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dc.contributor.authorBoyce, Jonathan Henryen_US
dc.date.accessioned2017-10-04T16:50:48Z
dc.date.issued2017
dc.identifier.urihttps://hdl.handle.net/2144/24108
dc.description.abstractPolycyclic polyprenylated acylphloroglucinols (PPAPs) are structurally complex natural products with promising biological activities. These compounds have interesting anticancer and anti-HIV properties as well as other biological activities making them highly attractive synthetic targets. We report a stereodivergent, asymmetric total synthesis of (−)-clusianone in six steps from commercial materials. We have implemented a challenging cationic cyclization forging a bond between two sterically encumbered quaternary carbon atoms. Mechanistic studies point to the unique ability of formic acid to mediate the cyclization forming the clusianone framework. We also present a biosynthesis-inspired, diversity-oriented synthesis approach for rapid construction of PPAP analogs via palladium-catalyzed dearomative conjunctive allylic alkylation (DCAA). These efficient palladium-catalyzed protocols construct the [3.3.1]-bicyclic PPAP core in a single step from their stable aromatic precursors. The first syntheses of 13,14-didehydroxyisogarcinol and garcimultiflorone A stereoisomers are reported in six steps from a commercially available phloroglucinol. Lewis acid-controlled, diastereoselective cationic oxycyclizations enabled asymmetric syntheses of (−)-6-epi-13,14-didehydroxyisogarcinol and (+)-30-epi-13,14-didehydroxyisogarcinol. A similar strategy enabled production of the meso-derived isomers (±)-6,30-epi-13,14-didehydroxyisogarcinol and (±)-6,30-epi-garcmultiflorone A. A convenient strategy for gram scale synthesis of these stereoisomers was developed utilizing diastereomer separation at a later stage in the synthesis that minimized the number of necessary synthetic operations to access all possible stereoisomers. Finally, we report cationic rearrangements of dearomatized acylphloroglucinols leading to the formation of unprecedented PPAP scaffolds. A novel type A [3.3.1]-bicyclic PPAP was produced as a major product and the structure confirmed by X-ray crystallographic analysis. A novel [3.3.1]-bicyclolactone was also produced utilizing an alternative substrate. Efforts will be described to determine the scope of these rearrangements and type A-selective cyclizations.en_US
dc.language.isoen_US
dc.subjectOrganic chemistryen_US
dc.subjectPPAP synthesisen_US
dc.subjectAlkylative dearomatizationsen_US
dc.subjectCationic cyclizationsen_US
dc.subjectClusianoneen_US
dc.subjectNatural productsen_US
dc.subjectSynthesisen_US
dc.titleTotal syntheses of polycyclic polyprenylated acylphloroglucinol natural products and analogs utilizing alkylative dearomatizations and cationic cyclizationsen_US
dc.typeThesis/Dissertationen_US
dc.date.updated2017-08-10T01:13:40Z
dc.description.embargo2018-08-09T00:00:00Z
etd.degree.nameDoctor of Philosophyen_US
etd.degree.leveldoctoralen_US
etd.degree.disciplineChemistryen_US
etd.degree.grantorBoston Universityen_US


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