A Biomimetic Total Synthesis of Clivonine

Abstract

The first chapter of this thesis discusses the biomimetic total synthesis of clivonine. Clivonine is a member of the Amaryllidaceae family of alkaloids and was isolated from the plant Clivia miniata Regel by Wildman in 1956. Barton first proposed the biosynthesis of the Amaryllidaceae alkaloids in 1958, hypothesising that the key diversifying step in the biosynthesis was an intramolecular phenolic oxidative coupling of a common precursor, norbelladine. However, it was not until 2 years later, in 1960, that Barton was able to account for the biosynthesis of the lycorenine class of the Amaryllidaceae alkaloids, the class in which clivonine is a member. He proposed that a ‘ring-switch’ must occur after the initial intramolecular phenolic oxidative coupling from a lycorine type progenitor to that of a lycorenine type skeleton. Our synthesis of clivonine demonstrates for the first time the synthetic interconversion between these two classes of compounds in a manner that can be considered biomimetic. The second chapter of this thesis details our synthesis of the acetonide protected derivative of cis-3,5-cyclohexadien-1,2-diol. The first section of this chapter highlights the importance of these types of molecules and reviews the previous syntheses of this compound. The second section then details the development of a five-step three-pot synthesis of this compound in an overall 50% yield starting from commercially available 1,3-cyclohexadiene. The final chapter of this thesis discusses the studies towards the development of a catalytic asymmetric retro-Cope elimination reaction. This chapter will first highlight recent advances that have been made towards the asymmetric hydroamination (AHA) reaction before reviewing the recent progress made towards expanding the scope of the retro-Cope elimination reaction. Finally, our proposed method of developing an asymmetric retro-Cope reaction will be outlined, along with details of preliminary studies focussed on the development of a suitable system with which the asymmetric retro-Cope elimination can be studied.