Several strategies outlining approaches to the synthesis of the heteroanthracyclinones 4-demethoxyxanthodaunomycinone and 4-demethoxyisoxanthodaunomycinone (7,8,9,10-tetrahydrobenzo(b)-6,7,9,11-tetrahydroxy-9-acetylxanthen-12 and 5-one) are described. / The condensation of tetralin 2-acetyl-5,8-dimethoxy-1,2,3,4-tetrahydro-2-naphthol with o-methoxybenzoic acid was investigated and useful large-scale syntheses of important 1,4-dimethoxy-substituted xanthone intermediates were developed. / Diels-Alder cycloaddition reaction between a xanthone-derived o-quinodimethane intermediate and an olefin afforded a low yield of adduct. On the other hand, excellent yields of isolable but labile adducts were obtained in the cycloaddition reaction between xanthoquinone (and also thioxanthoquinone) and Danishefsky's dienes. The formation of linear vs internal adducts was rationalized on the grounds of resonance and FMO theory. Efforts to induce unactivated dienes to cycloadd using catalysts as well as annulation studies on model compounds using the novel reagent (E)-N-vinylpyrrolidine-(beta)-(2-lithio-1,3-dithian-2-yl) (as a synthon of the (alpha),(beta)-dianion of acetaldehyde) are discussed. / The synthesis of daunomycin and xanthodaunomycin analogs carrying a carbon substituent at position 7 were not accessible using the Diels-Alder cycloaddition reaction as diene 1-carbomethoxy-3-triethylsilyloxy-1,3-butadiene failed to react with either quinizarinquinone or xanthoquinone even at elevated temperatures. / The compound 4-hydroxy-1- 2- (2-hydroxyethyl)amino ethyl amino xanthone and the 4-methoxy derivative were prepared and found to be inactive in the in vivo P-388 mouse leukemia model system.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.72059 |
| Date | January 1985 |
| Creators | Mancini, Michael. |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Doctor of Philosophy (Department of Chemistry.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 000227739, proquestno: AAINL24062, Theses scanned by UMI/ProQuest. |
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