The preparation of possible prodrugs for cancer chemotherapy
dc.contributor.author | Rendle, P. M. | en |
dc.date.accessioned | 2012-12-02T21:25:49Z | |
dc.date.available | 2012-12-02T21:25:49Z | |
dc.date.issued | 1997 | en |
dc.description.abstract | This thesis concerns the design and preparation of compounds which are relevant to a new strategy for the selective chemotherapeutic treatment of tumour cells. These bridged polycyclic compounds are prepared by Diels-Alder chemistry involving cyclic dienes. The bridge is to be cleaved at the cancer site by tumour-selective chemistry acting on an appropriate trigger. This activation of a low toxicity 'prodrug' results in the formation of a planar, aromatic structure which is a characteristic of known anti-cancer drugs (intercalating agents). The crucial step in the organic synthesis of these potential prodrugs is a DielsAlder reaction involving two classes of diene, 1-(methylthio)isobenzofurans and pyranones, with various dienophiles. Examination of this step started with the reaction of 1,1-bis(methylthio)ethene with various pyranones. Stable adducts were isolated from its reaction with methyl coumalate and a benzopyranone; but only substituted carbazoles were observed from the reaction with pyrano[3,4-b]indol-3-ones. An investigation into the thermal stability of the isolated adducts resulted in the observation of an unusual [1,]-methylthio migration. In comparison to 1, 1 bis(methylthio)ethene, 1-(methylthio)-1-(p-tolylsulfonyl)ethene was observed to have lower reactivity and regioselectivity upon reaction with electron-deficient pyranones. The resulting adducts were unstable due to the facile elimination of p-toluenesulfinic acid and only aromatic products were isolated. Diels-Alder adducts were isolated from the reaction of 1-(methylthio)-1-(p-tolylsulfonyl)ethene with 1-(methylthio)isobenzofurans, but they were of low stability and of mixed regio- and stereo- chemistries. The reaction of arynes with 1-(methylthio)isobenzofurans was also investigated. The Diels-Alder reaction between 3,4-didehydropyridine and a protected 1-(methylthio)isobenzofuran resulted in the preparation of a precursor of a tricyclic hetero-aromatic compound, namely the known biologically active compound, 2-azaanthraquinone. | en |
dc.identifier.uri | http://hdl.handle.net/10092/7259 | |
dc.identifier.uri | http://dx.doi.org/10.26021/7457 | |
dc.language.iso | en | |
dc.publisher | University of Canterbury. Chemistry | en |
dc.relation.isreferencedby | NZCU | en |
dc.rights | Copyright P. M. Rendle | en |
dc.rights.uri | https://canterbury.libguides.com/rights/theses | en |
dc.title | The preparation of possible prodrugs for cancer chemotherapy | en |
dc.type | Theses / Dissertations | |
thesis.degree.discipline | Chemistry | en |
thesis.degree.grantor | University of Canterbury | en |
thesis.degree.level | Doctoral | en |
thesis.degree.name | Doctor of Philosophy | en |
uc.bibnumber | 595628 | en |
uc.college | Faculty of Science | en |
Files
Original bundle
1 - 1 of 1