From frontier to midlands: a history of the Graaff-Reinet district, 1786-1910
- Authors: Smith, Kenneth Wyndham
- Date: 1976
- Subjects: Graaff-Reinet (South Africa) -- History
- Language: English
- Type: Book , Text
- Identifier: http://hdl.handle.net/10962/2656 , vital:20313 , ISBN 0949980730
- Description: The study of local history in South Africa is still in its infancy and has not been accorded the same recognition as elsewhere. There is no convenient manual to guide the would-be local historian of the Cape. There are few models that provide an insight into the main problems encountered by the local historian of a Cape community. In such local histories as exist, attention has been focussed predominantly on the foundation and physical growth of towns, the naming of streets, the establishment of schools and hospitals. Many of these accounts were written for publicity purposes or to commemorate the founding of towns. Although there is no history of the Dutch Reformed Church in Graaff-Reinet, the history of local congregations of the Dutch Reformed Church has generally been well covered in the form of Gedenkboeke and other studies. These frequently have a particular relevance as many towns such as Burgersdorp and Colesberg were founded as a result of the initiative of the church. Preface. , Digitised by Rhodes University Library on behalf of the Institute of Social and Economic Research (ISER)
- Full Text:
- Date Issued: 1976
- Authors: Smith, Kenneth Wyndham
- Date: 1976
- Subjects: Graaff-Reinet (South Africa) -- History
- Language: English
- Type: Book , Text
- Identifier: http://hdl.handle.net/10962/2656 , vital:20313 , ISBN 0949980730
- Description: The study of local history in South Africa is still in its infancy and has not been accorded the same recognition as elsewhere. There is no convenient manual to guide the would-be local historian of the Cape. There are few models that provide an insight into the main problems encountered by the local historian of a Cape community. In such local histories as exist, attention has been focussed predominantly on the foundation and physical growth of towns, the naming of streets, the establishment of schools and hospitals. Many of these accounts were written for publicity purposes or to commemorate the founding of towns. Although there is no history of the Dutch Reformed Church in Graaff-Reinet, the history of local congregations of the Dutch Reformed Church has generally been well covered in the form of Gedenkboeke and other studies. These frequently have a particular relevance as many towns such as Burgersdorp and Colesberg were founded as a result of the initiative of the church. Preface. , Digitised by Rhodes University Library on behalf of the Institute of Social and Economic Research (ISER)
- Full Text:
- Date Issued: 1976
A socio-economic survey of the Amatola Basin: interim report
- Bekker, S B, de Wet, Christopher J, Manona, Cecil W
- Authors: Bekker, S B , de Wet, Christopher J , Manona, Cecil W
- Date: 1981
- Subjects: Ciskei (South Africa) -- Rural conditions Agriculture -- South Africa -- Ciskei Middledrift (South Africa) Fingo (African people) Hlubi (African people) Agriculture -- South Africa -- Ciskei Amatola River Watershed (South Africa) -- Economic conditions Amatola River Watershed (South Africa) -- Social conditions
- Language: English
- Type: Book , Text
- Identifier: http://hdl.handle.net/10962/2282 , vital:20272 , ISBN 0868100730
- Description: Early in 1981, Professor S. Bekker of Rhodes University was invited to attend a meeting of the Amatola Basin Steering Committee of the Agricultural and Rural Development Research Institute (ARDRI) at the University of Fort Hare. At this meeting, Professor Bekker was invited to undertake a socio-economic survey of the Amatola Basin. The Board of the Institute of Social and Economic Research at Rhodes University gave Professor Bekker permission in February 1981 to undertake the research project on condition that it was conducted in the fashion this Institute usually requires. It was subsequently agreed that the survey, known as 'Amatola Basin VII: Socio-economic survey', was to establish the basic demographic, kinship, consumption and employment patterns of the residents of the Amatola Basin. Practices and traditions related to dry land agriculture would also be identified , Digitised by Rhodes University Library on behalf of the Institute of Social and Economic Research (ISER)
- Full Text:
- Date Issued: 1981
- Authors: Bekker, S B , de Wet, Christopher J , Manona, Cecil W
- Date: 1981
- Subjects: Ciskei (South Africa) -- Rural conditions Agriculture -- South Africa -- Ciskei Middledrift (South Africa) Fingo (African people) Hlubi (African people) Agriculture -- South Africa -- Ciskei Amatola River Watershed (South Africa) -- Economic conditions Amatola River Watershed (South Africa) -- Social conditions
- Language: English
- Type: Book , Text
- Identifier: http://hdl.handle.net/10962/2282 , vital:20272 , ISBN 0868100730
- Description: Early in 1981, Professor S. Bekker of Rhodes University was invited to attend a meeting of the Amatola Basin Steering Committee of the Agricultural and Rural Development Research Institute (ARDRI) at the University of Fort Hare. At this meeting, Professor Bekker was invited to undertake a socio-economic survey of the Amatola Basin. The Board of the Institute of Social and Economic Research at Rhodes University gave Professor Bekker permission in February 1981 to undertake the research project on condition that it was conducted in the fashion this Institute usually requires. It was subsequently agreed that the survey, known as 'Amatola Basin VII: Socio-economic survey', was to establish the basic demographic, kinship, consumption and employment patterns of the residents of the Amatola Basin. Practices and traditions related to dry land agriculture would also be identified , Digitised by Rhodes University Library on behalf of the Institute of Social and Economic Research (ISER)
- Full Text:
- Date Issued: 1981
Predikant and priest : some Calvinist and Catholic role profiles of the religious functionary in South Africa : a comment and review of two empirical studies
- Authors: Higgins, Edward
- Date: 1972
- Subjects: Clergy -- South Africa , Clergy -- Office
- Language: English
- Type: Book , text
- Identifier: vital:551 , http://hdl.handle.net/10962/d1020578
- Description: A revised English version of "Les roles religieux dans le contexte multi-racial sud-africain : le profil du ministere dans le calvinisme et le catholicisme"
- Full Text:
- Date Issued: 1972
- Authors: Higgins, Edward
- Date: 1972
- Subjects: Clergy -- South Africa , Clergy -- Office
- Language: English
- Type: Book , text
- Identifier: vital:551 , http://hdl.handle.net/10962/d1020578
- Description: A revised English version of "Les roles religieux dans le contexte multi-racial sud-africain : le profil du ministere dans le calvinisme et le catholicisme"
- Full Text:
- Date Issued: 1972
A multi-threading software countermeasure to mitigate side channel analysis in the time domain
- Authors: Frieslaar, Ibraheem
- Date: 2019
- Subjects: Computer security , Data encryption (Computer science) , Noise generators (Electronics)
- Language: English
- Type: text , Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/71152 , vital:29790
- Description: This research is the first of its kind to investigate the utilisation of a multi-threading software-based countermeasure to mitigate Side Channel Analysis (SCA) attacks, with a particular focus on the AES-128 cryptographic algorithm. This investigation is novel, as there has not been a software-based countermeasure relying on multi-threading to our knowledge. The research has been tested on the Atmel microcontrollers, as well as a more fully featured system in the form of the popular Raspberry Pi that utilises the ARM7 processor. The main contributions of this research is the introduction of a multi-threading software based countermeasure used to mitigate SCA attacks on both an embedded device and a Raspberry Pi. These threads are comprised of various mathematical operations which are utilised to generate electromagnetic (EM) noise resulting in the obfuscation of the execution of the AES-128 algorithm. A novel EM noise generator known as the FRIES noise generator is implemented to obfuscate data captured in the EM field. FRIES comprises of hiding the execution of AES-128 algorithm within the EM noise generated by the 512 Secure Hash Algorithm (SHA) from the libcrypto++ and OpenSSL libraries. In order to evaluate the proposed countermeasure, a novel attack methodology was developed where the entire secret AES-128 encryption key was recovered from a Raspberry Pi, which has not been achieved before. The FRIES noise generator was pitted against this new attack vector and other known noise generators. The results exhibited that the FRIES noise generator withstood this attack whilst other existing techniques still leaked out secret information. The visual location of the AES-128 encryption algorithm in the EM spectrum and key recovery was prevented. These results demonstrated that the proposed multi-threading software based countermeasure was able to be resistant to existing and new forms of attacks, thus verifying that a multi-threading software based countermeasure can serve to mitigate SCA attacks.
- Full Text:
- Date Issued: 2019
- Authors: Frieslaar, Ibraheem
- Date: 2019
- Subjects: Computer security , Data encryption (Computer science) , Noise generators (Electronics)
- Language: English
- Type: text , Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/71152 , vital:29790
- Description: This research is the first of its kind to investigate the utilisation of a multi-threading software-based countermeasure to mitigate Side Channel Analysis (SCA) attacks, with a particular focus on the AES-128 cryptographic algorithm. This investigation is novel, as there has not been a software-based countermeasure relying on multi-threading to our knowledge. The research has been tested on the Atmel microcontrollers, as well as a more fully featured system in the form of the popular Raspberry Pi that utilises the ARM7 processor. The main contributions of this research is the introduction of a multi-threading software based countermeasure used to mitigate SCA attacks on both an embedded device and a Raspberry Pi. These threads are comprised of various mathematical operations which are utilised to generate electromagnetic (EM) noise resulting in the obfuscation of the execution of the AES-128 algorithm. A novel EM noise generator known as the FRIES noise generator is implemented to obfuscate data captured in the EM field. FRIES comprises of hiding the execution of AES-128 algorithm within the EM noise generated by the 512 Secure Hash Algorithm (SHA) from the libcrypto++ and OpenSSL libraries. In order to evaluate the proposed countermeasure, a novel attack methodology was developed where the entire secret AES-128 encryption key was recovered from a Raspberry Pi, which has not been achieved before. The FRIES noise generator was pitted against this new attack vector and other known noise generators. The results exhibited that the FRIES noise generator withstood this attack whilst other existing techniques still leaked out secret information. The visual location of the AES-128 encryption algorithm in the EM spectrum and key recovery was prevented. These results demonstrated that the proposed multi-threading software based countermeasure was able to be resistant to existing and new forms of attacks, thus verifying that a multi-threading software based countermeasure can serve to mitigate SCA attacks.
