Studies in South African marine molluscan chemistry
- Authors: Bromley, Candice Leigh
- Date: 2011
- Subjects: Mollusks -- South Africa , Marine invertebrates -- South Africa , Marine metabolites -- South Africa , Chemical oceanography -- South Africa
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:4356 , http://hdl.handle.net/10962/d1005021
- Description: This thesis investigates the variability occurring in the secondary metabolites produced by three South African marine molluscs. Chapter Two discusses the isolation and spectroscopic structure elucidation of the metabolites isolated from two Siphonaria species. The re-investigation of Siphonaria capensis yielded siphonarienfuranone (2.2) as the only common polypropionate isolated from both the 1998 and 2009 collections of S. capensis from the same areas suggesting possible seasonal or genetic variation in polypropionate production. The sterol cholest-7-en-3,5,7- triol (2.33) was also isolated form the 2009 collection of S. capensis and this is the first time this compound has been isolated from a Siphonaria species. The second species, Siphonaria oculus is closely related to S. capensis and the investigation into the former’s secondary metaboliteproduction revealed 2.2 as a major metabolite suggesting an inter-species overlap in polypropionate production. Three new polypropionate metabolites, 2.35, 2.36 and 2.37 were also isolated from S. oculus. An unsuccessful attempt was made to establish the absolute configuration of 2.37 using the modified Mosher’s method and the limited amount of 2.37 available prevented any further attempts at resolving the absolute configuration of this compound. The 1H NMR analysis of the defensive mucus collected directly from S. oculus revealed the presence of the acyclic polypropionate 2.37 as a minor metabolite. The absence of characteristic signals for the furanone containing compounds 2.2, 2.35 and 2.36, might suggest that these compounds cyclise from a hypothetical acyclic precursor (2.38) during standard work up of bulk acetone extracts of Siphonaria species. Chapter Three discusses the re-isolation and spectroscopic structure elucidation of the metabolites isolated from the nudibranch, Leminda millecra. Three known natural products, millecrone A (3.1), 8-hydroxycalamenene (3.6) and cubebenone (3.8) were re-isolated from our 2010 collection of L. millecra, as well as the new minor metabolite 8-acetoxycalamenene (3.16). The cytotoxic prenylated toluquinones and toluhydroquinones (3.9-3.15) initially isolated from the 1998 collection of L. millecra were not found in the 2010 collection supporting the hypothesis that these compounds may be of fungal origin. L. millecra clearly shows variability in the compounds sequestered by this species with millecrone A (3.1) being the only common metabolite in the three investigations of L. millecra to date. An unsuccessful attempt was made to establish the absolute configuration of 3.1, 3.6 and 3.8 through initial LAH reduction of the ketone moiety contained in 3.1 and 3.8 and esterification of the resultant diastereomeric alcohol mixtures and the phenol functionality in 3.6 with (1S)-camphanic chloride. Crystallisation of the (S)- camphanate esters of 3.6 and 3.8 for X-ray analysis were unsuccessful, while the unexpected conjugate addition of a hydride in 3.1 resulted in complex diastereomeric mixtures which could not be separated by HPLC.
- Full Text:
- Date Issued: 2011
- Authors: Bromley, Candice Leigh
- Date: 2011
- Subjects: Mollusks -- South Africa , Marine invertebrates -- South Africa , Marine metabolites -- South Africa , Chemical oceanography -- South Africa
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:4356 , http://hdl.handle.net/10962/d1005021
- Description: This thesis investigates the variability occurring in the secondary metabolites produced by three South African marine molluscs. Chapter Two discusses the isolation and spectroscopic structure elucidation of the metabolites isolated from two Siphonaria species. The re-investigation of Siphonaria capensis yielded siphonarienfuranone (2.2) as the only common polypropionate isolated from both the 1998 and 2009 collections of S. capensis from the same areas suggesting possible seasonal or genetic variation in polypropionate production. The sterol cholest-7-en-3,5,7- triol (2.33) was also isolated form the 2009 collection of S. capensis and this is the first time this compound has been isolated from a Siphonaria species. The second species, Siphonaria oculus is closely related to S. capensis and the investigation into the former’s secondary metaboliteproduction revealed 2.2 as a major metabolite suggesting an inter-species overlap in polypropionate production. Three new polypropionate metabolites, 2.35, 2.36 and 2.37 were also isolated from S. oculus. An unsuccessful attempt was made to establish the absolute configuration of 2.37 using the modified Mosher’s method and the limited amount of 2.37 available prevented any further attempts at resolving the absolute configuration of this compound. The 1H NMR analysis of the defensive mucus collected directly from S. oculus revealed the presence of the acyclic polypropionate 2.37 as a minor metabolite. The absence of characteristic signals for the furanone containing compounds 2.2, 2.35 and 2.36, might suggest that these compounds cyclise from a hypothetical acyclic precursor (2.38) during standard work up of bulk acetone extracts of Siphonaria species. Chapter Three discusses the re-isolation and spectroscopic structure elucidation of the metabolites isolated from the nudibranch, Leminda millecra. Three known natural products, millecrone A (3.1), 8-hydroxycalamenene (3.6) and cubebenone (3.8) were re-isolated from our 2010 collection of L. millecra, as well as the new minor metabolite 8-acetoxycalamenene (3.16). The cytotoxic prenylated toluquinones and toluhydroquinones (3.9-3.15) initially isolated from the 1998 collection of L. millecra were not found in the 2010 collection supporting the hypothesis that these compounds may be of fungal origin. L. millecra clearly shows variability in the compounds sequestered by this species with millecrone A (3.1) being the only common metabolite in the three investigations of L. millecra to date. An unsuccessful attempt was made to establish the absolute configuration of 3.1, 3.6 and 3.8 through initial LAH reduction of the ketone moiety contained in 3.1 and 3.8 and esterification of the resultant diastereomeric alcohol mixtures and the phenol functionality in 3.6 with (1S)-camphanic chloride. Crystallisation of the (S)- camphanate esters of 3.6 and 3.8 for X-ray analysis were unsuccessful, while the unexpected conjugate addition of a hydride in 3.1 resulted in complex diastereomeric mixtures which could not be separated by HPLC.
