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dc.contributor.advisorShair, Matthew David
dc.contributor.authorLiau, Brian Bor-Jen
dc.date.accessioned2013-10-08T01:38:32Z
dash.embargo.terms2014-06-07en_US
dash.embargo.terms2014-06-07
dc.date.issued2013-10-07
dc.date.submitted2013
dc.identifier.citationLiau, Brian Bor-Jen. 2013. Total Syntheses of Fastigiatine and the Hibarimicin Aglycons. Doctoral dissertation, Harvard University.en_US
dc.identifier.otherhttp://dissertations.umi.com/gsas.harvard:10831en
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:11148287
dc.description.abstractPart one of this two-part thesis describes my efforts toward the total syntheses of the complex polycyclic alkaloids himeradine A and fastigiatine, which are members of the Lycopodium family of natural products. A cascade reaction sequence featuring a biosynthesis-inspired transannular Mannich reaction was planned to construct the strained and densely functionalized pentacyclic cores of the molecules from acyclic starting materials. After difficulties were encountered in a first-generation synthesis plan toward himeradine A, a second-generation synthesis plan was eventually successful in accomplishing the first total synthesis of fastigiatine via a formal [3+3]-cycloaddition reaction and a retro-aldol tandem transannular Mannich reaction sequence. In part two of this thesis, syntheses of the hibarimicin aglycons, including HMP-Y1, atrop-HMP-Y1, hibarimicinone, atrop-hibarimicinone, and HMP-P1, are reported. These natural products are amongst the largest and most complex type-II polyketides isolated. A novel benzylic fluoride Michael-Claisen reaction sequence was developed to construct the complete carbon skeleton of HMP-Y1 and atrop-HMP-Y1 via a symmetrical bidirectional double annulation reaction. Through efforts to convert HMP-Y1 derivatives to hibarimicinone and HMP-P1, a biomimetic mono-oxidation to desymmetrize protected HMP-Y1 was realized. A bidirectional unsymmetrical double annulation and biomimetic etherification were developed to construct the polycyclic and highly-oxidized skeleton of hibarimicinone, atrop-hibarimicinone, and HMP-P1. Lastly, a pH-dependent rotational barrier about the C2-C2' bond of hibarimicinone was discovered, which provides valuable information for achieving the syntheses of the glycosylated congeners of hibarimicinone.en_US
dc.description.sponsorshipChemistry and Chemical Biologyen_US
dc.language.isoen_USen_US
dash.licenseLAA
dc.subjectOrganic chemistryen_US
dc.subjectNatural Productsen_US
dc.subjectTotal Synthesisen_US
dc.titleTotal Syntheses of Fastigiatine and the Hibarimicin Aglyconsen_US
dc.typeThesis or Dissertationen_US
dash.depositing.authorLiau, Brian Bor-Jen
dc.date.available2014-06-07T07:30:54Z
thesis.degree.date2013en_US
thesis.degree.disciplineChemistryen_US
thesis.degree.grantorHarvard Universityen_US
thesis.degree.leveldoctoralen_US
thesis.degree.namePh.D.en_US
dc.contributor.committeeMemberMyers, Andrewen_US
dc.contributor.committeeMemberRitter, Tobiasen_US
dash.contributor.affiliatedLiau, Brian


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