Studies in Natural Products Synthesis

Abstract

The pyrrolophenanthridinone-containing Amaryllidaceae alkaloids, representative examples of which include hippadine, lycoranine A, lycoranine B and 2-methoxypratosine, often display a wide range of biological activities that are attributed to its core structure. As such, studies on their syntheses have been pursued by a number of research groups. The opening chapter of this thesis provides general introduction to the pyrrolophenanthridinone-containing natural products and previous synthetic studies in the area. The research work presented in Chapter Two describes the first total syntheses of three pyrrolophenanthridinone-containing Amaryllidaceae alkaloids, namely lycoranine A, lycoranine B and 2-methoxypratosine, using two related synthetic pathways that only differ in the polarity of the intermediates involved in pivotal Suzuki-Miyaura cross-coupling reactions. The superior one involved iridium-catalysed C–H borylation of the appropriate indoles to generate 7-borylindoles and the Suzuki-Miyaura cross-coupling of these with the relevant bromobenzoate. Based on the aforementioned successes in using iridium-catalysed C–H borylations of indoles during natural product synthesis, studies on such processes were extended to indolines. Specifically, then, Chapter Three details the work carried out on the iridium-catalysed C–H borylation of various indolines, as well as synthetic approaches to the indoline-containing natural products, lycosinine A, lycosinine B and lycosprenine. The synthesis of lycosinine A was completed over three steps that involve an iridium-catalysed C–H borylation reaction, a Suzuki-Miyaura cross-coupling reaction and a reductive methylation process. The work presented in Chapter Four details the author’s studies on the preparation of propargyl ether, a potential substrate for participation in a palladium-catalysed intramolecular Alde-ene (IMAE) reaction leading to the hexahydrobenzofuran that embodies key structural features associated with the natural product pleurospiroketal A. The final Chapter (Five) presents all of the experimental procedures and data associated with the compounds prepared during the course of the research work presented in this thesis. Show more