Structural and synthetic investigations of diterpenoid natural products from southern African marine invertebrates
- Authors: Gray, Christopher Anthony
- Date: 2003
- Subjects: Ethyl acetoacetate Diterpenes Limpets -- South Africa Natural products -- South Africa
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4349 , http://hdl.handle.net/10962/d1005014
- Description: This thesis is divided into two parts. The first part (Chapter Two) documents a bioassay guided investigation of the ethyl acetate extracts of four marine invertebrates from Mozambique (an Irciniid sponge, a Haliclona sp. sponge, an ascidian tentatively identified as Diplosoma sp., and the soft coral Cladiella kashmani). Eight known compounds [ilimaquinone (2.1), renierone (2.7), N-formyl-1,2-dihydrorenierone (2.8), 1,6-dimethyl-7-methoxy-5,8-dihydroisoquinoline-5,8-dione (2.9), mimosamycin (2.10) 7Z-allylidene-5-hydroxy-7,7a-dihydro-2H-cyclopenta[b]pyran-6-one (2.11), flaccidoxide (2.18) and 11S,12S-epoxycembra-1Z,3E,7E-trien-14S-ol (2.19)] and a new diterpene [13S,14R-diacetoxy-11S,12R-epoxycembra-1Z,3E,7E-triene (2.20)] were isolated and identified using standard spectroscopic techniques. Anomalies in the published spectral data of 2.1 and 2.8 were exposed and corrected, and the absolute stereochemistry of the cembrane diterpenes 2.18 and 2.20 established using the modified Mosher’s method. The comparative activities of the nine natural products against four cancer cell lines (A549, LOX, OVCAR3, SNB19) are reported. The second part of the thesis (Chapter Three – Chapter Six) is concerned with an ecological, structural and synthetic study of diterpenes from the endemic South African pulmonate limpet Trimusculus costatus. Two new labdane diterpenes [6b,7a-diacetoxylabda-8,13E-dien-15-ol (3.10) and 2a,6b,7a-triacetoxylabda-8,13E-dien-15-ol (3.11)] were isolated from T. costatus and evaluated for anti-feeding activity against the common predatory fish Pomadasys commersonnii. A strategy for the semi-synthesis of 3.10 from rhinocerotinoic acid (4.14), a diterpene reportedly present in the ubiquitous South African shrub Elytropappus rhinocerotis, was devised in order to allow further bioactivity tests to be performed and unequivocally assign the unknown absolute stereochemistry of the T. costatus metabolites. Attempts to isolate rhinocerotinoic acid from local specimens of Elytropappus rhinocerotis were unsuccessful, and as the repetition of a published synthesis of 4.14 from (-)-sclareol (4.15) gave rhinocerotinoic acid in unacceptably low yields with poor stereoselectivity, an improved synthesis of 4.14 is presented. Comprehensive studies using hispanone (5.1) as a model compound showed that 6,7-dioxygenated labda-8-enes could be prepared from compounds possessing a 7-oxo-labda-8-ene skeleton with some degree of stereocontrol. In the process, fourteen new hispanone analogues were prepared and most of these were tested for activity in a suite of ten agro-chemical assays. The novel compound 7b-hydroxy-9a-carbonitrile-15,16-epoxylabda-13(16),14-dien-6-one (5.34) exhibited significant activity against the crop fungus Phytophthora infestans and is currently being subjected to further agro-chemical tests. Unfortunately, the results from the oxygenation study performed on the model compound 5.1 could not be directly extrapolated to rhinocerotinoic acid. Attempts to prepare the naturally occurring 3.10 from 4.14 via an alternative route were unsuccessful but yielded an analogue of 3.10 in which the substituents at C-6 and C-7 are in a diequatorial rather than a diaxial configuration.
