Synthesis and complexation studies of amino-acid derived macrocycles and ligands

This thesis describes work to synthesise i) a novel class of non-racemic amino acid derived macrocycfes through the Heck reaction and ii) new chiral tridentate nitrogen ligands. The synthesis of known macrocycfes, derived from both valine and proline, has been achieved for further complexation studies. These macrocycles are formed through a Heck coupling of two molecules of an iodo-alkene precursor and contain four nitrogen atoms (two amino and two amido) which are capable of binding. The key steps in the synthesis are the reductive amination of the appropriate amino alcohol with 4-iodobenzaldehyde and a Mitsonobu reaction to introduce the nitrogen for the amide group. An increase in the number of donor atoms in the macrocycfes was predicted to lead to more efficient binding to the macrocycle and therefore lead to further applications. The replacement of the benzyl moiety with a pyridine increases the number of donor atoms to six. The synthesis of pyridine containing macrocycfes derived from proline, valine and phenylalanine has been investigated. A similar synthetic strategy was followed but iodine was introduced through halogen exchange and alternative reaction conditions to the Mitsonobu reaction were investigated. An intermediate during the synthesis of the pyridine based macrocycfes is a small chiral amine which has three nitrogen atoms each in a different environment. It was recognised that these would make interesting ligands and their synthesis has been investigated.EThOS - Electronic Theses Online ServiceGBUnited Kingdo