Diastereoselective desymmetrisation of cyclic meso-anhydrides and derivatisation for use in natural product synthesis

This thesis describes the development of a new method to desymmetrise meso-succinic and glutaric anhydrides and its application in the synthesis of a fragment of the biologically active natural product rapamycin. It is divided into four chapters: - Chapter one provides an introduction to the concept of desymmetrisation, followed by a literature summary reviewing the history of anhydride desymmetrisation methodology over the past fifty years and application in natural product synthesis. - Chapter two describes the project background more specifically and the original project aims are delineated. - Chapter three presents the results and discussion: proof of concept is followed by application of the method to generate both acid-amide and ester-amide derivatives. Optimisation studies, scope of reaction and theoretical modelling studies are all incorporated within this section. A general background on the natural product rapamycin is then given, and use of the novel desymmetrisation methodology in the synthesis of a fragment of the interesting and challenging natural product is discussed. - Chapter four concludes the thesis and makes some suggestions for future work. - Chapter five provides a formal account of the experimental procedures. References and appendices containing supporting X-ray crystal structure data follow.EThOS - Electronic Theses Online ServiceGBUnited Kingdo