- Full Text:
- Date Issued: 2019
Code of Conduct for Australian companies with interests in the Republic of South Africa
- Date: Mar 1987
- Language: English
- Type: text
- Identifier: http://hdl.handle.net/10962/118204 , vital:34607
- Description: This is the first report under the voluntary Code of Conduct for Australian companies in South Africa. It marks Australia's entry into an area of monitoring and public reporting where the United States of America, the European Community (particularly the United Kingdom) and Canada have had Codes of Conduct since 1976 to 1978. Each of the countries concerned has companies with investment in South Africa and a physical presence there - through subsidiaries that operate as part of South African industry and that employ South African workers, including black workers. The Codes are intended to secure that companies from outside South Africa do not, when employing non-white (and particularly black) workers in South Africa, exploit the apartheid system. On the contrary, the objective is to work towards the elimination of discrimination at the industrial level - in pay rates, opportunities and otherwise - and at the same time to try to imp rove the position of the employees outside the work place. Those who press for stronger sanctions against South Africa and for active disinvestment policies criticise the Codes as weak palliatives for apartheid. In past years that might have been charged more forcibly. Today the existence of the Codes does not seem to be affecting decisions on sanctions. And the converse also seems to be true; with the sanctions that are presently operating the Codes continue to operate. Of course, when companies do disinvest, the Codes have fewer companies to cover and could eventually wither on that account. To the extent, therefore, that the Codes operate on the fact of foreign companies being in South Africa, they could be thought inconsistent with any policy of rapid disinvestment. However, there are at present no such policies operating at the level of Governments. A question arising from that is whether foreign companies, if they do remain in South Africa, should be subject to Codes and to reports back home as to their conduct, it being recognised that those reports, depending on their content and their reception, may either quieten or stir pressures for further disinvestment.
- Full Text:
- Date Issued: Mar 1987
- Date: Mar 1987
- Language: English
- Type: text
- Identifier: http://hdl.handle.net/10962/118204 , vital:34607
- Description: This is the first report under the voluntary Code of Conduct for Australian companies in South Africa. It marks Australia's entry into an area of monitoring and public reporting where the United States of America, the European Community (particularly the United Kingdom) and Canada have had Codes of Conduct since 1976 to 1978. Each of the countries concerned has companies with investment in South Africa and a physical presence there - through subsidiaries that operate as part of South African industry and that employ South African workers, including black workers. The Codes are intended to secure that companies from outside South Africa do not, when employing non-white (and particularly black) workers in South Africa, exploit the apartheid system. On the contrary, the objective is to work towards the elimination of discrimination at the industrial level - in pay rates, opportunities and otherwise - and at the same time to try to imp rove the position of the employees outside the work place. Those who press for stronger sanctions against South Africa and for active disinvestment policies criticise the Codes as weak palliatives for apartheid. In past years that might have been charged more forcibly. Today the existence of the Codes does not seem to be affecting decisions on sanctions. And the converse also seems to be true; with the sanctions that are presently operating the Codes continue to operate. Of course, when companies do disinvest, the Codes have fewer companies to cover and could eventually wither on that account. To the extent, therefore, that the Codes operate on the fact of foreign companies being in South Africa, they could be thought inconsistent with any policy of rapid disinvestment. However, there are at present no such policies operating at the level of Governments. A question arising from that is whether foreign companies, if they do remain in South Africa, should be subject to Codes and to reports back home as to their conduct, it being recognised that those reports, depending on their content and their reception, may either quieten or stir pressures for further disinvestment.
- Full Text:
- Date Issued: Mar 1987
Reliability analysis: assessment of hardware and human reliability
- Authors: Mafu, Masakheke
- Date: 2017
- Subjects: Bayesian statistical decision theory , Reliability (Engineering) , Human machine systems , Probabilities , Markov processes
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/6280 , vital:21077
- Description: Most reliability analyses involve the analysis of binary data. Practitioners in the field of reliability place great emphasis on analysing the time periods over which items or systems function (failure time analyses), which make use of different statistical models. This study intends to introduce, review and investigate four statistical models for modeling failure times of non-repairable items, and to utilise a Bayesian methodology to achieve this. The exponential, Rayleigh, gamma and Weibull distributions will be considered. The performance of the two non-informative priors will be investigated. An application of two failure time distributions will be carried out. To meet these objectives, the failure rate and the reliability functions of failure time distributions are calculated. Two non-informative priors, the Jeffreys prior and the general divergence prior, and the corresponding posteriors are derived for each distribution. Simulation studies for each distribution are carried out, where the coverage rates and credible intervals lengths are calculated and the results of these are discussed. The gamma distribution and the Weibull distribution are applied to failure time data.The Jeffreys prior is found to have better coverage rate than the general divergence prior. The general divergence shows undercoverage when used with the Rayleigh distribution. The Jeffreys prior produces coverage rates that are conservative when used with the exponential distribution. These priors give, on average, the same average interval lengths and increase as the value of the parameter increases. Both priors perform similar when used with the gamma distribution and the Weibull distribution. A thorough discussion and review of human reliability analysis (HRA) techniques will be considered. Twenty human reliability analysis (HRA) techniques are discussed; providing a background, description and advantages and disadvantages for each. Case studies in the nuclear industry, railway industry, and aviation industry are presented to show the importance and applications of HRA. Human error has been shown to be the major contributor to system failure.
- Full Text:
- Date Issued: 2017
- Authors: Mafu, Masakheke
- Date: 2017
- Subjects: Bayesian statistical decision theory , Reliability (Engineering) , Human machine systems , Probabilities , Markov processes
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/6280 , vital:21077
- Description: Most reliability analyses involve the analysis of binary data. Practitioners in the field of reliability place great emphasis on analysing the time periods over which items or systems function (failure time analyses), which make use of different statistical models. This study intends to introduce, review and investigate four statistical models for modeling failure times of non-repairable items, and to utilise a Bayesian methodology to achieve this. The exponential, Rayleigh, gamma and Weibull distributions will be considered. The performance of the two non-informative priors will be investigated. An application of two failure time distributions will be carried out. To meet these objectives, the failure rate and the reliability functions of failure time distributions are calculated. Two non-informative priors, the Jeffreys prior and the general divergence prior, and the corresponding posteriors are derived for each distribution. Simulation studies for each distribution are carried out, where the coverage rates and credible intervals lengths are calculated and the results of these are discussed. The gamma distribution and the Weibull distribution are applied to failure time data.The Jeffreys prior is found to have better coverage rate than the general divergence prior. The general divergence shows undercoverage when used with the Rayleigh distribution. The Jeffreys prior produces coverage rates that are conservative when used with the exponential distribution. These priors give, on average, the same average interval lengths and increase as the value of the parameter increases. Both priors perform similar when used with the gamma distribution and the Weibull distribution. A thorough discussion and review of human reliability analysis (HRA) techniques will be considered. Twenty human reliability analysis (HRA) techniques are discussed; providing a background, description and advantages and disadvantages for each. Case studies in the nuclear industry, railway industry, and aviation industry are presented to show the importance and applications of HRA. Human error has been shown to be the major contributor to system failure.
- Full Text:
- Date Issued: 2017
Expanding the SAR of Nontoxic Antiplasmodial Indolyl-3-ethanone Ethers and Thioethers.
- Lunga, Mayibongwe J, Chisango, Ruramai Lissa, Weyers, Carli, Isaacs, Michelle, Taylor, Dale, Edkins, Adrienne L, Khanye, Setshaba D, Hoppe, Heinrich C, Veale, Clinton G L
- Authors: Lunga, Mayibongwe J , Chisango, Ruramai Lissa , Weyers, Carli , Isaacs, Michelle , Taylor, Dale , Edkins, Adrienne L , Khanye, Setshaba D , Hoppe, Heinrich C , Veale, Clinton G L
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/122908 , vital:35370 , https://doi.org/10.1002/cmdc.201800235
- Description: Despite major strides in reducing Plasmodium falciparum infections, this parasite still accounts for roughly half a million annual deaths. This problem is compounded by the decreased efficacy of artemisinin combination therapies. Therefore, the development and optimisation of novel antimalarial chemotypes is critical. In this study, we describe our strategic approach to optimise a class of previously reported antimalarials, resulting in the discovery of 1‐(5‐chloro‐1H‐indol‐3‐yl)‐2‐[(4‐cyanophenyl)thio]ethanone (13) and 1‐(5‐chloro‐1H‐indol‐3‐yl)‐2‐[(4‐nitrophenyl)thio]ethanone (14), whose activity was equipotent to that of chloroquine against the P. falciparum 3D7 strain. Furthermore, these compounds were found to be nontoxic to HeLa cells as well as being non‐haemolytic to uninfected red blood cells. Intriguingly, several of our most promising compounds were found to be less active against the isogenic NF54 strain, highlighting possible issues with long‐term dependability of malarial strains. Finally compound 14 displayed similar activity against both the NF54 and K1 strains, suggesting that it inhibits a pathway that is uncompromised by K1 resistance.
