Biomimetic approach towards alkaloid natural product synthesis and the synthesis of epicocconone analogues with near infra-red fluorescence

Empirical thesis.Includes bibliographical references.Chapter 1. Diastereoselective biomimetic synthesis of natural products mikimopine and cucumopine -- Chapter 2. Biogenesis of the oroidin alkaloids -- Chapter 3. Biomimetic approach towards the synthesis of oroidin alkaloids from their biogenetic precursor(s) -- Chapter 4. Investigation of the bromonium ion route -- Chapter 4. Synthesis of epicconone-hemicyanine hybrids for near infra-red fluorescence -- Chapter 5. Experimental.Nature generates huge diversity in molecular frameworks by using the simplest route, starting from abundantly available precursors. The biogenesis of natural products provides valuable information for the design of efficient routes for complex natural products based on structural analysis and biosynthetic pathways. Chapter 1 investigates the diastereoselective biomimetic synthesis of the natural products mikimopine and cucumopine, based on their biogenesis from the Pictet-Spengler reaction between the naturally abundant precursors !-ketoglutaric acid and L-histidine. Chapter 2 and 3 then focus on the structurally diverse and complex family of natural products, known as the oroidin alkaloids. In Chapter 2, a comprehensive review of the oroidin alkaloids isolated thus far, is first provided. The biogenesis of all the currently known oroidin alkaloids has been analysed and this has led, for the first time, to a unifying theory for their formation in Nature. Haloperoxidase enzymes are thought to play an important role in the biosynthesis of these marine natural products. Taking this into account, our proposed biogenesis explains the formation of every oroidin alkaloid from the reactive intermediate epoxide or bromonium ion of the precursor oroidin or dihydrooroidin, and forms the basis of a biomimetic approach towards the synthesis of these fascinating and biologically active alkaloids. Our efforts towards this, are described in Chapter 3, first by exploring the epoxide route and then the bromonium ion route, and have led to the synthesis of some natural and unnatural oroidin alkaloids. Chapter 4 then moves away from the topic of biomimetic synthesis and describes the synthesis ofhemicyanine hybrids of the fluorescent natural product epicocconone. The photophysical properties of these novel near infra-red dyes are reported and their potential in the detection of biomolecules demonstrated. Finally the experimental andappendices for the whole thesis are provided in Chapter 5 and 6 respectively.Mode of access: World wide web1 online resource (xviii, 376 pages) colour illustration