No / Mono- and disaccharide-functionalised conjugates of the fluoroquinolone antibiotic ciprofloxacin have been synthesised and used as chemical probes of the bacterial uptake of glycosylated ciprofloxacin. Their antimicrobial activities against a panel of clinically relevant bacteria were determined: the ability of these conjugates to inhibit their target DNA gyrase and to be transported into the bacteria was assessed by using in vivo and in vitro assays. The data suggest a lack of active uptake through sugar transporters and that although the addition of monosaccharides is compatible with the inhibition of DNA gyrase, the addition of a disaccharide results in a significant decrease in antimicrobial activity.

This thesis describes stereospecific fluorination reactions, and addresses the synthesis of fluorosugars. In Chapter 1, the influence of fluorine on the physical properties of organic molecules, as well as its stereoelectronic effects, are introduced. Furthermore, an overview of nucleophilic and electrophilic fluorination reactions is given. Chapter 2 describes the dehydroxyfluorination of allylic alcohol diastereoisomers 155a and 155b, which can proceed either by direct or allylic fluorination. The regio- and stereo- selectivities were also assessed. Chapter 3 outlines the synthesis of the novel trifluoro D-glucose analogue 193 and trifluoro D-altrose analogue 216. The transport of these hexose analogues across the red blood cell membranes was then explored, to investigate the influence of polarity versus hydrogen bonding ability in carbohydrate-protein interactions. Chapter 4 describes the development and optimisation of Bio’s methodology, to promote stereospecific dehydroxyfluorination of benzylic alcohols (R)-213 and (R)-227 by addition of TMS-amine additives 226 and 229. And finally Chapter 5 reports the experimental procedures as well as the characterisation and the crystallographic data of the molecules prepared in this thesis.

Saccharides, a class of organic materials, are potential candidates for nonlinear optical applications. Ascorbic acid is a sugar acid and is classified as a monosaccharide. The molecule of ascorbic acid has two chiral centers and, therefore, four stereoisomers. Among them, two are naturally occurring compounds; L-ascorbic acid and D-isoascorbic acid. From these two acids various salts and other derivatives could be synthesized. In this thesis, four compounds of the ascorbic acid family were selected for detailed study based on their nonlinearity, chemical and physical stability and their crystallization characteristics. The thesis is organized into seven chapters. The first chapter covers the theoretical background of nonlinear optics, especially, second harmonic generation. Second chapter details the experimental techniques and methodology adopted. Chapter 3 discusses the crystal structure, growth, physical and nonlinear optical properties of Lithium Disoascorbate monohydrate (LDAM). Detailed analysis of refractive index measurements employing Brewsters angle method and determination of phase matching curves, effective nonlinear coefficient, walk off angle etc are given. In Chapter 4, investigations on Sodium D-isoascorbate monohydrate (NDAM) are presented. Detailed characterization of the crystals including thermal, optical, dielectric properties are carried out. Analyses of dielectric dispersion based on Cole-Cole equation are discussed. Comprehensive studies on laser damage of the crystals are discussed. Chapter 5 discusses the nonlinear optical properties of the monoclinic D-isoascorbic acid (DIA). Chapter 6 presents studies on the triclinic Lithium L-ascorbate dihydrate (LLA) crystals. The crystals exhibit intense non-collinear second harmonic rings as they possesses large birefringence coupled with high second order nonlinear coefficients. The SHG conversion efficiency of these crystals is 15 times that of KDP. In the final chapter, a comprehensive summary of the work carried out is presented along with scope for further investigations.