- Full Text:
- Authors: Lunga, Mayibongwe J , Chisango, Ruramai Lissa , Weyers, Carli , Isaacs, Michelle , Taylor, Dale , Edkins, Adrienne L , Khanye, Setshaba D , Hoppe, Heinrich C , Veale, Clinton G L
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/122908 , vital:35370 , https://doi.org/10.1002/cmdc.201800235
- Description: Despite major strides in reducing Plasmodium falciparum infections, this parasite still accounts for roughly half a million annual deaths. This problem is compounded by the decreased efficacy of artemisinin combination therapies. Therefore, the development and optimisation of novel antimalarial chemotypes is critical. In this study, we describe our strategic approach to optimise a class of previously reported antimalarials, resulting in the discovery of 1‐(5‐chloro‐1H‐indol‐3‐yl)‐2‐[(4‐cyanophenyl)thio]ethanone (13) and 1‐(5‐chloro‐1H‐indol‐3‐yl)‐2‐[(4‐nitrophenyl)thio]ethanone (14), whose activity was equipotent to that of chloroquine against the P. falciparum 3D7 strain. Furthermore, these compounds were found to be nontoxic to HeLa cells as well as being non‐haemolytic to uninfected red blood cells. Intriguingly, several of our most promising compounds were found to be less active against the isogenic NF54 strain, highlighting possible issues with long‐term dependability of malarial strains. Finally compound 14 displayed similar activity against both the NF54 and K1 strains, suggesting that it inhibits a pathway that is uncompromised by K1 resistance.
- Full Text:
Solvent-free axial ligand substitution in octaphenoxyphthalocyaninato silicon complexes using microwave irradiation
- Maree, M David, Nyokong, Tebello
- Authors: Maree, M David , Nyokong, Tebello
- Date: 2001
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/304830 , vital:58494 , xlink:href="https://journals.sagepub.com/doi/epdf/10.3184/030823401103168974"
- Description: Several axially substituted octaphenoxy silicon phthalocyanines were prepared by condensation of the complexes used as axial ligands with octaphenoxyphthalocyaninato (dichloro) silicon under microwave irradiation.
- Full Text:
- Date Issued: 2001
- Authors: Maree, M David , Nyokong, Tebello
- Date: 2001
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/304830 , vital:58494 , xlink:href="https://journals.sagepub.com/doi/epdf/10.3184/030823401103168974"
- Description: Several axially substituted octaphenoxy silicon phthalocyanines were prepared by condensation of the complexes used as axial ligands with octaphenoxyphthalocyaninato (dichloro) silicon under microwave irradiation.
- Full Text:
- Date Issued: 2001
Novel camphor derivatives as potential asymmetric alkylation auxiliaries
- Authors: Skiti-Mama, Neliswa
- Date: 2008
- Subjects: Alkylation , Chemistry, Organic
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:10372 , http://hdl.handle.net/10948/1077 , Alkylation , Chemistry, Organic
- Description: The investigation has been focussed on the synthesis and characterisation of camphor-derived chiral auxiliaries that incorporate two camphor skeletons and an evaluation of their stereodirecting potential in ester α-benzylation reactions. Two regioisomeric camphorquinone-derived monoketals were synthesised and identified by 1D- and 2D-NMR, and X-ray crystallography. The stereo-directing potential of the alcohols that resulted from reduction of these ketones as chiral auxiliaries in the alkylation of carboxylate ester derivatives has been studied. The diastereoselectivities shown by NMR spectroscopy range from 14- 30 % d.e. for (1R,2 S, 3R) -2 ,2-[ (1R, 2 S, 3R) -bornane-2,3-dioxy] - bornan-3-ol and 68-74 % d.e. for (1R, 2S ,3R) -3 ,3-[ (1R, 2S ,3R) - bornane-2, 3 -dioxy]bornan-2-ol with selectivities that correlate with the size of the alkyl group in the ester moiety. Trapping of the enolates generated from (1R, 2S ,3R)-2, 2 -[(1R,2 S, 3R) -bornane- 2,3-dioxy]bornan-3-yl propanoate afforded both E- and Z-silyl ketene acetal derivatives in the ratio of 64:36 confirming the formation of both possible enolate structures during enolization. Chiral auxiliaries containing a hemiaminal ether blocking group as well as two chiral alcohols containing monothio-ketal blocking groups have also been synthesised. α-Benzylation of their corresponding propanoate esters afforded the alkylated product with disappointingly low diastereos electivities. Asymmetric reduction of α-keto esters attached to (1R, 2 S, 3R) - 2,2- [ (1R,2 S, 3R) -bornane-2, 3 -dioxy]bornan-3-ol and (1R, 2S ,3R) - 3,3- [ (1R,2 S, 3R) -bornane-2, 3 -dioxy]bornan-2-ol with metal hydrides proceeded with selectivities of up to 30 % d.e. Modelling of the keto ester derivatives at DFT levels provided useful insights into possible conformations adopted by the two α-keto esters and hence the preferred face of attack by metal hydride during reduction.
- Full Text:
- Date Issued: 2008
- Authors: Skiti-Mama, Neliswa
- Date: 2008
- Subjects: Alkylation , Chemistry, Organic
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:10372 , http://hdl.handle.net/10948/1077 , Alkylation , Chemistry, Organic
- Description: The investigation has been focussed on the synthesis and characterisation of camphor-derived chiral auxiliaries that incorporate two camphor skeletons and an evaluation of their stereodirecting potential in ester α-benzylation reactions. Two regioisomeric camphorquinone-derived monoketals were synthesised and identified by 1D- and 2D-NMR, and X-ray crystallography. The stereo-directing potential of the alcohols that resulted from reduction of these ketones as chiral auxiliaries in the alkylation of carboxylate ester derivatives has been studied. The diastereoselectivities shown by NMR spectroscopy range from 14- 30 % d.e. for (1R,2 S, 3R) -2 ,2-[ (1R, 2 S, 3R) -bornane-2,3-dioxy] - bornan-3-ol and 68-74 % d.e. for (1R, 2S ,3R) -3 ,3-[ (1R, 2S ,3R) - bornane-2, 3 -dioxy]bornan-2-ol with selectivities that correlate with the size of the alkyl group in the ester moiety. Trapping of the enolates generated from (1R, 2S ,3R)-2, 2 -[(1R,2 S, 3R) -bornane- 2,3-dioxy]bornan-3-yl propanoate afforded both E- and Z-silyl ketene acetal derivatives in the ratio of 64:36 confirming the formation of both possible enolate structures during enolization. Chiral auxiliaries containing a hemiaminal ether blocking group as well as two chiral alcohols containing monothio-ketal blocking groups have also been synthesised. α-Benzylation of their corresponding propanoate esters afforded the alkylated product with disappointingly low diastereos electivities. Asymmetric reduction of α-keto esters attached to (1R, 2 S, 3R) - 2,2- [ (1R,2 S, 3R) -bornane-2, 3 -dioxy]bornan-3-ol and (1R, 2S ,3R) - 3,3- [ (1R,2 S, 3R) -bornane-2, 3 -dioxy]bornan-2-ol with metal hydrides proceeded with selectivities of up to 30 % d.e. Modelling of the keto ester derivatives at DFT levels provided useful insights into possible conformations adopted by the two α-keto esters and hence the preferred face of attack by metal hydride during reduction.
- Full Text:
- Date Issued: 2008
Quinolone-isoniazid hybrids: Synthesis and preliminary in vitro cytotoxicity and anti-tuberculosis evaluation
- Beteck, Richard M, Seldon, Ronnett, Khanye, Setshaba D, Legoabe, Lesetja J, Hoppe, Heinrich C, Laming, Dustin, Jordaan, Audrey, Warner, Digby F
- Authors: Beteck, Richard M , Seldon, Ronnett , Khanye, Setshaba D , Legoabe, Lesetja J , Hoppe, Heinrich C , Laming, Dustin , Jordaan, Audrey , Warner, Digby F
- Date: 2019
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/123151 , vital:35410 , https://doi.org/10.1039/C8MD00480C
- Description: Herein, we propose novel quinolones incorporating an INH moiety as potential drug templates against TB. The quinolone-based compounds bearing an INH moiety attached via a hydrazide–hydrazone bond were synthesised and evaluated against Mycobacterium tuberculosis H37Rv (MTB). The compounds were also evaluated for cytotoxicity against HeLa cell lines. These compounds showed significant activity (MIC90) against MTB in the range of 0.2–8 μM without any cytotoxic effects. Compounds 10 (MIC90; 0.9 μM), 11 (MIC90; 0.2 μM), 12 (MIC90; 0.8 μM) and compound 15 (MIC90; 0.8 μM), the most active compounds in this series, demonstrate activities on par with INH and superior to those reported for the fluoroquinolones. The SAR analysis suggests that the nature of substituents at positions −1 and −3 of the quinolone nucleus influences anti-MTB activity. Aqueous solubility evaluation and in vitro metabolic stability of compound 12 highlights favourable drug-like properties for this compound class.
- Full Text:
- Date Issued: 2019
- Authors: Beteck, Richard M , Seldon, Ronnett , Khanye, Setshaba D , Legoabe, Lesetja J , Hoppe, Heinrich C , Laming, Dustin , Jordaan, Audrey , Warner, Digby F
- Date: 2019
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/123151 , vital:35410 , https://doi.org/10.1039/C8MD00480C
- Description: Herein, we propose novel quinolones incorporating an INH moiety as potential drug templates against TB. The quinolone-based compounds bearing an INH moiety attached via a hydrazide–hydrazone bond were synthesised and evaluated against Mycobacterium tuberculosis H37Rv (MTB). The compounds were also evaluated for cytotoxicity against HeLa cell lines. These compounds showed significant activity (MIC90) against MTB in the range of 0.2–8 μM without any cytotoxic effects. Compounds 10 (MIC90; 0.9 μM), 11 (MIC90; 0.2 μM), 12 (MIC90; 0.8 μM) and compound 15 (MIC90; 0.8 μM), the most active compounds in this series, demonstrate activities on par with INH and superior to those reported for the fluoroquinolones. The SAR analysis suggests that the nature of substituents at positions −1 and −3 of the quinolone nucleus influences anti-MTB activity. Aqueous solubility evaluation and in vitro metabolic stability of compound 12 highlights favourable drug-like properties for this compound class.
