Coast, Queensland, Australia. Where possible, evaluation of potential bioactivity of these metabolites was to be performed. Structure elucidation of all isolated compounds was carried out using assorted spectral methods including various 1D and 2D nuclear magnetic resonance (NMR) techniques and mass spectrometry (MS). In total, 4 mollusc and 2 sponge species from Sunshine Coast reefs were investigated. Secondly, in the pursuit of finding new bioactive molecules and investigating their structure activity relationships, a small library of synthetic analogues of stylotellane A (5.1.2) was synthesised and assayed for anticancer potential. From the nudibranch Glossodoris atromarginata seven compounds of the spongian furanoditerpene series were isolated. The nudibranch was dissected prior to analysis into three different body compartments and each was analysed individually. Two new natural products spongia-13,(16),14-dien-3-one (2.2.1) 3α-acetoxy-19-hydroxyspongia-13,16(14)-dien-2-one (2.2.2) together with the known compounds (2.2.3 - 2.2.7) were obtained. Interestingly, the discovery of compounds belonging to different C-3 epimeric series in either the mantle or digestive tissue indicates that the nudibranch may be selectively compartmentalising these compounds. The possibility that the isolated compounds are of dietary origin led to the analysis of a small sponge sample of unknown taxonomy and preliminary data is presented. Furthermore, these results constitute the third study of G. atromarginata and are the second to discover diterpenes providing further geographical and chemotaxonomic data for this species. As part of the search to find the dietary sponge of G. atromarginata, the grey sponge Hyattella intestinalis was analysed. Purification of the secondary metabolites from this sponge resulted in the isolation of six new natural products comprising five C24 norscalarane compounds, mooloolabenes A-E (3.2.1 - 3.2.5) and one regular (C25) scalarane (3.2.6). The mooloolabenes A-E represent a new pattern of norscalarane functionality with the presence of a Δ7 double bond. Evaluation of 3.2.1 - 3.2.6 proved them to show no useful antimicrobial activity yet all were shown to inhibit the growth of mouse leukemia P388 cells with mooloolabenes A and B the most potent (IC50 0.8 and 1.2 μg/mL respectively). Motivated by the prolific species diversity of nudibranchs located at the Sunshine Coast reefs and by results obtained from the investigation of G. atromarginata, investigation of the secondary metabolite composition of three mollusc species was performed. From the nudibranch Bornella anguilla one known compound, prostaglandin F2α-1,15-lactone-11-acetate (4.2.1) was obtained and full structure assignment was achieved. The white nudibranch Tritoniopsis elegans was also investigated resulting in the isolation of two known cladiellane compounds cladiella-11(17),6-dien-3-ol (4.3.15) and cladiella-6,11-dien-3-ol (4.3.16) and one new compound, tentatively named 11-acetoxycladiella-6,7-diol (4.3.14). Collection and subsequent investigation of the sacoglossan mollusc Thuridilla splendens resulted in the isolation of three new diterpene natural products thuridillins D-F (4.4.5 - 4.4.7) and one known compound, thuridillin A (4.4.1). This is only the second time that thuridillins have been isolated: they were originally obtained from Thuridilla hopei a sacoglossan belonging to the same genus. This research represents the first chemical investigation for all three species of mollusc while being a first for the genera Bornella and Tritoniopsis. To probe the structure activity relationships of compounds analogous to stylotellane A (5.1.2) and evaluate their anticancer potential, eight compounds were synthesised (5.2.1 - 5.2.8). Synthesis was performed so that the final compounds contained an all trans farnesyl (C15) backbone with variation arising from the alteration of N-linked functional groups. The synthesis of these eight compounds had not previously been described in the scientific literature. The synthetic analogues were tested for their potential growth inhibitory and cytotoxic ability against three human cancer cell lines comprising breast (H460), lung (MCF-7) and central nervous system glioblastoma (SF268) cancer. Overall, the most active compounds were found to be urea functionalised analogues 5.2.5 and 5.2.6.
Keyword sponge
nudibranch
sunshine coast
hyattella
glossodoris
bornella
tritoniopsis
thuridilla
farnesylamine
Additional Notes Colour Pages: 25, 37, 64, 85, 93, 112, 135, 136, 137

 
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Created: Tue, 24 May 2011, 21:28:16 EST by Mr Michael Somerville on behalf of Library - Information Access Service