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Total synthesis of (±)-palauolide, (±)-isolinaridiol and (±)-isolinaridiol diacetate

University of British Columbia

This thesis describes the total syntheses of the sesterterpenoid (±)-palauolide (55) and the diterpenoids (±)-isolinaridiol (64) and (±)-isolinaridiol diacetate (61). In the total synthesis of (±)-palauolide, the decalin substructure was constructed by a copper(I) bromide-dimethyl sulfide catalyzed addition of the Grignard reagent 40 to 3,6-dimethyl-2-cyclohexen-1-one (115), followed by intramolecular alkylation of the resultant chloro ketone 121. The resultant annulation product 114 was converted into the nitrile 112, which was stereoselectively alkylated with ICH₂CH₂CH₂OCH₂OCH₃ to provide the nitrile 173. The latter substance was transformed via a series of reactions into compound 175 which was converted into the α β-unsaturated aldehyde 107. Julia olefination of 107 with the lithium salt of the sulfone 223 provided stereoselectively the triene 216, which was photooxygenated to provide (±)-palauolide (55). In the total syntheses of (±)-isolinaridiol (64) and (±)-isolinaridiol diacetate (61), the bicyclic substance 276 was prepared by following the chemistry developed in the synthesis of (±)-palauolide (55). Conversion of 276 into the aldehyde 234, followed by treatment of this material, under carefully defined conditions, with the anion of the Z-lactone phosphonate 261, provided the Z lactone 279 as the major product. Diisobutylaluminum hydride reduction of 279 yielded (±)-isolinaridiol (64). Bis-acetylation of the latter material provided (±) -isolinaridiol diacetate (61). [Formula Omitted]

Text

2010-10-21

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http://hdl.handle.net/2429/29446

Chemistry

University of British Columbia

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