- Full Text:
- Date Issued: 2019
Leadership development within a learner representative council: a Namibian primary school case study
- Authors: Tjihuro, Jaqueline
- Date: 2018
- Subjects: School management and organization Namibia , Educational leadership Namibia , Student participation in administration Namibia , Student government Namibia
- Language: English
- Type: text , Thesis , Masters , MEd
- Identifier: http://hdl.handle.net/10962/61558 , vital:28036
- Description: Learners in Namibian primary schools are seemingly not brave enough to stand and raise their voice on issues that concern them. This is what Shekupakela-Nelulu (2008) wrote after a study she conducted on the Learners’ Representative Council (LRC) of a school in Namibia. She refers to a time when “the involvement of students in school affairs was seen by the regime as a political act and attempts by student leaders to involve themselves in educational issues were often quashed” (ibid., p. i). This situation will be all too familiar to South African readers, where a public holiday, Youth Day, was declared to mark the apartheid regime’s brutal treatment of learner protestors on June 16, 1976. While Namibia has not experienced events of such magnitude, the notion of learner voice is equally problematic and worthy of investigation. The absence of leadership development opportunities for learners has led to this research study which seeks to answer the central research question: How can learner leadership be developed in a LRC? I used an interpretive paradigm, adopting a qualitative approach in the study. Concurrently, the study was framed and guided by the second generation of Cultural Historical Activity Theory (CHAT) as an analytical tool to achieve my research goal. The following questions guided the study in two phases. Phase one: What were the perceived causes for the nonsustainability of the learner leadership (LL) club at the school? Phase two: How is the notion of learner leadership understood in the school? How is leadership developed on the LRC? What enables and constrains leadership development of learners on the LRC? The research participants were thirty LRC members from grades 6 and 7 and15 teachers who teach the LRC members. The principal and three HOD’s were also research participants being part of the Senior Management team. One of the HOD’s also fulfils the role of the guardian teacher to the LRC. A school board chairperson also participated in the Change Laboratory Workshop. Data was generated through multiple data sources such as questionnaires, individual interviews, a focus group interview and observation. The findings from phase one of the study revealed that the learner leadership club’s intervention was a success during the 2014 academic year, but the absence of the learner leadership club as an extra-mural activity affected the sustainability of the club into the next academic year 2015. Findings from phase two revealed that leadership opportunities did exist at the school for learner leadership development. However, a few challenges emerged relating to traditional views of leadership and constraining factors that could affect learner leadership development at the school. Thus, Change Laboratory workshops were held to find solutions to the challenges, in order to promote and enhance learner leadership development, hopefully for the future of the Namibian child.
- Full Text:
- Date Issued: 2018
Leadership development within a learner representative council: a Namibian primary school case study
- Authors: Tjihuro, Jaqueline
- Date: 2018
- Subjects: School management and organization Namibia , Educational leadership Namibia , Student participation in administration Namibia , Student government Namibia
- Language: English
- Type: text , Thesis , Masters , MEd
- Identifier: http://hdl.handle.net/10962/61558 , vital:28036
- Description: Learners in Namibian primary schools are seemingly not brave enough to stand and raise their voice on issues that concern them. This is what Shekupakela-Nelulu (2008) wrote after a study she conducted on the Learners’ Representative Council (LRC) of a school in Namibia. She refers to a time when “the involvement of students in school affairs was seen by the regime as a political act and attempts by student leaders to involve themselves in educational issues were often quashed” (ibid., p. i). This situation will be all too familiar to South African readers, where a public holiday, Youth Day, was declared to mark the apartheid regime’s brutal treatment of learner protestors on June 16, 1976. While Namibia has not experienced events of such magnitude, the notion of learner voice is equally problematic and worthy of investigation. The absence of leadership development opportunities for learners has led to this research study which seeks to answer the central research question: How can learner leadership be developed in a LRC? I used an interpretive paradigm, adopting a qualitative approach in the study. Concurrently, the study was framed and guided by the second generation of Cultural Historical Activity Theory (CHAT) as an analytical tool to achieve my research goal. The following questions guided the study in two phases. Phase one: What were the perceived causes for the nonsustainability of the learner leadership (LL) club at the school? Phase two: How is the notion of learner leadership understood in the school? How is leadership developed on the LRC? What enables and constrains leadership development of learners on the LRC? The research participants were thirty LRC members from grades 6 and 7 and15 teachers who teach the LRC members. The principal and three HOD’s were also research participants being part of the Senior Management team. One of the HOD’s also fulfils the role of the guardian teacher to the LRC. A school board chairperson also participated in the Change Laboratory Workshop. Data was generated through multiple data sources such as questionnaires, individual interviews, a focus group interview and observation. The findings from phase one of the study revealed that the learner leadership club’s intervention was a success during the 2014 academic year, but the absence of the learner leadership club as an extra-mural activity affected the sustainability of the club into the next academic year 2015. Findings from phase two revealed that leadership opportunities did exist at the school for learner leadership development. However, a few challenges emerged relating to traditional views of leadership and constraining factors that could affect learner leadership development at the school. Thus, Change Laboratory workshops were held to find solutions to the challenges, in order to promote and enhance learner leadership development, hopefully for the future of the Namibian child.
- Full Text:
- Date Issued: 2018
Orientation Course for New Lecturers Programme at Rhodes University, 1982
- Authors: Henderson, Derek Scott
- Date: 1982
- Language: English
- Type: text
- Identifier: vital:7568 , http://hdl.handle.net/10962/d1018445
- Full Text:
- Date Issued: 1982
- Authors: Henderson, Derek Scott
- Date: 1982
- Language: English
- Type: text
- Identifier: vital:7568 , http://hdl.handle.net/10962/d1018445
- Full Text:
- Date Issued: 1982
An exploration of leadership development in a learner representative structure in a secondary school, Oshana Region, Namibia
- Kadhepa-Kandjengo, Selma Ndeyapo
- Authors: Kadhepa-Kandjengo, Selma Ndeyapo
- Date: 2018
- Subjects: School management and organization -- Namibia , Educational leadership -- Namibia , Education, Secondary -- Namibia , Student government -- Namibia , Student participation in administration -- Namibia , Cultural Historical Activity Theory
- Language: English
- Type: text , Thesis , Masters , MEd
- Identifier: http://hdl.handle.net/10962/62450 , vital:28193
- Description: Before independence, Namibia inherited a system of Bantu education which was hierarchical, authoritarian and non-democratic. Upon independence, the educational sector went through numerous reforms which were meant to transform education and to make it more democratic, whereby all stakeholders can broadly participate. In spite of these reforms, leadership of schools has remained a hierarchical system, where a principal who, as an individual, runs the school without recognition of the potential leadership of others. Recent studies on leadership have called for shared leadership, whereby leadership is a practice, permeable to learner leaders and not associated with individuals. This research study aims to explore learner leadership development in the Learner Representative Council (LRC) structure at a secondary school in Namibia. The motivation of this research study was twofold - firstly, my personal interest in learner leadership was aroused by my teaching experience. The second reason was due to my realisation that the area was under-researched in Namibia, hence I wanted to fill the existing gap on learner leadership. The study critically engaged learners and teachers to help me get an understanding of learner leadership and the factors enabling learner leadership development. I also found that challenges which resulted in contradictions, hampered leadership development. The study took an interventionist approach and second generation Cultural Historical Activity Theory was used to surface tensions and contradictions affecting learner leadership development. Change Laboratory workshops enabled the expansive learning process with the 12 LRC members. Data was collected using semi-structured interviews, questionnaires, observation, document analysis and journaling. The study found that learner leadership was understood more in terms of traditional views of leadership, whereby a learner needed to possess certain qualities in order to lead. The findings further pointed out that the LRC members were mainly involved in managerial roles and not really leadership roles, as such, and they were not involved in decision-making at the school. Although provision for the LRC body is made in an Educational Act, historical and cultural forces account for teachers’ reluctance to support the LRC members, as well as for silence of learner voice. I hope that findings from this research study strengthen learner leadership structures in schools and contribute to the creation of knowledge on learner leadership in Namibia.
- Full Text:
- Date Issued: 2018
- Authors: Kadhepa-Kandjengo, Selma Ndeyapo
- Date: 2018
- Subjects: School management and organization -- Namibia , Educational leadership -- Namibia , Education, Secondary -- Namibia , Student government -- Namibia , Student participation in administration -- Namibia , Cultural Historical Activity Theory
- Language: English
- Type: text , Thesis , Masters , MEd
- Identifier: http://hdl.handle.net/10962/62450 , vital:28193
- Description: Before independence, Namibia inherited a system of Bantu education which was hierarchical, authoritarian and non-democratic. Upon independence, the educational sector went through numerous reforms which were meant to transform education and to make it more democratic, whereby all stakeholders can broadly participate. In spite of these reforms, leadership of schools has remained a hierarchical system, where a principal who, as an individual, runs the school without recognition of the potential leadership of others. Recent studies on leadership have called for shared leadership, whereby leadership is a practice, permeable to learner leaders and not associated with individuals. This research study aims to explore learner leadership development in the Learner Representative Council (LRC) structure at a secondary school in Namibia. The motivation of this research study was twofold - firstly, my personal interest in learner leadership was aroused by my teaching experience. The second reason was due to my realisation that the area was under-researched in Namibia, hence I wanted to fill the existing gap on learner leadership. The study critically engaged learners and teachers to help me get an understanding of learner leadership and the factors enabling learner leadership development. I also found that challenges which resulted in contradictions, hampered leadership development. The study took an interventionist approach and second generation Cultural Historical Activity Theory was used to surface tensions and contradictions affecting learner leadership development. Change Laboratory workshops enabled the expansive learning process with the 12 LRC members. Data was collected using semi-structured interviews, questionnaires, observation, document analysis and journaling. The study found that learner leadership was understood more in terms of traditional views of leadership, whereby a learner needed to possess certain qualities in order to lead. The findings further pointed out that the LRC members were mainly involved in managerial roles and not really leadership roles, as such, and they were not involved in decision-making at the school. Although provision for the LRC body is made in an Educational Act, historical and cultural forces account for teachers’ reluctance to support the LRC members, as well as for silence of learner voice. I hope that findings from this research study strengthen learner leadership structures in schools and contribute to the creation of knowledge on learner leadership in Namibia.
