This thesis describes a new method for the synthesis of pseudodisaccharides containing a carbasugar analogue attached to a "true" sugar. The methodology is based on a Diels-Alder cycloaddition of vinyl sugars and appropriately substituted pyran-2-ones, followed by chemical manipulation of the resulting cycloadducts. The thesis also describes the synthesis of inhibitors of Golgi α-mannosidase II and glucokinase. The first chapter is a comprehensive survey of the reported synthetic routes to pseudodisaccharides from the literature. The results and discussions are presented in chapter 2. This chapter starts by discussion of the preparation of vinyl sugars and pyran-2-ones and the regio- and stereoselectivity of their cycloadditions. This is followed by reporting the chemical manipulations of these cycloadducts and the synthesis of a pseudodisaccharide. Cycloadducts are shown to lose carbon dioxide at elevated temperatures to afford dihydrobenzenes. The loss of the bridging carbon dioxide from the cycloadducts is experimentally and computationally investigated. The resulting dihydrobenzenes are shown to also be useful as precursors in the synthesis of pseudodisaccharides. The chemical manipulation of these dihydrobenzenes is used towards the synthesis of a pseudodisaccharide. The third and fourth chapters focus on the synthesis of new inhibitors of Golgi α-mannosidase II and glucokinase respectively. A range of 6-aminoglucose and mannose derivatives were prepared and tested for the inhibition of Jack bean α-mannosidase, but were found to lack any inhibition. Similarly, a range of 6-triazologlucose derivatives were prepared but were found to lack any cytotoxicity. The fifth chapter contains the details of the preparation, experimental procedures and spectroscopic characterisation of the synthesised chemical compounds. Rate calculations are reported in Appendix I and the X-ray crystallographic data are presented in the Appendix II.

This thesis describes a new method for the synthesis of pseudodisaccharides containing a carbasugar analogue attached to a "true" sugar. The methodology is based on a Diels-Alder cycloaddition of vinyl sugars and appropriately substituted pyran-2-ones, followed by chemical manipulation of the resulting cycloadducts. The thesis also describes the synthesis of inhibitors of Golgi ¿-mannosidase II and glucokinase. The first chapter is a comprehensive survey of the reported synthetic routes to pseudodisaccharides from the literature. The results and discussions are presented in chapter 2. This chapter starts by discussion of the preparation of vinyl sugars and pyran-2-ones and the regio- and stereoselectivity of their cycloadditions. This is followed by reporting the chemical manipulations of these cycloadducts and the synthesis of a pseudodisaccharide. Cycloadducts are shown to lose carbon dioxide at elevated temperatures to afford dihydrobenzenes. The loss of the bridging carbon dioxide from the cycloadducts is experimentally and computationally investigated. The resulting dihydrobenzenes are shown to also be useful as precursors in the synthesis of pseudodisaccharides. The chemical manipulation of these dihydrobenzenes is used towards the synthesis of a pseudodisaccharide. The third and fourth chapters focus on the synthesis of new inhibitors of Golgi ¿-mannosidase II and glucokinase respectively. A range of 6-aminoglucose and mannose derivatives were prepared and tested for the inhibition of Jack bean ¿-mannosidase, but were found to lack any inhibition. Similarly, a range of 6-triazologlucose derivatives were prepared but were found to lack any cytotoxicity. The fifth chapter contains the details of the preparation, experimental procedures and spectroscopic characterisation of the synthesised chemical compounds. Rate calculations are reported in Appendix I and the X-ray crystallographic data are presented in the Appendix II.

Diels-Alder cycloaddition of methylcyclopentadienes to 2,5-dibromo-p-benzoquinone was performed. A single, isomerically pure cycloadduct was isolated, whose structure was assigned via analysis of its 1-D and 2-D NMR spectra. Diels-Alder cycloaddition of methylcyclopentadienes to 2 -methoxy-p-benzoquinone was performed. A single, isomerically pure cycloadduct was isolated, whose structure was assigned via analysis of the 1-D and 2-D NMR spectra of this cycloadduct and its reduction product obtained via stereo-specific reduction with sodium borohydride in the presence of cerous chloride. The structure of Thiele's ester was assigned via analysis of its 1-D and 2-D NMR spectra.

An efficient approach to the hydrobenzofuro[3,2-b]chromenone core of sanggenon-type natural products has been developed. The key transformation involves a protecting group-free double rearrangement of a bis-allyloxyflavone ether substrate. A sequence involving asymmetric 3-allyl rearrangement followed by aromatic Claisen rearrangement has been established for the asymmetric synthesis of the hydrobenzofuro[3,2-b]chromenone core structure. This methodology has been successfully applied to asymmetric syntheses of both sanggenol F and sanggenon A. Efficient chiral, racemic syntheses for sanggenons C and O have been achieved. The key transformation entails a biomimetic Diels-Alder cycloaddition between a flavonoid diene and a 2'-hydroxychalcone. The flavonoid diene was produced from a protected flavonoid chromene via isomerization. Metal-catalyzed alkynyl Claisen (Saucy-Marbet) rearrangements of 3-alkynyl flavone ethers have been evaluated, and a 1,2-acyl migration cascade which afforded novel furanyl benzofuranone scaffolds was discovered. Mechanistic studies have revealed that the rearrangement is likely initiated by 5-endo enyne cyclization to a platinum-containing spiro-oxocarbenium intermediate, which may be intercepted by methanol to produce a spirodihydrofuran or further rearranged to afford allenyl chromanediones and benzofuranones at higher reaction temperature. Lewis acid-catalyzed [1,3]-rearrangements of 3-aryl substituted flavone ethers have also been developed.

Yes / An experimental and computational investigation is conducted into the role of substituents in retro Diels-Alder extrusion of CO2 from 2-oxa-bicyclo[2.2.2]oct-5-en-3-ones. We provide the first experimental evidence that loss of CO2 from the cycloadducts significantly depends on the nature and position of the substituents. For example, we show that whilst 5-carboethoxy-2-pyrone undergoes a more facile cycloaddition that 3-carboethoxy-2-pyrone, the cycloadduct from the latter pyrone undergoes a more facile loss of CO2 than the cycloadduct from the former pyrone. / EPSRC, Yorkshire Cancer Research, Yorkshire Enterprise Fellowships