3 results for Doctoral, Studies in marine natural products

  • Studies in marine natural products

    Prinsep, Michéle (1990)

    Doctoral thesis
    University of Canterbury Library

    Two new β-carboline alkaloids were isolated from the bryozoan Cribricellina cribraria. One of these, 1-vinyl-8-hydroxy-β-carboline, was the major cytotoxic component of the extract, while the other had a novel sulphone structure. Several other known β-carboline alkaloids were also isolated from the extract. To investigate structure-activity relationships in these compounds, several derivatives of the major alkaloid were prepared and a number of 1-substituted β-carboline alkaloids synthesised. Nmr spectroscopic studies of these compounds were carried out and previously published ¹³C nmr data for some of these compounds revised. Homarine was isolated as the major water soluble component of the extract and the sterol composition examined. Known β-carboline alkaloids were isolated from the related bryozoan Margaretta barbata. The known biologically active compounds, girolline and hymenialdisine were isolated from the sponge Axinella sp. 2. As some discrepancies between the experimental and published data on hymenialdisine were noted, an X-ray crystal structure analysis was performed. Oroidin, homarine and taurine were also isolated from the extract and the sterol composition found to consist exclusively of ring-contracted A norstanols. An extract of the sponge Stylopus australis was found to contain a new sterol sulphate and two derivatives of this compound were prepared. The full assignment of the ¹H nmr spectrum of the sulphate was achieved with the aid of COSY, nOe, HETCOR and XCORFE nmr experiments. The glyceryl ether, chimyl alcohol was also isolated from the sponge. An extract of the related sponge, Hymedesmia sp. 1 was examined and rhodoic acid isolated as the major water soluble component, along with homarine. The sterol compositions of Stylopus australis and Hymedesmia species 1 and 2 were examined for comparative purposes. Studies on an extract of the sponge Hymeniacidon hauraki led to the isolation of a new furan fatty acid. The sterol corbisterol and its peroxide were isolated from one sample of the sponge and this led to an examination of infraspecific sterol variation in this species. A screening procedure of biologically active natural product extracts has been developed. The procedure involves examining the chromatographic behaviour of the biological activity of an extract and is designed to detect known biologically active compounds and to determine the best means of handling extracts containing unknown biologically active components.

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  • Studies in marine natural products

    MacLean, Warren Jon (2005)

    Doctoral thesis
    University of Canterbury Library

    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.

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  • Studies in marine natural products

    Barrow, Colin James (1988)

    Doctoral thesis
    University of Canterbury Library

    The bioactivity directed analysis of the extract from a sponge of the genus Sarcotragus led to the isolation of a series of bioactive sesterterpenes, of which variabilin (1a) was the major component. The sesterterpenes (29a), (30) and (31a), along with the related C₂₁ furanoterpene (32), were present in lesser amounts. The unequivocal assignment of the stereochemistry of the 20,21 double bond in variabilin as 20(Z) was achieved through examination of the22-O-methyl derivative (1b) of variabilin and the isolation of the variabilin isomer (29a) with the 20(E) stereochemistry. Variabilin was also isolated from a sponge of the genus lrcinia. The four related bioactive sesterterpenes (33b), (34b), (35b), and (36b) together with (31b) were isolated from a methylated extract from the same sponge. Variabilin autooxidised in the presence of light and air to form a mixture of products that underwent further oxidation on standing. The 22-O-methyl derivative (1b) of variabilin did not autooxidize but underwent oxidation in the presence of the singlet oxygen sensitizer, rose bengal. The products from this oxidation reaction were (48b), (49b), (50b), (51b), (52b), (53b), (50b), (61b), (62b), (63b), (64b) and (65b) and these were the same as the products from the variabilin autooxidation with the exception of the methyl group at C₂₂. Variabilin autooxidation was shown to occur through the production of singlet oxygen and subsequent oxygen addition to the furan moiety. The production of singlet oxygen occurred through a sensitization mechanism involving the variabilin tetronic acid moiety. To investigate structure-bioactivity relationships in variabilin and related sesterterpenes, derivatization of the furan and tetronic acid moieties in variabilin was carried out. 22-O-Me variabilin (1b), in contrast to variabilin, reacted favourably under most furan reaction conditions and so a number of reactions were carried out on (1b) also. Hydrogenation of variabilin gave the cytotoxic compound (73). Dials-Alder addition of DMAD to variabilin gave the cytotoxic compounds (74a) and (75a) and acylation gave the cytotoxic compounds (81) and (82). Reduction of these acylation products gave the cytotoxic derivatives (83) and (84). The non-cytotoxic compound (85) was formed on reaction of p-bromobenzoylchloride with variabilin. Dials-Alder addition of DMAD to 22-O-Me variabilin gave the cytotoxic compounds (74b) and (75b) and addition of 4-phenyl-1,2,4-triazoline-3,5-dione (phenyl-TD) (78) gave the potential antiviral compounds (76) and (77). A cytotoxic sesquiterpene (86) with a tricyclo[6.3.1.0.²,⁵]dodecane skeleton has been isolated from the extract of a New Zealand Eurypon sp. of sponge. Two derivatives, (87) and (88), of this sesquiterpene have also been isolated, probably as artefacts arising during the isolation procedure. The structure of a spirosesquiterpene (89), also obtained from the sponge extract, has been determined. Previously published nmr assignments for β-caryophyllene alcohol (90) have been revised. Three further compounds, labeled unknowns a-c, were isolated, but their structures were not determined. One of these unknowns (unknown a) was probably a sesquiterpene, and was shown to be cytotoxic, while the remaining two (unknowns band c) gave spectroscopic data which indicated that while they were very closely related to one another, they were not sesquiterpenes. Bioassay directed isolations of the active components from a new sponge, genus Chondropsis, and the bryozoan, Margaretta barbata, were attempted. The bryozoan, Margaretta barbata had previously been shown to exhibit significant in vivo P388 activity. For the Chondropsis species the components responsible for the observed biological activity appeared to be very minor components of the overall sponge and isolation of the active compounds was not achieved. For the bryozoan the more polar active material was present in reasonable abundance and a compound (unknown d) giving in vitro P388 activity was isolated. However full characterisation of this compound was not achieved. The compound, or compounds, responsible for the biological activity shown by the less polar material were not isolated. Sterols were shown to be major components of the non-polar organic material in both the sponge and bryozoan species studied. For the Chondropsis sponge the major sterol component was identified as 24-methylene-cholesterol (92). For the bryozoan, Margaretta barbata, the major sterol was identified as cholesterol (93) with 24-methylene-cholesterol (92) and cholest-4-en-3-one (94) also being identified. The major organic water soluble compound was identified as homarine (95).

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