The synthesis of alkaloids from enaminones has been used extensively in the University of the Witwatersrand’s organic chemistry laboratories. In this thesis enaminone precursors are one of the main ways of accessing lamellarin analogues. The lamellarin alkaloids are an important family of marine alkaloids, owing to their vast biological properties. A brief background to marine alkaloids and their general potential is given, followed by a review of lamellarin alkaloids, their structural and biological properties and some of the major syntheses carried out over the past few years. Two novel features form the basis of the synthetic methods described in the thesis. The first is an approach to forming the lamellarin alkaloids from enaminone precursors, which are prepared through the Eschenmoser sulphide contraction. The second method uses a novel pyrrole formation, which was initially conceptualized by Garreth L. Morgans in his PhD thesis (2008). The main target of the investigation was lamellarin G trimethyl ether. In Chapter 3, the syntheses of a range of mono-, di- and tetra-substituted phenacyl halides are discussed. The phenacyl halides were used in the preparation of various enaminone precursors. The tetrasubstituted phenacyl halide 2-bromo-1-(2-hydroxy-4,5-dimethoxyphenyl)ethanone 3.17 is required for the synthesis of our target lamellarin G trimethyl ether. The phenacyl halides are important in both the model synthesis described in Chapter 4 and the synthesis toward lamellarins in Chapter 5. Chapter 4 deals mainly with the synthesis of pyrrolizine systems. Methodology is described for the preparation of a variety of enaminones, pyrroles and tetracyclic lamellarin analogues. The closest pyrrolizine system to lamellarin G trimethyl ether, 11-(3,4-dimethoxyphenyl)-2,3-dimethoxy-9,10-dihydrochromeno[4,3-b]pyrrolizin-6(8H)-one 4.52, was the final and most complex tetracyclic model structure analogous to lamellarin G trimethyl ether. Indolizine and pyrroloazepine adaptations were also demonstrated and tetracyclic systems 10,11-dihydro-8H-chromeno[3,2-a]indolizin-12(9H)-one 4.39 and 9,10,11,12-tetrahydrochromeno[3',2':3,4]pyrrolo[1,2-a]azepin-6(8H)-one 4.40 were successfully prepared, even though the pyrrole formed in an unexpected way. Finally in Chapter 5, the methodology established in the model study was used in the attempted synthesis of lamellarin G trimethyl ether. A second method was also investigated. Thus, various N-alkylated and N-H enaminones were successfully synthesized, from which novel and unexpected pyrrole-containing products 8-(3,4-dimethoxyphenyl)-2,3-dimethoxy-5H-chromeno[3',2':3,4]pyrrolo[2,1]isoquinolin-14(6H)-one 5.28 and (3-ethoxy-8,9-dimethoxy-2-phenyl-5,6-dihydropyrrolo[2,1-a]isoquinolin-1-yl)(phenyl)methanone 5.37 were formed, even though our desired product lamellarin G trimethyl ether could not be attained from either method.

by Cui Yanyan. / "June 1999." / Thesis (Ph.D.)--Chinese University of Hong Kong, 1999. / Includes bibliographical references (p. 154-163). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstracts in English and Chinese.

The akuammiline alkaloids are an intriguing class of natural products that display an array of biological activities and structural diversity. Despite being known for over 125 years, it is surprising that these complex monoterpene indole alkaloids have only recently elicited sustained interest from the synthetic community, especially given the storied history of this broad family in the development of the art of total synthesis, and, in particular, heterocyclic chemistry. This dissertation details our efforts to address these deficiencies through work directed at the unique akuammiline alkaloid (+)-scholarisine A, ultimately yielding a concise and enantiospecific preparation of this challenging target. Building on this initial success, we have initiated studies aiming to generalize these strategies to the akuammiline class as whole, efforts that have been empowered by the development of several novel synthetic transforms. These investigations have culminated in the efficient synthesis of a collection of advanced intermediates en route to the varied frameworks represented by strictamine and 10-demethoxynorvincorine. In addition, we have leveraged our expertise gained within these challenging contexts towards a method with utility beyond the akuammiline class, one that is likely to find broad application in both natural product synthesis and the assembly of medicinally-relevant building blocks.

Thesis (Ph.D.)--Ohio University, March, 2008. / Abstract only has been uploaded to OhioLINK. Includes bibliographical references (leaves 145-160).

Thesis (M.S.)--Brigham Young University. Dept. of Chemistry and Biochemistry, 2006. / Includes bibliographical references.

M.Sc. (Chemistry) / The aim of this study was to investigate alternative routes for the stereocontrolled synthesis of hydroxylated indolizidine, piperidine and pyrrolidine alkaloids, starting from monosaccharides as chiral building blocks. This study was not aimed at improving consisting routes - it was rather aimed at developing new routes towards the synthesis of these alkaloids. Mixed results were obtained in the investigation into alternative routes for the synthesis of the bicyclic poly hydroxylated indolizidine alkaloids, but a new and efficient stereospecific synthesis of polyhydroxylated piperidine- and pyrrolidine alkaloids were developed. The aims and results can be summarised in more detail as follows: a. Stereospecific synthesis of castanospermine. The synthesis of this medium sized nitrogen-containing bicyclic molecule was approached in a unique way. The utilization of bifunctional Wittig- and Wittig-Horner reagents containing nitrogen functionalities was considered promising for the aims of this study. By the usage of known reactions, e.g. Wittig, Wittig-Horner, Schiff-base and Aza-Wittig reactions, it was foreseen that these bifunctional reagents could be coupled in two concurrent steps to dicarbonyl compounds to form a nitrogen containing rings. Several nitrogen containing Wittig reagents were prepared. At the one end of these reagents a phosphonate or phosphine group furnished the phosphorus moiety while the other end of these reagents comprised the nitrogen moiety by reduction of a nitrile group or azide displacement of a leaving group. No coupling was obtained between these bifunctional reagents and a dicarbonyl compound derived from D-glucose and the influence of two functional groups in such close proximity in the Wittig reagent is being further investigated. Coupling was, however, achieved by the utilization of an alternative bifunctional reagent in which a Wittig-Horner reaction was used. The successful implementation of this unique methodology in the synthesis of medium size nitrogen containing ring is being further investigated.

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published_or_final_version / Chemistry / Doctoral / Doctor of Philosophy

No description available.

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