Novel organofluorine chemistry : nucleophilic fluorinating agents and potential anticancer compounds

• Main Author: Patterson, Richard
• Published: Cardiff University 2006
• Subjects: 547.02
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.583852

This thesis covers work investigating the effects of fluorine incorporation on the structure, biological activity, and NMR properties of anticancer chalcones as well as novel methods for the inclusion of fluorinated moieties into organic compounds. The first chapter looks at the use of silanes as carriers of small fluorinated nucleophiles which can be activated by fluoride anion catalysis to deliver such nucleophiles to organic electrophiles such as aldehydes. The synthesis of a group of such silanes and an assessment of their reactivity towards aromatic aldehydes is described. The second and third chapters describe the synthesis and compare the structures and biological activities of four series of chalcones; chapter two looks at chalcones which have non fluorinated groups (a nitrile group and an ethyl ester group) on the alpha position and chapter three looks at chalcones which have F and CF3 groups on that position. A comparison of the effects of substitution, at both the alpha position and on the B ring, on structure and cytotoxicity of these compounds is given. Several of the fluorinated chalcones were found to be highly cytotoxic and further assessment of their tubulin-binding properties was carried out. Chapter four looks at some unusual, long range fluorine-hydrogen coupling interactions which have been observed in the NMR spectra of certain types of chalcones. The effects of various substitutions and structural changes on these coupling patterns are examined. In addition a brief study into the dimerisation of chalcones is described. The final chapter looks at the use of FAR type reagents to generate asymmetric fluorinated amides using secondary chiral amines. Synthesis of a number of chiral amines praline and their addition, with limited success, to trifluorovinyl styrenes is discussed.