Item – Theses Canada

OCLC number
Link(s) to full text
LAC copy
LAC copy
Ly, Tai Wei,1971-
Synthetic studies on terpenoids : total synthesis of the marine natural product nanaimoal : towards the total synthesis of solidago alcohol via an intermolecular Diels-Alder approach.
Ph. D. -- University of Alberta, 2000
Ottawa : National Library of Canada = Bibliothèque nationale du Canada, [2002]
2 microfiches
Includes bibliographical references.
Chapter one of this thesis describes the total synthesis of the marine natural product nanaimoal (1). The key step was the conversion of enone 53 to give bicyclic ketone 60 using a reductive alkylation methodology recently developed in our laboratories. Bicyclic ketone 60 was also synthesized from enone 64 albeit in lower yield. Enone 53 was readily prepared from 'bis'-nitrile 56 as described in Scheme 15. Wittig olefination followed by acid hydrolysis furnished keto nitrile 54. Robinson annulation of keto nitrile 54 using ethyl vinyl ketone as the Michael acceptor then yielded enone 53. Enone 64 was also synthesized following the same route using methyl vinyl ketone as the Michael acceptor. Bicyclic ketone 60 was reduced under the Huang Minlon modification of the Wolff-Kishner reaction conditions to furnish bicyclic diene 42. Regioselective hydroboration followed by oxidation of the ensuing alkylborane species with pyridinium chlorochromate then completed the synthesis of nanaimoal in 15% overall yield. The second chapter reports on our efforts towards the total synthesis of the C-19 oxygenated 'cis'-normal clerodane solidago alcohol (91) using an intermolecular Diels-Alder approach previously developed in our laboratories. Zinc chloride mediated Diels-Alder reaction of dienone 76 with piperylene (2:1 'trans':' cis' mixture) gave keto ester 77 as the major diastereomer. Conjugate addition of lithium dimethylcuprate followed by reduction of the resulting enolate with lithium aluminum hydride then furnished keto alcohol 78. Mesylation followed by debenzylation resulted in the isolation of keto mesylate 99 which was treated with sodium hydride to effect the ring closure to give keto ether 93. Keto ether 93 was also synthesized from benzyl mesylate 79 by the action of sodium iodide in 'N,N'-dimethylformamide at elevated temperature. Wolff-Kishner reduction of keto ether 93 under Huang Minlon modification conditions then gave tricyclic ether 98. Ether ring opening followed by benzoylation then gave bromo benzoate 106 which was oxidized under modified Kornblum oxidation conditions to yield benzoyl aldehyde 107. 1,2-Addition of 3-lithiofuran to the aldehyde moiety of benzoyl aldehyde 107 followed by acetylation gave furyl acetate 113 which was reduced under dissolving metal reduction conditions to yield [Delta]2-isomer (112) of solidago alcohol (91). Rhodium mediated olefin isomerization resulted in the isolation of the [Delta]1-isomer (114 ).