- Full Text:
- Date Issued: 2018
An evaluation of the process and impact of outsourcing information technology (IT) services by Eastern Cape Treasury Department (ECTD) to the State Information Technology Agency (SITA)
- Authors: Mdlokovi, Lulama Reuben
- Date: 2008
- Subjects: State Information Technology Agency (South Africa) Administrative agencies -- South Africa Information technology -- Management Technology -- Information services Information services industry Telecommunication Value-added networks (Computer networks)
- Language: English
- Type: Thesis , Masters , MBA
- Identifier: vital:743 , http://hdl.handle.net/10962/d1003864
- Description: The aim of this research is to evaluate the process and impact of outsourcing information technology (IT) services of Eastern Cape Treasury Department (ECTD) to State Information Technology Agency (SITA). This research study has been prompted by the fact that the South African Government through the National Department of Public Service and Administration has established SITA with a sole purpose of improving service delivery by all national, provincial and local government departments. The researcher’s concern is whether the relationship between SITA and these departments is working or not. The research paradigm adopted is a constructivist approach and the ontological position adopted assumed multiple realities. The research method used in this study is the evaluation research method. Key to the research procedure was the fact that four senior officials were interviewed using audio recording, where in two were each chosen from SITA and ECTD. The researcher used document analysis and interviews as a means of collecting data. Separate open-ended questions for SITA and ECTD were structured in such a way that it would be easy to extract themes describing the details of a particular question. The researcher made use of thematic analysis. The theory drive-code development process was key in the research analysis. ECTD outsourced to SITA the following IT services, namely, provision or maintenance of a private telecommunication network (PTN) or a value-added network (VAN); transversal information systems and its data-processing or associated services; training in IT/IS; application software development; maintenance services for IT software or infrastructure; data-processing or associated services for specific IT applications or systems such as website development; and IT support. The interviewed officials from ECTD contend that they used the SCM Guide and SITA ACT when pursuing IT outsourcing for projects such as those listed above. One of the key projects outsourced to SITA is the IFMS, which is a project programme of the National Treasury Department working closely with provinces (e.g. ECTD), National Department of Public Service and Administration (NDPSA) and SITA. The IFMS project has been implemented following the SCM guidelines. The key SCM Guide components are demand, acquisition, logistics, and disposal management. The engagement model used by SITA to guide them on the process of engaging in an IT outsourcing relationship has, according to the officials interviewed, been a success. SITA uses a standard contract wherein other specific contracts receive minor adjustments. The impact of IT outsourcing has shown increases in customer satisfaction improvement, transformation of government procurement and provisioning practices, appointment of Consultants, interpretation of the Preferential Procurement Policy, promotion of the consistent application of Best Practices, information systems security environment, and improving service delivery.
- Full Text:
- Date Issued: 2008
- Authors: Mdlokovi, Lulama Reuben
- Date: 2008
- Subjects: State Information Technology Agency (South Africa) Administrative agencies -- South Africa Information technology -- Management Technology -- Information services Information services industry Telecommunication Value-added networks (Computer networks)
- Language: English
- Type: Thesis , Masters , MBA
- Identifier: vital:743 , http://hdl.handle.net/10962/d1003864
- Description: The aim of this research is to evaluate the process and impact of outsourcing information technology (IT) services of Eastern Cape Treasury Department (ECTD) to State Information Technology Agency (SITA). This research study has been prompted by the fact that the South African Government through the National Department of Public Service and Administration has established SITA with a sole purpose of improving service delivery by all national, provincial and local government departments. The researcher’s concern is whether the relationship between SITA and these departments is working or not. The research paradigm adopted is a constructivist approach and the ontological position adopted assumed multiple realities. The research method used in this study is the evaluation research method. Key to the research procedure was the fact that four senior officials were interviewed using audio recording, where in two were each chosen from SITA and ECTD. The researcher used document analysis and interviews as a means of collecting data. Separate open-ended questions for SITA and ECTD were structured in such a way that it would be easy to extract themes describing the details of a particular question. The researcher made use of thematic analysis. The theory drive-code development process was key in the research analysis. ECTD outsourced to SITA the following IT services, namely, provision or maintenance of a private telecommunication network (PTN) or a value-added network (VAN); transversal information systems and its data-processing or associated services; training in IT/IS; application software development; maintenance services for IT software or infrastructure; data-processing or associated services for specific IT applications or systems such as website development; and IT support. The interviewed officials from ECTD contend that they used the SCM Guide and SITA ACT when pursuing IT outsourcing for projects such as those listed above. One of the key projects outsourced to SITA is the IFMS, which is a project programme of the National Treasury Department working closely with provinces (e.g. ECTD), National Department of Public Service and Administration (NDPSA) and SITA. The IFMS project has been implemented following the SCM guidelines. The key SCM Guide components are demand, acquisition, logistics, and disposal management. The engagement model used by SITA to guide them on the process of engaging in an IT outsourcing relationship has, according to the officials interviewed, been a success. SITA uses a standard contract wherein other specific contracts receive minor adjustments. The impact of IT outsourcing has shown increases in customer satisfaction improvement, transformation of government procurement and provisioning practices, appointment of Consultants, interpretation of the Preferential Procurement Policy, promotion of the consistent application of Best Practices, information systems security environment, and improving service delivery.
- Full Text:
- Date Issued: 2008
BODIPY dyes for singlet oxygen and optical limiting applications
- Authors: Harris, Jessica
- Date: 2018
- Subjects: Photosensitizing compounds , Active oxygen -- Physiological effect , Photochemotherapy , Cancer -- Treatment , Nonlinear optics , BODIPY (Boron-dipyrromethene)
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/58002 , vital:27014
- Description: A series of structurally related BODIPY dyes were synthesised and characterised. Their photophysical properties were studied in order to determine whether they would be suitable candidates for use as photosensitisers in the photodynamic therapy (PDT) treatment of cancer. The synthesis of two highly fluorescent BODIPY cores was achieved via the acid-catalysed condensation of a pyrrole and a functionalised aldehyde. In order to promote intersystem crossing, and hence improve the singlet oxygen generation of these dyes, bromine atoms were added at the 2,6-positions of the BODIPY core. These dibrominated analogues showed good singlet oxygen quantum yields, and excellent photostability in ethanol. In order to red-shift the main spectral bands of the BODIPY dyes towards the therapeutic window, vinyl/ styryl groups were introduced at the 3-, 5-, and 7-positions via a modified Knoevengal condensation reaction. The addition of vinyl/ styryl groups to the BODIPY core caused an increase in fluorescence quantum yield as well as a decrease in singlet oxygen quantum yield with respect to the dibrominated analogues. However, two of the red-shifted BODIPY dyes still showed moderate singlet oxygen quantum yields. The use of BODIPY dyes in nonlinear optics (NLO) was explored. The nonlinear optical characterisations and optical limiting properties of a series of 3,5-dithienylenevinylene BODIPY dyes were studied, both in dimethylformamide (DMF) solution and when embedded in poly(bisphenol A carbonate) (PBC) as thin films. The 3,5-dithienylenevinylene BODIPY dyes showed typical nonlinear absorption behaviour, with reverse saturable absorption (RSA) profiles, indicating that they have potential as optical limiters. The second-order hyperpolarizability (Y), and third-order nonlinear susceptibility (/m[/(3)]) values are also reported for these dyes. The optical limiting values of one of the BODIPY dyes in solution, and two of the BODIPY-embedded PBC films, were below the maximum threshold of 0.95 J-cm-2. The effect of addition of substituents on the electronic structure of the BODIPY dyes was investigated using TD-DFT calculations. The calculated trends closely followed those determined experimentally.
- Full Text:
- Date Issued: 2018
- Authors: Harris, Jessica
- Date: 2018
- Subjects: Photosensitizing compounds , Active oxygen -- Physiological effect , Photochemotherapy , Cancer -- Treatment , Nonlinear optics , BODIPY (Boron-dipyrromethene)
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/58002 , vital:27014
- Description: A series of structurally related BODIPY dyes were synthesised and characterised. Their photophysical properties were studied in order to determine whether they would be suitable candidates for use as photosensitisers in the photodynamic therapy (PDT) treatment of cancer. The synthesis of two highly fluorescent BODIPY cores was achieved via the acid-catalysed condensation of a pyrrole and a functionalised aldehyde. In order to promote intersystem crossing, and hence improve the singlet oxygen generation of these dyes, bromine atoms were added at the 2,6-positions of the BODIPY core. These dibrominated analogues showed good singlet oxygen quantum yields, and excellent photostability in ethanol. In order to red-shift the main spectral bands of the BODIPY dyes towards the therapeutic window, vinyl/ styryl groups were introduced at the 3-, 5-, and 7-positions via a modified Knoevengal condensation reaction. The addition of vinyl/ styryl groups to the BODIPY core caused an increase in fluorescence quantum yield as well as a decrease in singlet oxygen quantum yield with respect to the dibrominated analogues. However, two of the red-shifted BODIPY dyes still showed moderate singlet oxygen quantum yields. The use of BODIPY dyes in nonlinear optics (NLO) was explored. The nonlinear optical characterisations and optical limiting properties of a series of 3,5-dithienylenevinylene BODIPY dyes were studied, both in dimethylformamide (DMF) solution and when embedded in poly(bisphenol A carbonate) (PBC) as thin films. The 3,5-dithienylenevinylene BODIPY dyes showed typical nonlinear absorption behaviour, with reverse saturable absorption (RSA) profiles, indicating that they have potential as optical limiters. The second-order hyperpolarizability (Y), and third-order nonlinear susceptibility (/m[/(3)]) values are also reported for these dyes. The optical limiting values of one of the BODIPY dyes in solution, and two of the BODIPY-embedded PBC films, were below the maximum threshold of 0.95 J-cm-2. The effect of addition of substituents on the electronic structure of the BODIPY dyes was investigated using TD-DFT calculations. The calculated trends closely followed those determined experimentally.
