The objective of this Ph.D research was to investigate the secondary metabolite composition of sponges and nudibranchs from South-East Queensland, Australia and Bali, Indonesia. Three different species of sponges and five species of nudibranchs were collected by hand using SCUBA on several diving occasions between 2010 and 2012. Isolation and purification of the secondary metabolites was achieved by means of flash chromatography on silica gel as well as by high performance liquid chromatography (HPLC). Structure elucidation of the isolated compounds was accomplished by assorted spectral methods including various 1D and 2D nuclear magnetic resonance (NMR) techniques, mass spectrometry (MS), electronic circular dichroism (ECD), chemical derivatisation and total synthesis. Antimalarial evaluations of selected metabolites were performed against chloroquine-sensitive P. falciparum parasites.
Chemical investigation of an organic extract of the Balinese sponge Aplysinella strongylata led to the isolation of bromotyrosine metabolites of the psammaplysin series including twenty one new derivatives and six known compounds. The structures of the new metabolites were grouped into those containing modified side chains (2.38-2.42) as well as straight chain, iso or anteiso branched chains, and some with monoenoic fatty acid (2.43-2.55, 2.58-2.60) side chains. Absolute configuration determination at C-6 and C-7 of the psammaplysin series is being carried out by comparing the ECD profile of psammaplysin A (2.11) obtained from experiment with the profile of calculated from theoretical data. Among the selected samples tested for antimalarial properties, 19 hydroxypsammaplysin E (2.38) displayed modest in vitro growth inhibition towards chloroquine-sensitive P. falciparum parasites with an IC50 value of 6.4 µM. Another Balinese sponge, Theonella sp., yielded three known theonellapeptolides Ib (5.11), Ib (5.13), Id (5.14) that were identified on the basis of the comparison of their spectroscopic data with those published in the literature; antimalarial bioassay on these metabolites is underway.
A study on populations of three Hypselodoris species including H. obscura, H. jacksoni, and H. whitei obtained near Mudjimba Island and the Gold Coast returned seven known furanosesquiterpenes (3.8-3.9, 3.30-3.33) together with a new enantiomer of (+)-agassizin (3.29) as well as a new 5-acetate derivative of dendrolasin (3.34). The isolation of these metabolites in the current work expands the occurrence of furanosesquiterpenes in Hypselodoris nudibranchs obtained from South-East Queensland, Australia. Owing to the limited amount of metabolite 3.34 isolated from the extract of H. jacksoni, a total synthesis was completed to obtain sufficient material for absolute configuration determination at C-5. The targeted compound was prepared in a five-step synthesis involving [1,2]-Wittig rearrangement of geranylfuryl ether (3.45) followed by acetylation of the purified alcohol products (3.46b). The absolute configuration of 3.34 was established as 5R by detailed comparison with MPA ester derivatives prepared from individual enantiomers of synthetic (6Z)-5-hydroxy dendrolasin purified by preparative enantioselective HPLC.
A Balinese specimen of G. hikeurensis yielded exclusively scalarane sesterterpenes, including five known scalaranes (4.17-4.18, 4.42-4.44), the new 19-acetyl-12-deacetyl-12-epi-deoxoscalarin (4.45), and a new scalarane 4.46. To the best of our knowledge, this is the first chemical study carried out on a Balinese nudibranch. A single specimen of Glossodoris atromarginata obtained near Mudjimba Island South-East Queensland returned a group of norsesterterpene metabolites, including the known mooloolabene F (4.22), mooloolaldehyde (4.53), and mooloolabene D (4.54). In addition, two new derivatives alphabetically named as mooloolabenes O (4.52) and P (4.55) were also characterised. The chemistry of the prey-predator relationship between nudibranch Goniobranchus albonares and an encrusting crimson sponge is presented. The extracts of each nudibranch and sponge contained the known diterpene dendrillolide A (4.56), while a new 12 acetoxy dendrillolide A (4.58) was identified from the extract of the sponge prey along with aplyviolene (4.57). Furthermore, the diterpene macfarlandin E (4.38) was isolated as a minor component of the Et2O extract of G. albonares. This is the first chemical study on the nudibranch G. albonares and its associated sponge prey.