- Full Text:
- Date Issued: 2003
- Authors: Gray, Christopher Anthony
- Date: 2003
- Subjects: Ethyl acetoacetate Diterpenes Limpets -- South Africa Natural products -- South Africa
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4349 , http://hdl.handle.net/10962/d1005014
- Description: This thesis is divided into two parts. The first part (Chapter Two) documents a bioassay guided investigation of the ethyl acetate extracts of four marine invertebrates from Mozambique (an Irciniid sponge, a Haliclona sp. sponge, an ascidian tentatively identified as Diplosoma sp., and the soft coral Cladiella kashmani). Eight known compounds [ilimaquinone (2.1), renierone (2.7), N-formyl-1,2-dihydrorenierone (2.8), 1,6-dimethyl-7-methoxy-5,8-dihydroisoquinoline-5,8-dione (2.9), mimosamycin (2.10) 7Z-allylidene-5-hydroxy-7,7a-dihydro-2H-cyclopenta[b]pyran-6-one (2.11), flaccidoxide (2.18) and 11S,12S-epoxycembra-1Z,3E,7E-trien-14S-ol (2.19)] and a new diterpene [13S,14R-diacetoxy-11S,12R-epoxycembra-1Z,3E,7E-triene (2.20)] were isolated and identified using standard spectroscopic techniques. Anomalies in the published spectral data of 2.1 and 2.8 were exposed and corrected, and the absolute stereochemistry of the cembrane diterpenes 2.18 and 2.20 established using the modified Mosher’s method. The comparative activities of the nine natural products against four cancer cell lines (A549, LOX, OVCAR3, SNB19) are reported. The second part of the thesis (Chapter Three – Chapter Six) is concerned with an ecological, structural and synthetic study of diterpenes from the endemic South African pulmonate limpet Trimusculus costatus. Two new labdane diterpenes [6b,7a-diacetoxylabda-8,13E-dien-15-ol (3.10) and 2a,6b,7a-triacetoxylabda-8,13E-dien-15-ol (3.11)] were isolated from T. costatus and evaluated for anti-feeding activity against the common predatory fish Pomadasys commersonnii. A strategy for the semi-synthesis of 3.10 from rhinocerotinoic acid (4.14), a diterpene reportedly present in the ubiquitous South African shrub Elytropappus rhinocerotis, was devised in order to allow further bioactivity tests to be performed and unequivocally assign the unknown absolute stereochemistry of the T. costatus metabolites. Attempts to isolate rhinocerotinoic acid from local specimens of Elytropappus rhinocerotis were unsuccessful, and as the repetition of a published synthesis of 4.14 from (-)-sclareol (4.15) gave rhinocerotinoic acid in unacceptably low yields with poor stereoselectivity, an improved synthesis of 4.14 is presented. Comprehensive studies using hispanone (5.1) as a model compound showed that 6,7-dioxygenated labda-8-enes could be prepared from compounds possessing a 7-oxo-labda-8-ene skeleton with some degree of stereocontrol. In the process, fourteen new hispanone analogues were prepared and most of these were tested for activity in a suite of ten agro-chemical assays. The novel compound 7b-hydroxy-9a-carbonitrile-15,16-epoxylabda-13(16),14-dien-6-one (5.34) exhibited significant activity against the crop fungus Phytophthora infestans and is currently being subjected to further agro-chemical tests. Unfortunately, the results from the oxygenation study performed on the model compound 5.1 could not be directly extrapolated to rhinocerotinoic acid. Attempts to prepare the naturally occurring 3.10 from 4.14 via an alternative route were unsuccessful but yielded an analogue of 3.10 in which the substituents at C-6 and C-7 are in a diequatorial rather than a diaxial configuration.
