Approaches to the Total Synthesis of the Complanadines

Abstract

In this thesis is presented work carried out during the course of the last 42 months. It concerns approaches towards total syntheses of the complanadine alkaloids. The main focus is the development of a model system to establish the viability of the key step in our proposed route to the complanadines. The thesis is divided into five chapters. Chapter 1 is an introduction to the complanadines, their biological activity and accomplished total syntheses to date. A brief introduction to the Diels–Alder reaction and selected examples of its application in the total syntheses of natural products are given. The Kondrat’eva oxazole–olefin hetero-Diels–Alder reaction as a method of pyridine formation is described and its application in the total synthesis of natural products is reviewed. Chapter 2 is the first part of the results and discussion section. It details our retrosynthetic analysis of complanadine A, outlines the corresponding proposed forward synthesis and presents a model system designed and synthesised to test the applicability of the Kondrat’eva oxazole–olefin hetero-Diels–Alder reaction in the context of our proposed total synthesis. Chapter 3 discusses work carried out in approaches to the total synthesis of complanadines and their monomeric subunit, lycodine, by means of the methodology developed in the previous chapter. Chapter 4 is the experimental section, which gives descriptions of the synthetic procedures employed and spectroscopic data for all compounds synthesised, both novel and previously reported, as discussed in Chapter 2 and Chapter 3. Supplementary information such as X-Ray data for synthesised compounds and selected NMR spectra are enclosed in the appendices.

Date of Award	27 Jul 2012
Original language	English
Awarding Institution	University of Bath
Supervisor	Simon Lewis (Supervisor) & Jonathan Williams (Supervisor)