- Full Text:
- Date Issued: 2018
Synthesis and in vitro biological evaluation of 2,3-substituted quinoline derivatives
- Bokosi, Fostino Raphael Bentry
- Authors: Bokosi, Fostino Raphael Bentry
- Date: 2020
- Subjects: Quinoline , Malaria Chemotherapy , Tuberculosis Chemotherapy , African trypanosomiasis Chemotherapy
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/163193 , vital:41017
- Description: The urgent need for new systemic pharmacological entities prompted us to report a library of 2,3-substituted quinoline derivatives. Considering the ubiquity of quinoline-containing compounds in pharmacologically active small molecules, synthesized 2,3-substituted quinoline derivatives were in vitro biologically evaluated for their potential antitubercular, antimalarial and antitrypanosomal activities. Quinoline scaffold was achieved by the Vilsmeier-Haack methodology, affording synthetically useful chloro and formyl substituents on C-2 and C-3 respectively. These two substituents acted as handles in expanding the chemical space around the quinoline ring. Target compounds were synthesized in six to seven steps, employing conventional synthetic organic protocols adapted from various literature. The final compounds were accessed in moderate to good yields. The structural identity of each compound was confirmed by common spectroscopic techniques. Aryl quinoline carboxamide derivatives 3.113 – 3.126 were isolated as rotamers, hence, Variable-Temperature Nuclear Magnetic Resonance (VT-NMR) was employed in resolving 1H splitting. At elevated temperature (~328 K); N-methylene carbons were not visible on 13C NMR due to signal line broadening effects. The presence of these nuclei in such cases was, however, supported by 2-dimensional NMR and high-resolution MS data. Most of the compounds achieved in this study displayed promising antimalarial activity against chloroquine-sensitive 3D7 strain of Plasmodium falciparum compared to antitrypanosomal activity against Trypanosoma brucei brucei 427 strain. In particular, compounds 3.80 and 3.108 showed superior activity against chloroquine-sensitive 3D7 P. falciparum strain with IC50 values < 1 μM. More importantly, most of the compounds were non-toxic as determined by HeLa cells, indicating their selectivity towards the parasites. Exploring the space provided on the quinoline scaffold revealed that methoxy incorporation on C-2 is very critical in enhancing antimalarial activity of this class of quinoline compounds. The preliminary SAR of compounds 3.57 – 3.72 showed that compounds containing the 3-cinnamate exhibited enhanced antimalarial activity compared to 2 and 4-cinnamates. Finally, benzamide compounds 3.113 − 3.126 showed poor activity against Mycobacterium tuberculosis H37Rv strain with only compounds 3.113, 3.117 – 3.120 and 3.126 showing appreciable MIC90 values in the range of 40 – 85 μM. , Thesis (MSc) -- Faculty of Science, Chemistry, 2020
- Full Text:
- Date Issued: 2020
- Authors: Bokosi, Fostino Raphael Bentry
- Date: 2020
- Subjects: Quinoline , Malaria Chemotherapy , Tuberculosis Chemotherapy , African trypanosomiasis Chemotherapy
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/163193 , vital:41017
- Description: The urgent need for new systemic pharmacological entities prompted us to report a library of 2,3-substituted quinoline derivatives. Considering the ubiquity of quinoline-containing compounds in pharmacologically active small molecules, synthesized 2,3-substituted quinoline derivatives were in vitro biologically evaluated for their potential antitubercular, antimalarial and antitrypanosomal activities. Quinoline scaffold was achieved by the Vilsmeier-Haack methodology, affording synthetically useful chloro and formyl substituents on C-2 and C-3 respectively. These two substituents acted as handles in expanding the chemical space around the quinoline ring. Target compounds were synthesized in six to seven steps, employing conventional synthetic organic protocols adapted from various literature. The final compounds were accessed in moderate to good yields. The structural identity of each compound was confirmed by common spectroscopic techniques. Aryl quinoline carboxamide derivatives 3.113 – 3.126 were isolated as rotamers, hence, Variable-Temperature Nuclear Magnetic Resonance (VT-NMR) was employed in resolving 1H splitting. At elevated temperature (~328 K); N-methylene carbons were not visible on 13C NMR due to signal line broadening effects. The presence of these nuclei in such cases was, however, supported by 2-dimensional NMR and high-resolution MS data. Most of the compounds achieved in this study displayed promising antimalarial activity against chloroquine-sensitive 3D7 strain of Plasmodium falciparum compared to antitrypanosomal activity against Trypanosoma brucei brucei 427 strain. In particular, compounds 3.80 and 3.108 showed superior activity against chloroquine-sensitive 3D7 P. falciparum strain with IC50 values < 1 μM. More importantly, most of the compounds were non-toxic as determined by HeLa cells, indicating their selectivity towards the parasites. Exploring the space provided on the quinoline scaffold revealed that methoxy incorporation on C-2 is very critical in enhancing antimalarial activity of this class of quinoline compounds. The preliminary SAR of compounds 3.57 – 3.72 showed that compounds containing the 3-cinnamate exhibited enhanced antimalarial activity compared to 2 and 4-cinnamates. Finally, benzamide compounds 3.113 − 3.126 showed poor activity against Mycobacterium tuberculosis H37Rv strain with only compounds 3.113, 3.117 – 3.120 and 3.126 showing appreciable MIC90 values in the range of 40 – 85 μM. , Thesis (MSc) -- Faculty of Science, Chemistry, 2020
- Full Text:
- Date Issued: 2020
A reconciliation study of different resource estimation methods and drill hole spacing as applied to the Langer Heinrich calcrete-hosted uranium deposit, Namibia
- Authors: Baufeldt, Sven
- Date: 2018
- Subjects: Uranium -- Namibia , Calcretes -- Namibia , Carnotite -- Namibia , Uranium mines and mining -- Namibia , Uranium ores -- Geology -- Namibia , Langer-Heinrich Uranium mine
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/62527 , vital:28203
- Description: The Langer Heinrich calcrete hosted uranium deposit is situated approximately 90 km to east of the coastal town of Swakopmund in Namibia. It is run by an Australian owned company, Paladin Energy Limited, along with China National Nuclear Corporation (CNNC) who maintain 25% of the shares. Production commenced in 2007 and has been ongoing. Carnotite is the primary and only ore mineral, and the nature of mineralisation within the Langer Heinrich palaeo channel dictates westward-directed continuous open pit mining. Smaller-scale 1micro pits target near-surface, high-grade, lenses toward the east. The high variability in uranium grade over relatively short distances complicates the grade estimation process. This combined with a low uranium price, and a study aimed at optimising of mine production is one of the key drivers for the research presented in this thesis. The efficacy of four resource estimation techniques, commonly used in the mining industry, are investigated by application to variable exploration, infill drilling and grade-control drill pattern spacing. The drill spacing includes regular grids of 50 m x 50 m, 25 m x 25 m and 12,5 m x 12,5 m exploration data. Also included is grade control drill data, drilled on a 4 m x 4 m spacing. The current selective mining unit (SMU) is 4mE x 4mN x 3mRl which is an indication of the minimum dimension whereby the loading equipment can separate ore from waste. The two datasets are processed by four estimation techniques: Inverse Distance Weighting (IDW, squared and cubed), Ordinary Kriging (OK), Multiple Indicator Kriging (MIK) and Conditional Simulation (CS). The two datasets consisted of real-time mining data from pit G1 (micro-pit) in the eastern parts of the mining licence, and pit H1 (continuous larger open pit) in the western area of the palaeo channel. The reconciliation project aims to provide results suitable for devising optimised mining strategies, particularly in future targets where drill spacing can perhaps be improved to provide suitable data with a greater cost saving strategy. Along with the optimal drill spacing or combination thereof, a preferred estimation technique can be suggested and recommended for future operations that involve mining of surficial calcrete-hosted uranium deposits. Results of this study show that 12,5 m x 12,5 m drill spacing provided estimation accuracies similar to that of the narrow 4 m x 4 m grade control spacing (blast hole drilling spacing). The 12,5 m x 12,5m spacing has potential for accurate grade estimations during mining, and could be supplemented by infill downhole radiometric logging on a 4 m x 4 m spacing when 1 Micro pit: Small pits within palaeo channel usually targeted for their near surface high-grade ore necessary. In general, Multiple Indicator Kriging (MIK) provided the most accurate and robust estimations on the wider spaced exploration data and conditional simulation (CS) proved more efficient on the narrow grade control data. These results correspond with current exploration practices for surficial uranium deposits world-wide. Deposit type, therefore complexity and hence SMU sizes play a pivotal role in drill hole planning and estimation accuracies.
