Part I of this thesis describes the development of bioactive small molecules of relevance to the study of the apicomlexan parasite Toxoplasma gondii into useful chemical tools. The research includes the target identification and validation studies, using both chemical and biological methods. Chapter 1 provides an overview of chemical genetics with a particular emphasis on methods for the identification of the protein targets of bioactive small molecules. The concept of biochemical protein target identification techniques was introduced with a detailed discussion of interesting applications from the literature. Chapter 2 focuses on the development of a tetrahydro-β-carboline based lead molecule into a chemical tool through target identification studies. The structure activity relationship (SAR) data associated with this core structure, the design of a chemical inducer of dimerisation (CID) and the synthesis of this CID are discussed in detail. Chapter 3 described work done to identify the potential protein target(s) of Conoidin A. Experiments to assess whether Conoidin A can inhibit a proposed target in vitro are also included. Further optimisation of this structural class to develop more potent inhibitors is discussed in the second part of this chapter. Part II of this thesis describes the development of methods for the synthesis of medium-sized ring containing compounds using oxidative fragmentation and rearrangement strategies. Chapter 5 provides an overview of the existing oxidative fragmentation methodology, with an emphasis on the use of oxidative fragmentation reactions for the synthesis of medium-sized ring systems (8-11 ring atoms). Chapter 6 focuses on using the established oxidative fragmentation method in the oxizino carbazolone system to investigate the diasteroselectivity of this reaction. Possible mechanisms for this transformation are investigated and discussed using both chemical and computational methods. An interesting rearrangement reaction has also been observed during this study. Chapter 7 focuses on developing an asymmetric oxidative fragmentation method, for use in the diazabenz[e]aceathrylenes system. Asymmetric oxidative fragmentation reactions using [Ru(pybox)(pydic)] catalysts are discussed. Attempts to optimise the enantiomeric excesses of the reaction by varying reaction conditions and substituents in the substrate are also included.

The utility of computational study lies not only in rationalizing a chemical phenomenon but also in its predictive value. Broadly, the scope of my research work includes understanding of the structure and bonding of molecules as well as reaction mechanisms using computational techniques. Here I will discuss three research problems where computational results successfully rationalize and predict the experimental outcome. Firstly, we will describe the electronic structure and bonding of all the possible cyclic isomers of B2AlHnm (where n =3D 3 =96 6 and m =3D -2 to 1) = which is isoelectronic to the cyclopropenyl cation.1 A comparative study among all the isomers of homocyclic and heterocyclic three- membered boron and aluminum hydrides has also been done to understand the factors that differentiate their hydride chemistry. We will also discuss about two different approaches to stabilize neutral planar B3R3 rings. In a mechanistic study, we have designed a a priori system which can undergo two competing biradical generating processes, namely the Myers-Saito (MS) and Garratt-Braverman (GB) Cyclizations.2,3 We will present a detailed mechanistic study of both the reactions, which indicates the preference of the GB cyclization over MS cyclization. The theoretical prediction is in agreement with the experimental findings. We will also describe a conformational constraint-based strategy to switch the selectivity from GB to MS/Schmittel pathway.4 In another study, we will talk about a DFT study to illustrate the effect of the a) solvent, b) ancillary ligand, (L) c) leaving group, (Hal) and d) metal (M) on the equilibrium between metal boryl (1) and borylene (2) complexes (Scheme 1).5,6