Carbon-Carbon Bond Formation via Radical Cyclization and Transition Metal Catalysis
Sammanfattning: Free radical cyclization methodology has been used extensively in synthesis for manipulation of complex molecules such as alkaloids, terpenes, carbohydrates, peptides and nucleic acids. The methodology has emerged as a result of work by physical organic chemists who determined rate constants for the most common radical reactions used in organic synthesis.A novel route to cyclic imines based on 5-exo radical cyclization was explored. The radical precursors were imines prepared from allylamine and readily available a-phenylselenenyl ketones. The synthesis of conformationally constrained bicyclic nucleosides is also reported using 5-exo and 6-exo cyclizations of hexenyl and heptenyl radicals in thymidine nucleosides. The nucleosides were incorporated in a 15mer antisense oligonucleotide via solid-phase oligonucleotide synthesis. The AONs with the modifications were tested for target affinity and stability and compared with the well known LNA modified AONs. The thesis discusses the unique qualities of these novel molecules and presents them as potential candidates for antisense therapeutic agents.Keeping up with the theme of intramolecular carbon-carbon bond formation, microwave induced carbodechalcogenation of chalcogenoanhydrides was explored. Poor generality in these reactions made us turn to transition metal catalysis for Sonogashira cross-coupling reactions using alkyl aryl and diaryl tellurides as coupling partners.
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