- Full Text:
- Date Issued: 2018
- Authors: Baufeldt, Sven
- Date: 2018
- Subjects: Uranium -- Namibia , Calcretes -- Namibia , Carnotite -- Namibia , Uranium mines and mining -- Namibia , Uranium ores -- Geology -- Namibia , Langer-Heinrich Uranium mine
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/62527 , vital:28203
- Description: The Langer Heinrich calcrete hosted uranium deposit is situated approximately 90 km to east of the coastal town of Swakopmund in Namibia. It is run by an Australian owned company, Paladin Energy Limited, along with China National Nuclear Corporation (CNNC) who maintain 25% of the shares. Production commenced in 2007 and has been ongoing. Carnotite is the primary and only ore mineral, and the nature of mineralisation within the Langer Heinrich palaeo channel dictates westward-directed continuous open pit mining. Smaller-scale 1micro pits target near-surface, high-grade, lenses toward the east. The high variability in uranium grade over relatively short distances complicates the grade estimation process. This combined with a low uranium price, and a study aimed at optimising of mine production is one of the key drivers for the research presented in this thesis. The efficacy of four resource estimation techniques, commonly used in the mining industry, are investigated by application to variable exploration, infill drilling and grade-control drill pattern spacing. The drill spacing includes regular grids of 50 m x 50 m, 25 m x 25 m and 12,5 m x 12,5 m exploration data. Also included is grade control drill data, drilled on a 4 m x 4 m spacing. The current selective mining unit (SMU) is 4mE x 4mN x 3mRl which is an indication of the minimum dimension whereby the loading equipment can separate ore from waste. The two datasets are processed by four estimation techniques: Inverse Distance Weighting (IDW, squared and cubed), Ordinary Kriging (OK), Multiple Indicator Kriging (MIK) and Conditional Simulation (CS). The two datasets consisted of real-time mining data from pit G1 (micro-pit) in the eastern parts of the mining licence, and pit H1 (continuous larger open pit) in the western area of the palaeo channel. The reconciliation project aims to provide results suitable for devising optimised mining strategies, particularly in future targets where drill spacing can perhaps be improved to provide suitable data with a greater cost saving strategy. Along with the optimal drill spacing or combination thereof, a preferred estimation technique can be suggested and recommended for future operations that involve mining of surficial calcrete-hosted uranium deposits. Results of this study show that 12,5 m x 12,5 m drill spacing provided estimation accuracies similar to that of the narrow 4 m x 4 m grade control spacing (blast hole drilling spacing). The 12,5 m x 12,5m spacing has potential for accurate grade estimations during mining, and could be supplemented by infill downhole radiometric logging on a 4 m x 4 m spacing when 1 Micro pit: Small pits within palaeo channel usually targeted for their near surface high-grade ore necessary. In general, Multiple Indicator Kriging (MIK) provided the most accurate and robust estimations on the wider spaced exploration data and conditional simulation (CS) proved more efficient on the narrow grade control data. These results correspond with current exploration practices for surficial uranium deposits world-wide. Deposit type, therefore complexity and hence SMU sizes play a pivotal role in drill hole planning and estimation accuracies.
- Full Text:
- Date Issued: 2018
Development and assessment of gastric-retentive sustained release metronidazole microcapsules
- Authors: Makan, Anjana
- Date: 2017
- Subjects: Metronidazole , Drug delivery systems , Helicobacter pylori , High performance liquid chromatography , Gas chromatography , Drugs , Drugs Controlled release
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/59240 , vital:27491
- Description: Helicobacter pylori is one of the most common pathogenic bacterial infections and is the leading cause of gastritis, gastroduodenal ulcer disease and gastric cancers. Studies have revealed the prevalence of Helicobacter pylori is high in many countries around the globe. Although Helicobacter pylori is highly sensitive to antimicrobial agents in vitro the clinical eradication rate of the disease is still low. The instability of API at gastric pH, low concentration of API in the gastric mucosa and short gastric residence times are the main reasons for poor eradication rates. The high prevalence rate of this disease necessitates the design and development of gastric-retentive site specific oral dosage forms for the optimized delivery of existing therapeutic molecules and may be an approach to improving the eradication rate of Helicobacter pylori. Metronidazole (MTZ) is a 5-nitroimidazole derivative that exhibits antibiotic and antiprotozoal activity. MTZ is used in combination with other compounds for the treatment of Helicobacter pylori in peptic ulcer disease. MTZ is a potential candidate for inclusion in a sustained release gastric-retentive delivery system that acts in the stomach and since it is unstable in the intestinal/colonic environment enhancing gastric residence time would be a therapeutic advantage. MTZ is a cost-effective therapy that exhibits good anti-microbial activity and has a favourable pharmacokinetic profile. A sustained release gastric-retentive formulation is therefore proposed as an approach to enhance the local delivery of MTZ and improve treatment outcomes for patients infected with Helicobacter pylori. A stability indicating Reversed-Phase High Performance Liquid Chromatography (RP- HPLC) method for the quantitation of MTZ in pharmaceutical dosage forms was developed and optimised using a Central Composite Design (CCD) approach. The RP-HPLC method was found to be linear, accurate, precise, sensitive, selective, and was applied to the analysis of MTZ in commercially available medicines. Preformulation studies were conducted as preparative work prior to manufacture gastric- retentive sustained release MTZ microcapsules. The experiments conducted were tailored for the development of sustained release MTZ microcapsules using a solvent evaporation method. The particle size and shape of the microcapsules was investigated using Scanning Electron Microscopy (SEM). MTZ- excipient compatibility studies were performed using Fourier Transform Infra-red Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC) and X-Ray Diffraction (XRD). The results revealed that no definite interaction between MTZ and intended excipients to be used for manufacture of MTZ formulations occurred. A solvent evaporation procedure was used for the manufacture of MTZ microcapsules. Preliminary formulations were manufactured using two different grades of Methocel® at various levels. In addition the impact of processing parameters on performance was also investigated. The formulations were assessed in terms of in vitro release, buoyancy, yield, encapsulation efficiency and microcapsule size. Formulation optimisation was undertaken using a CCD approach and numerical optimisation was used to predict an optimised formulation composition that would produce minimal initial MTZ release, maximum MTZ release at 12 hours and maximum buoyancy, encapsulation efficiency and yield. The kinetics of MTZ release from microcapsules was established by fitting in vitro release data to different mathematical models. Higuchi model and first-order model appeared to best fit the data as majority of the formulation batches had highest R2 values for these models. Short-term stability assessment of the optimised formulation was established by undertaking stability studies at 25°C/60% RH and 40°C/75%RH. No significant changes in any of the CQA were observed over 30 days of stability testing. A gas chromatographic (GC) method was developed and validated for the quantitation of residual acetone and n-hexane. The optimised formulation contained 213.60 ppm/g acetone and 25.23 ppm/g n-hexane which are well below the limits set for residual solvents. In conclusion, gastric-retentive sustained release MTZ microcapsules with potential for further development and optimisation have been successfully developed and assessed in these studies. , Thesis (MSc) -- Faculty of Pharmacy, Pharmacy, 2017
- Full Text:
- Date Issued: 2017
- Authors: Makan, Anjana
- Date: 2017
- Subjects: Metronidazole , Drug delivery systems , Helicobacter pylori , High performance liquid chromatography , Gas chromatography , Drugs , Drugs Controlled release
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/59240 , vital:27491
- Description: Helicobacter pylori is one of the most common pathogenic bacterial infections and is the leading cause of gastritis, gastroduodenal ulcer disease and gastric cancers. Studies have revealed the prevalence of Helicobacter pylori is high in many countries around the globe. Although Helicobacter pylori is highly sensitive to antimicrobial agents in vitro the clinical eradication rate of the disease is still low. The instability of API at gastric pH, low concentration of API in the gastric mucosa and short gastric residence times are the main reasons for poor eradication rates. The high prevalence rate of this disease necessitates the design and development of gastric-retentive site specific oral dosage forms for the optimized delivery of existing therapeutic molecules and may be an approach to improving the eradication rate of Helicobacter pylori. Metronidazole (MTZ) is a 5-nitroimidazole derivative that exhibits antibiotic and antiprotozoal activity. MTZ is used in combination with other compounds for the treatment of Helicobacter pylori in peptic ulcer disease. MTZ is a potential candidate for inclusion in a sustained release gastric-retentive delivery system that acts in the stomach and since it is unstable in the intestinal/colonic environment enhancing gastric residence time would be a therapeutic advantage. MTZ is a cost-effective therapy that exhibits good anti-microbial activity and has a favourable pharmacokinetic profile. A sustained release gastric-retentive formulation is therefore proposed as an approach to enhance the local delivery of MTZ and improve treatment outcomes for patients