Synthetic approaches towards novel indole alkaloids

This thesis describes several synthetic approaches to some novel indole alkaloids. The Introduction (Chapter One) outlines the need for continuous discovery of new antibiotics in todays environment. The family of Kinamycin antibiotics is described along with their biosynthesis and the evidence of the novel biosynthetic precursor known as Pre-Kinamycin. Chapter Two (2.1) deals with a retrosynthetic analysis leading to a study of Tandem Directed Ortho-Metallation reactions and a proposed synthesis of Pre-Kinamycin. Section 2.2 describes the study of stable analogues of indole-2,3-quinodimethane and the Dials–Alder reactions thereof. Also Dials-Alder reactions of pyrano[3,4-b]indol-3-ones with benzyne and the subsequent manipulation of the carbazole-based products are detailed. Section 2.3 outlines the study of the Friedel–Crafts acylation reaction with respect to the indole nucleus and the application of such a reaction to the synthesis of the Pre-Kinamycin skeleton. Investigations into acid mediated cyclisations to form quinones and the use of Weinreb amides as acylating agents are also described. Chapter Three (3.1) examines the problems of iron overload diseases (haemochromatosis) and the efforts to produce effective iron chelators. Section 3.2 describes the discovery of four novel indole alkaloids known as Uvarindoles and their possible consideration as iron chelators. Section 3.3 examines two retrosynthetic analyses towards Uvarindole B and the investigation into the synthesis thereof, involving similar methodology as that developed in section 2.3. Chapter Four describes the relevant experimental details for the intermediates described in sections 2.1 through 3.3 and the respective spectroscopic data obtained. Chapter Five gives the references for all the relevant work quoted in above sections.