Studies in marine natural products
Degree GrantorUniversity of Canterbury
Degree NameDoctor of Philosophy
The marine environment continues to be a prolific source of structurally diverse and biologically active natural products. Over the past few decades both macroand micro-organisms have been extensively studied for such compounds. Annual reviews are dominated by novel compounds isolated from marine sponges, even though investigations have more recently been focused on micro-organisms. After decades of research into the development of marine natural products as potential pharmaceuticals, many marine compounds now feature prominently in current pre-clinical and clinical trials. This thesis represents a continuation of work in the area of isolation and structural elucidation of novel and/or biologically active natural products from both marine macro- and micro-organisms.
The four novel C₃₁ polyacetylenic compounds 2.23, 2.24, 2.25 and 2.26 were isolated as the major components of the cytotoxic extract of the New Zealand marine sponge Rhabderemia stelletta, using bioassay-guided separation techniques. However, these structures were not unambiguously assigned due to the low resolution of the NMR signals associated with the long-chain alkyl protons and carbons. Elucidation was also hindered by compound degradation during structural analysis. The partial structures were identified via mass spectrometry and NMR spectroscopy and comparison of structural data for similar compounds reported in the literature. The novel pteridines 3.13 and 3.15 were isolated as the major and minor components, respectively, from the cytotoxic organic extract of an as yet unidentified Antarctic marine sponge 02WM01-33. Identification was achieved using mass spectrometry and NMR spectroscopy, and comparison of these data to those published in the literature for similar structures. Although pteridines are distributed widely throughout nature, 3.13 and 3.15 represent a chemically interesting group of compounds as they possess a mono-oxygenated methyl side chain, which has not been previously reported among any of the naturally occurring pteridines. The novel hydantoin compound 4.8 was isolated as the major biologically active component of the organic extract of the Antarctic marine sponge Suberites sp. using microtitre plate P388 assay guided fractionation. The relative stereochemistry of 4.8 was determined using lD-NOESY experimental data. This work represents the first isolation of the hydantoin 4.8 as a natural product from a marine sponge. This compound has been reported previously in the literature, but only as a synthetic product. The two novel anthraquinone compounds 5.35 and 5.41 were isolated as minor components of the cytotoxic organic extract of the Antarctic marine spongederived fungus Aspergillus sp., along with the three known anthraquinones 5.32, 5.34 and 5.40. This series of work revealed several areas in the literature that require revising: these include, (i) the compounds 5.31 and 5.41 were both reported as a new metabolites in 1985 and 2003, respectively, however, both compounds had been previously isolated and reported in 1966; (ii) the compound 5.36 requires the correct structural assignment in the literature; and finally, (iii) the compound 5.35 has two isomeric structures reported in the AntiMarin database, however, neither of these structures match the experimental ¹H NMR data supplied by the author of the database. The three novel compounds 6.9, 6.13 and 6.15 were isolated from the organic extract of an Antarctic marine sponge-derived fungus Ulocladuim sp., along with the previously reported compounds 6.6, 6.7 and 6.16. These compounds were identified using NMR spectroscopy and mass spectrometry. This work highlights an inconsistency in the literature regarding the structural assignment of two carbons for the known compound 6.16. The structural assignment of these carbons was confirmed by the independent isolation of 6.16 by another member of the Marine Group.