The Synthesis and Biological Activity of 2'-Fluoro-N-methanocarbathymidine Epimers And An Approach Towards the Synthesis of Morphine

In Chapter 1, the syntheses of 2'-fluoro-N-methanocarbathymidine (2'F-NMC) and arabino 2'-fluoro-N-methanocarbathymidine (ara-2'F-NMC) are detailed. The syntheses of both molecules begin with the simple precursor cyclopenten-1-one. Asymmetry is introduced into the molecule by means of a Corey-Bakshi-Shibata asymmetric reduction. The cyclopropane was installed using a directed Simmons-Smith cyclopropanation reaction. The Michael addition of dibenzylamine with the fluoroenone was observed with good diastereoselectivity. The biological activity of the monomer incorporated oligonucleotides will also be discussed.;In Chapter 2, multiple approaches towards a synthesis of morphine were attempted. A palladium-catalyzed Tsuji-Trost reaction will be featured as an attempt to form the C-ring of morphine's carbon framework. A new palladium-catalyzed cyclopropanation reaction to form vinylcyclopropyl ketones was discovered during this pursuit. Another approach towards synthesizing morphine will feature an attempt to form the C-ring by means of a Diels-Alder reaction. The last approach discussed, will be an attempted oxy-Cope rearrangement reaction to potentially install the quaternary center of morphine.