- Full Text:
- Date Issued: 2003
The role of a symbiotic bryozoan in the chemical ecology of a marine benthic predator-prey interaction
- Authors: Gray, Christopher Anthony
- Date: 2001
- Subjects: Marine animals , Marine ecology , Benthic animals
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:5756 , http://hdl.handle.net/10962/d1005444 , Marine animals , Marine ecology , Benthic animals
- Description: The subtidal whelk Burnupena papyracea (Brugière) co-occurs with a voracious predator, the rock lobster Jasus lalandii (Milne Edwards), in situations where other potential prey are largely eliminated. This has been ascribed to a symbiotic bryozoan, Alcyonidium nodosum (O’Donoghue and de Watteville), which characteristically encrusts the shells of B. papyracea and deters feeding by Jasus. In this study it is shown that this is not due to physical effects of either induced physical defences in the bryozoan or increased shell strength due to the presence of the bryozoan. Neither spectroscopic screening of chemical extracts of the bryozoan nor analysis for volatile constituents revealed any apparent chemical components that are likely to deter feeding. Chemical extracts also failed to show larvicidal effects in a standard toxicity assay using the brine shrimp Artemia salina (Leach). Despite this, bioassays using individual Jasus indicated a chemical basis for feeding deterrence. The assays were run separately on three sets of Jasus and some repeats of assays gave contradictory results. However, assays showing no significant effect of treatment occurred with moulting Jasus, involved very low overall feeding rates and so gave a less convincing result. In other assays Jasus always avoided Burnupena papyracea with live Alcyonidium encrusting the shell, and food pellets containing Alcyonidium or an Alcyonidium extract. Significant preferences were shown for an unencrusted whelk, B. cincta (Röding), over B. papyracea; for B. papyracea with the bryozoan scraped off over natural B. papyracea; for B. papyracea on which the bryozoans had been killed with liquid nitrogen over untreated B. papyracea; and for food pellets prepared from ground, dried mussel over pellets prepared with dried mussel mixed with A. nodosum or its crude organic extract. It is concluded that the protection which Alcyonidium confers on Burnupena papyracea does have a chemical basis, but that the chemical responsible is either present in only trace quantities, or that it is a structurally unremarkable compound which is distasteful to Jasus. This work highlights both the advantages of using ecologically relevant bioassays (positive results when standard techniques give a negative result) and also the disadvantages (logistic constraints on sample sizes when using large test animals and individual variability in a relatively sophisticated test animal).
- Full Text:
- Date Issued: 2001
- Authors: Gray, Christopher Anthony
- Date: 2001
- Subjects: Marine animals , Marine ecology , Benthic animals
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:5756 , http://hdl.handle.net/10962/d1005444 , Marine animals , Marine ecology , Benthic animals
- Description: The subtidal whelk Burnupena papyracea (Brugière) co-occurs with a voracious predator, the rock lobster Jasus lalandii (Milne Edwards), in situations where other potential prey are largely eliminated. This has been ascribed to a symbiotic bryozoan, Alcyonidium nodosum (O’Donoghue and de Watteville), which characteristically encrusts the shells of B. papyracea and deters feeding by Jasus. In this study it is shown that this is not due to physical effects of either induced physical defences in the bryozoan or increased shell strength due to the presence of the bryozoan. Neither spectroscopic screening of chemical extracts of the bryozoan nor analysis for volatile constituents revealed any apparent chemical components that are likely to deter feeding. Chemical extracts also failed to show larvicidal effects in a standard toxicity assay using the brine shrimp Artemia salina (Leach). Despite this, bioassays using individual Jasus indicated a chemical basis for feeding deterrence. The assays were run separately on three sets of Jasus and some repeats of assays gave contradictory results. However, assays showing no significant effect of treatment occurred with moulting Jasus, involved very low overall feeding rates and so gave a less convincing result. In other assays Jasus always avoided Burnupena papyracea with live Alcyonidium encrusting the shell, and food pellets containing Alcyonidium or an Alcyonidium extract. Significant preferences were shown for an unencrusted whelk, B. cincta (Röding), over B. papyracea; for B. papyracea with the bryozoan scraped off over natural B. papyracea; for B. papyracea on which the bryozoans had been killed with liquid nitrogen over untreated B. papyracea; and for food pellets prepared from ground, dried mussel over pellets prepared with dried mussel mixed with A. nodosum or its crude organic extract. It is concluded that the protection which Alcyonidium confers on Burnupena papyracea does have a chemical basis, but that the chemical responsible is either present in only trace quantities, or that it is a structurally unremarkable compound which is distasteful to Jasus. This work highlights both the advantages of using ecologically relevant bioassays (positive results when standard techniques give a negative result) and also the disadvantages (logistic constraints on sample sizes when using large test animals and individual variability in a relatively sophisticated test animal).
- Full Text:
- Date Issued: 2001
- «
- ‹
- 1
- ›
- »