- Full Text:
- Date Issued: 2011
Marine biotechnology : evaluation and development of methods for the discovery of natural products from fungi
- Authors: Pather, Simisha
- Date: 2005 , 2013-06-18
- Subjects: Marine biotechnology , Marine fungi -- South Africa , Natural products -- South Africa , Marine plants -- South Africa , Marine metabolites -- South Africa , Cancer -- Treatment , DNA
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3839 , http://hdl.handle.net/10962/d1007652 , Marine biotechnology , Marine fungi -- South Africa , Natural products -- South Africa , Marine plants -- South Africa , Marine metabolites -- South Africa , Cancer -- Treatment , DNA
- Description: One of the major impediments in the development of marine natural products is the provision of biologically active natural products in sufficient quantity for complete pharmacological evaluation, clinical trials and eventual commercial production. Marine microorganisms show great promise in providing a renewable source of biologically active natural products. The main aim of this study was to develop and evaluate methods for the isolation, identification and cultivation of marine fungi from the South African marine environment for the production of biologically active secondary metabolites. Twenty-four species of fungi were isolated from marine algae collected from the intertidal zone near Port Alfred, South Africa. The fungi were cultivated in small-scale under static and agitated conditions and their crude intra- and extracellular organic extracts were screened by ¹H NMR and a series of bioassays. Using this as a basis, one isolate was selected for further study. By analyses of the lTS1 region of the ribosomal DNA, the fungal isolate was identified as a marine-derived isolate of Eurotium rubrum (Aspergillus ruber). Although E. rubrum has been isolated from the marine environment, no investigations have been undertaken to determine the adaptation of these isolates to the marine environment. In order to optimise productivity, creativity and incubation time, the fungus was cultivated in small-scale using a variety of carbon (glucose, fructose, lactose, sucrose, marmitol and maltose) and nitrogen sources (ammonium tartrate, urea, peptone and yeast extract). An HPLC-DAD method was developed to assess the metabolic creativity and productivity under different fermentation conditions. Distinctive variations in the range and yield of metabolites produced as well as morphology and growth time were observed. The crude extracts from all fermentations were combined and six known compounds were isolated by reversed-phase chromatography and their structures elucidated by spectroscopic techniques. The known compounds were fIavoglaucin, aspergin, isodihydroauroglaucin, isotetrahydroauroglaucin, neoechinuline A and physcion. Neoechinuline A, isodihydroauroglaucin and isotetrahydroauroglaucin showed activity against oesophageal and cervical cancer cell lines.
- Full Text:
- Date Issued: 2005
- Authors: Pather, Simisha
- Date: 2005 , 2013-06-18
- Subjects: Marine biotechnology , Marine fungi -- South Africa , Natural products -- South Africa , Marine plants -- South Africa , Marine metabolites -- South Africa , Cancer -- Treatment , DNA
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3839 , http://hdl.handle.net/10962/d1007652 , Marine biotechnology , Marine fungi -- South Africa , Natural products -- South Africa , Marine plants -- South Africa , Marine metabolites -- South Africa , Cancer -- Treatment , DNA
- Description: One of the major impediments in the development of marine natural products is the provision of biologically active natural products in sufficient quantity for complete pharmacological evaluation, clinical trials and eventual commercial production. Marine microorganisms show great promise in providing a renewable source of biologically active natural products. The main aim of this study was to develop and evaluate methods for the isolation, identification and cultivation of marine fungi from the South African marine environment for the production of biologically active secondary metabolites. Twenty-four species of fungi were isolated from marine algae collected from the intertidal zone near Port Alfred, South Africa. The fungi were cultivated in small-scale under static and agitated conditions and their crude intra- and extracellular organic extracts were screened by ¹H NMR and a series of bioassays. Using this as a basis, one isolate was selected for further study. By analyses of the lTS1 region of the ribosomal DNA, the fungal isolate was identified as a marine-derived isolate of Eurotium rubrum (Aspergillus ruber). Although E. rubrum has been isolated from the marine environment, no investigations have been undertaken to determine the adaptation of these isolates to the marine environment. In order to optimise productivity, creativity and incubation time, the fungus was cultivated in small-scale using a variety of carbon (glucose, fructose, lactose, sucrose, marmitol and maltose) and nitrogen sources (ammonium tartrate, urea, peptone and yeast extract). An HPLC-DAD method was developed to assess the metabolic creativity and productivity under different fermentation conditions. Distinctive variations in the range and yield of metabolites produced as well as morphology and growth time were observed. The crude extracts from all fermentations were combined and six known compounds were isolated by reversed-phase chromatography and their structures elucidated by spectroscopic techniques. The known compounds were fIavoglaucin, aspergin, isodihydroauroglaucin, isotetrahydroauroglaucin, neoechinuline A and physcion. Neoechinuline A, isodihydroauroglaucin and isotetrahydroauroglaucin showed activity against oesophageal and cervical cancer cell lines.
- Full Text:
- Date Issued: 2005
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