published_or_final_version / Chemistry / Doctoral / Doctor of Philosophy

PART I. The preparation of (-)-ibogamine (1) in fourteen steps from benzoquinone and in 10% overall yield is a powerful illustration of the value of the asymmetric Diels-Alder reaction as a starting point in a multistep synthesis. All four cycloadducts, 70, 77, 84 and 96, obtained with the (S)-BINOL-TiCl��� complex were found to have the same absolute configuration. Furthermore, they are in the same enantiomeric series that Mikami observed with 1,4-naphthoquinone using the same catalyst, lending confidence to future stereochemical predictions that may be made with this system. PART II. Three different routes for the synthesis of the hexahydroisoquinoline 98 met obstacles which defeated our approach to koumine. The Diels-Alder reaction of cyclic 1-azadienes 102 and 108 was abandoned due to the lack of reactivity of the dienes. An anionic oxy-Cope rearrangement of the azabicyclo[2.2.2]octane system caused mainly decomposition of the starting materials. Finally, an intramolecular [2+2] photocycloaddition generated "crossed", "straight" and hydroisoquinoline products in varying ratios, depending on the substituent pattern of the substrate, but this approach was not synthetically useful. The results from this last study may be valuable for predicting the regiochemical outcome of certain intramolecular photocycloadditions. / Graduation date: 2003

published_or_final_version / Chemistry / Master / Master of Philosophy

published_or_final_version / Chemistry / Doctoral / Doctor of Philosophy

Typewritten / 153 leaves / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (Ph.D.)--University of Adelaide, Dept. of Organic Chemistry, 1962

published_or_final_version / Chemistry / Doctoral / Doctor of Philosophy

published_or_final_version / Chemistry / Doctoral / Doctor of Philosophy

A dissertation submitted to the Faculty of Science, University of the Witwatersrand, Johannesburg, in fulfilment of the requirements for the degree of Master of Science. January 1996. / Aspects of the literature of the ant venom alkaloid monomorine I and its stereoisomers were reviewed. Racemic 5-butyl-2-pyrrolidinone was synthesised in two steps from methyl acrylate and 1-nitropentane, A thionation step yielded 5-butylpyrrolidine-2-thione. The Michael addition reaction between 5-butylpyrrolidine-2-thione and ethyl crotonate proceeded with difficulty to form a separable mixture of diastereomers of 5-butyl-l-(2-ethoxycarbonyl-l-methylethyl) pyrrolidine-2-thione. [Abbreviated Abstract. Open document to view full version] / AC2017

This thesis describes the application of the Sonogashira coupling reaction to access a variety of 5-and 7-azaindoles derivatives. The background chapter paints a picture about the importance of indole-containing compounds and azaindole-containing compounds. In this first chapter, discovery, synthesis, properties and reactivity of indole and azaindoles were explained.

This thesis describes a novel total synthesis of (±)-dehalo-perophoramidine (a dehalogenated analogue of the natural product perophoramidine). The key synthetic transformation involves the construction of vicinal quaternary stereocenters which were installed diastereoselectively. A Claisen rearrangement was used to install the first quaternary stereocenter then a Corey-Chaykovsky-type reaction and a Hosomi-Sakurai-type reaction were used to install the second quaternary stereocenter. Investigations directed towards the total synthesis of the communesin family of natural products are also described. In Chapter 1, the natural products perophoramidine and the communesins are introduced and their related biosynthesis is discussed. The isolation, architectural motifs and biological properties of the natural products are described and discussed. Previously reported approaches to perophoramidine and the communesins are reviewed focussing on how the vicinal quaternary stereocenters are formed in each case. Chapter 1 concludes with the retrosynthetic plan used to form dehalo-perophoramidine. In Chapter 2, previous research from the Westwood group is reviewed focusing on an asymmetric Claisen rearrangement which could potentially be used to install a quaternary stereocenter asymmetrically. A previously reported novel Cope rearrangement, potentially useful for a communesin synthesis, is optimised using microwave, neat and high-temperature flow conditions and leads to the synthesis of an intermediate containing two allyl substituents. In Chapter 3, attempts to functionalise selectively the two allyl substituents are described which was eventually achieved by a regioselective iodoetherification reaction. This leads to the synthesis of two relatively advanced intermediates for a communesin synthesis. Although the total synthesis of the communesins was not achieved, a proposed route from the advanced intermediates to the natural products is described. In Chapter 4, a novel method to construct vicinal quaternary stereocenters is disclosed using a Corey- Chaykovsky-type reaction and a Hosomi-Sakurai-type reaction. A regioselective iodolactonisation, analogous to that presented in Chapter 3, is used to functionalise selectively two allyl substituents that culminates in the preparation of a pentacyclic lactam. In Chapter 5, the total synthesis of (±)-dehalo-perophoramidine is completed and its structure is confirmed by a NMR doping experiment with an authentic sample. The biological activity of dehalo- perophoramidine is investigated and compared to that of perophoramidine. Chapter 5 culminates in an attempted synthesis of the natural product perophoramidine using the route that was used to make dehalo-perophoramidine.