Approaches to the synthesis of pancratistatin and pancratistatin analogues
| dc.contributor.author | Scalzullo, Stefania Margherita | |
| dc.date.accessioned | 2009-07-01T08:36:10Z | |
| dc.date.available | 2009-07-01T08:36:10Z | |
| dc.date.issued | 2009-07-01T08:36:10Z | |
| dc.description.abstract | Pancratistatin is a naturally occurring Amaryllidaceae alkaloid isolated from the bulbs of Pancratum littorale. Pancratistatin has been shown to be capable of inducing apoptosis in several cancer cell lines. Although the biochemical mechanism for the apoptosis is not yet well known, results suggest that pancratistatin could be a very effective non-toxic alternative for anticancer therapy. Nevertheless, further analysis of pancratistatin has been hindered by bioavailability and solubility problems. The aim of this research is to find a viable synthesis of pancratistatin, after which an array of analogues containing a variety of aromatic units can be proposed. The synthesis of pancratistatin began using carbohydrate chemistry for the initial preparation of the key stereochemical cyclitol ring C of pancratistatin. Chapter 2 of this dissertation describes the syntheses of the suitable glucose derived compounds. Previously established carbohydrate chemistry was used to prepare (3aR,5S,6R,6aR)-2,2-dimethyl-6-[(phenylmethyl)oxy]tetrahydrofuro[2,3-d][1,3]dioxole-5-carbaldehyde 104. The aldehyde 104 was used to prepare the nitroalkene 105 and the enoate 106. The Henry reaction was used to synthesize the nitroalkene (3aR,5R,6R,6aR)-2,2-dimethyl-5-[(E)-2-nitroethenyl]-6-phenylmethyl)oxy]tetrahydrofuro[2,3-d][1,3]dioxole 105. Similarly, a Horner-Wadsworth-Emmons reaction was utilized to prepare the enoate methyl (2E)-3-{(3aR,5R,6R,6aR)-2,2-dimethyl-6-[(phenylmethyl)oxy]tetrahydrofuro[2,3-d][1,3]dioxol-5-yl}prop-2-enoate 106. In Chapter 3 of the dissertation, the previously prepared nitroalkene 105 and enoate 106 are used in an array of conjugate addition reactions. The first method utilized organocuprate conjugate addition, while the second method adopted a rhodium(I)-catalyzed conjugate addition. A variety of aromatic substituents were used as the nucleophilic partners namely, phenyl, dioxolylphenyl, benzodioxine, and trimethoxyphenyl. In Chapter 4 of the dissertation, using only the phenyl and dioxolylphenyl substituted compounds, deprotection of the acetonide group was attempted. This was followed by several attempts at ring closure and acetylation reactions, unfortunately without success and no further progress concerning this synthetic strategy could be made. Finally, in Chapter 5 of the dissertation a summary of the results observed for the research project was made. This was followed by the experimental data for the reactions investigated during the project (Chapter 6), and a brief appendix. | en |
| dc.identifier.uri | http://hdl.handle.net/10539/7055 | |
| dc.language.iso | en | en |
| dc.title | Approaches to the synthesis of pancratistatin and pancratistatin analogues | en |
| dc.type | Thesis | en |