infected with Helicobacter pylori. A stability indicating Reversed-Phase High Performance Liquid Chromatography (RP- HPLC) method for the quantitation of MTZ in pharmaceutical dosage forms was developed and optimised using a Central Composite Design (CCD) approach. The RP-HPLC method was found to be linear, accurate, precise, sensitive, selective, and was applied to the analysis of MTZ in commercially available medicines. Preformulation studies were conducted as preparative work prior to manufacture gastric- retentive sustained release MTZ microcapsules. The experiments conducted were tailored for the development of sustained release MTZ microcapsules using a solvent evaporation method. The particle size and shape of the microcapsules was investigated using Scanning Electron Microscopy (SEM). MTZ- excipient compatibility studies were performed using Fourier Transform Infra-red Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC) and X-Ray Diffraction (XRD). The results revealed that no definite interaction between MTZ and intended excipients to be used for manufacture of MTZ formulations occurred. A solvent evaporation procedure was used for the manufacture of MTZ microcapsules. Preliminary formulations were manufactured using two different grades of Methocel® at various levels. In addition the impact of processing parameters on performance was also investigated. The formulations were assessed in terms of in vitro release, buoyancy, yield, encapsulation efficiency and microcapsule size. Formulation optimisation was undertaken using a CCD approach and numerical optimisation was used to predict an optimised formulation composition that would produce minimal initial MTZ release, maximum MTZ release at 12 hours and maximum buoyancy, encapsulation efficiency and yield. The kinetics of MTZ release from microcapsules was established by fitting in vitro release data to different mathematical models. Higuchi model and first-order model appeared to best fit the data as majority of the formulation batches had highest R2 values for these models. Short-term stability assessment of the optimised formulation was established by undertaking stability studies at 25°C/60% RH and 40°C/75%RH. No significant changes in any of the CQA were observed over 30 days of stability testing. A gas chromatographic (GC) method was developed and validated for the quantitation of residual acetone and n-hexane. The optimised formulation contained 213.60 ppm/g acetone and 25.23 ppm/g n-hexane which are well below the limits set for residual solvents. In conclusion, gastric-retentive sustained release MTZ microcapsules with potential for further development and optimisation have been successfully developed and assessed in these studies. , Thesis (MSc) -- Faculty of Pharmacy, Pharmacy, 2017
- Full Text:
- Date Issued: 2017
Studies in marine diterpene chemistry
- Van Wyk, Albert Wynand Wincke
- Authors: Van Wyk, Albert Wynand Wincke
- Date: 2008
- Subjects: Natural products Diterpenes Mollusks Marine metabolites Chemical oceanography
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4354 , http://hdl.handle.net/10962/d1005019
- Description: This thesis comprises both a natural product investigation and a synthetic component. The natural product investigations are presented in Chapters Two and Three. In Chapter Two the isolation and spectroscopic identification of the new isocopalane diterpene 12S,13R,14Sisocopalan- 13-ol-12,14-diacetate (2.1) and two known 3-(14S)-isocopal-12-ene-15-oyl-1- acetyl-sn-glycerol (2.2) and 3-(14S)-isocopal-12-ene-15-oyl-2-acetyl-sn-glycerol (2.3) from a single, large, unidentified sub-Antarctic nudibranch, collected near Marion Island, approximately 2000 km south of Cape Town are described. Chapter Three discusses the isolation, spectroscopic structure elucidation and anti-oesophageal cancer activity (3.1-3.4 only) of two known labdane diterpenes 6β,7α-diacetoxylabda-8,13E-dien-15-ol (3.1) and 2α,6β,7α-triacetoxylabda-8,13E-dien-15-ol (3.2) and one new 6β,7α,15-triacetoxylabda 8,13E-diene (3.3), as well as new 3α,11-dihydroxy-9,11-seco-cholest-4,7-dien-6,9-dione (3.4) and cholest 7-en-3,5,7-triol (3.5) from the endemic pulmonate mollusc, Trimusculus costatus. The absolute configuration of 3.2, and hence 3.1 and 3.3 (from biogenetic arguments) was determined through X-ray diffraction of a single crystal of the camphanate ester of 3.2. The absolute configuration of the secondary hydroxyl at C-3 of 3.4 was established using the Modified Mosher’s method. The synthetic component of the thesis commences in Chapter Four with the semi-synthesis of labdane diterpene nitriles 9α-cyano-15,16-epoxy-7β-hydroxylabda-13(16),14-dien-6-one (4.1), 9α-cyano-15,16-epoxy-7-hydroxylabda-7,13(16),14-trien-6-one (4.2) and 9α-cyano-15,16- epoxy-6β,7β dihydroxylabda-13(16),14-diene (4.3) from the terrestrial labdane diterpene, hispanolone (4.4). This work is an extension of previous synthetic studies directed towards the synthesis of T. costatus metabolites. Diterpenes 4.1-4.3 exhibited in planta activity against the economically important crop pathogens, Magnaporthea grisea and Puccinia recondita. Chapter Five describes the successful semi-synthesis of two isomeric marine molluscan labdane diterpene aldehyde metabolites, labd-13E-ene-8β-ol-15-al (5.1) and labd-13Z-ene- 8β-ol-15-al (5.2) from the commercially available, terrestrial plant derived, labdane diterpene manool (5.3). Diterpenes 5.1 and 5.2, originally isolated from the Mediterranean nudibranch,Pleurobranchaea meckelii and selected diterpenes arising from this synthesis were evaluated for their activity against an oesophageal cancer cell line (WHCO1). Chapter Six further develops the research discussed in Chapter Five, where ethyl 17-norabiet-13(15)-E-en-8β-ol- 16-oate (5.49) and ethyl 17-norabiet-13(15)-Z-en-8β-ol-16-oate (5.50) were first semisynthesized serendipitously. Based on their structural relationship to naturally occurring tricyclic diterpenes with anti-plasmodial activity, tricyclic diterpenes, 17-norpimaran-13α- ethoxy-8,16-olactone (6.6), 17-norisopimar-15-ene-8β,13β-diol (6.7), 17-norisopimarane- 8β,16-diol (6.8) and 17-norabiet-13(15)-ene-8β,16-diol (6.9) were semi-synthesized from the terrestrial labdane diterpene, 5.3, and critically evaluated for their antimalarial potential from parasite inhibition and haemolytic studies.
- Full Text:
- Date Issued: 2008
- Authors: Van Wyk, Albert Wynand Wincke
- Date: 2008
- Subjects: Natural products Diterpenes Mollusks Marine metabolites Chemical oceanography
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4354 , http://hdl.handle.net/10962/d1005019
- Description: This thesis comprises both a natural product investigation and a synthetic component. The natural product investigations are presented in Chapters Two and Three. In Chapter Two the isolation and spectroscopic identification of the new isocopalane diterpene 12S,13R,14Sisocopalan- 13-ol-12,14-diacetate (2.1) and two known 3-(14S)-isocopal-12-ene-15-oyl-1- acetyl-sn-glycerol (2.2) and 3-(14S)-isocopal-12-ene-15-oyl-2-acetyl-sn-glycerol (2.3) from a single, large, unidentified sub-Antarctic nudibranch, collected near Marion Island, approximately 2000 km south of Cape Town are described. Chapter Three discusses the isolation, spectroscopic structure elucidation and anti-oesophageal cancer activity (3.1-3.4 only) of two known labdane diterpenes 6β,7α-diacetoxylabda-8,13E-dien-15-ol (3.1) and 2α,6β,7α-triacetoxylabda-8,13E-dien-15-ol (3.2) and one new 6β,7α,15-triacetoxylabda 8,13E-diene (3.3), as well as new 3α,11-dihydroxy-9,11-seco-cholest-4,7-dien-6,9-dione (3.4) and cholest 7-en-3,5,7-triol (3.5) from the endemic pulmonate mollusc, Trimusculus costatus. The absolute configuration of 3.2, and hence 3.1 and 3.3 (from biogenetic arguments) was determined through X-ray diffraction of a single crystal of the camphanate ester of 3.2. The absolute configuration of the secondary hydroxyl at C-3 of 3.4 was established using the Modified Mosher’s method. The synthetic component of the thesis commences in Chapter Four with the semi-synthesis of labdane diterpene nitriles 9α-cyano-15,16-epoxy-7β-hydroxylabda-13(16),14-dien-6-one (4.1), 9α-cyano-15,16-epoxy-7-hydroxylabda-7,13(16),14-trien-6-one (4.2) and 9α-cyano-15,16- epoxy-6β,7β dihydroxylabda-13(16),14-diene (4.3) from the terrestrial labdane diterpene, hispanolone (4.4). This work is an extension of previous synthetic studies directed towards the synthesis of T. costatus metabolites. Diterpenes 4.1-4.3 exhibited in planta activity against the economically important crop pathogens, Magnaporthea grisea and Puccinia recondita. Chapter Five describes the successful semi-synthesis of two isomeric marine molluscan labdane diterpene aldehyde metabolites, labd-13E-ene-8β-ol-15-al (5.1) and labd-13Z-ene- 8β-ol-15-al (5.2) from the commercially available, terrestrial plant derived, labdane diterpene manool (5.3). Diterpenes 5.1 and 5.2, originally isolated from the Mediterranean nudibranch,Pleurobranchaea meckelii and selected diterpenes arising from this synthesis were evaluated for their activity against an oesophageal cancer cell line (WHCO1). Chapter Six further develops the research discussed in Chapter Five, where ethyl 17-norabiet-13(15)-E-en-8β-ol- 16-oate (5.49) and ethyl 17-norabiet-13(15)-Z-en-8β-ol-16-oate (5.50) were first semisynthesized serendipitously. Based on their structural relationship to naturally occurring tricyclic diterpenes with anti-plasmodial activity, tricyclic diterpenes, 17-norpimaran-13α- ethoxy-8,16-olactone (6.6), 17-norisopimar-15-ene-8β,13β-diol (6.7), 17-norisopimarane- 8β,16-diol (6.8) and 17-norabiet-13(15)-ene-8β,16-diol (6.9) were semi-synthesized from the terrestrial labdane diterpene, 5.3, and critically evaluated for their antimalarial potential from parasite inhibition and haemolytic studies.
- Full Text:
- Date Issued: 2008
Programme for conference on education
- Authors: Henderson, Derek Scott
- Date: 1980-06-23
- Language: English
- Type: Text
- Identifier: vital:7409 , http://hdl.handle.net/10962/d1018286
- Full Text:
- Date Issued: 1980-06-23
- Authors: Henderson, Derek Scott
- Date: 1980-06-23
- Language: English
- Type: Text
- Identifier: vital:7409 , http://hdl.handle.net/10962/d1018286
- Full Text:
- Date Issued: 1980-06-23