Synthesis and properties of some cyclodepsipeptides

Dory, Yves Luc (1988) Synthesis and properties of some cyclodepsipeptides. University of Southampton, Doctoral Thesis.

Record type: Thesis (Doctoral)

Abstract

Valinomycin displays the best selectivity for potassium. The structure of valinomycin, a naturally occurring cyclodepsipeptide antibiotic is thoroughly discussed. The structure of the metal ion complexes of valinomycin and analogous cyclopeptides are analysed. The chemistry for building linear depsipeptides having alternating ester and amide bonds is reviewed. Experimental studies directed to the synthesis of linear peptides chosen to have adverse structural features with respect to cyclisation are reported. These critical studies established a satisfactory protocol using pentafluorophenyl esters in conjugation with benzylcarbamates in the key cyclisation. Even in a case of formation of a 36 membered ring from a linear precursor having all centres of an L configuration a 70% was obtained. Cyclisations to give 24 and 48 membered rings were also studied. The technique was applied to the synthesis of two valinomycin analogues containing remote phenyl substituents. The required dodecadepsipeptide linear precursors were prepared and cyclised in good yield. The synthesis of a further target, a valinomycin containing remote aryl substituents was studied. Major advances were made in the establishment of a route to this target. The application of modified valinomycin to the sensing of metal ions is discussed. All the new cyclic peptides reported in this study were examined for their ability to bind metal ions. Those valinomycin analogues having the same configuration as valinomycin are shown by electrochemical studies to bind and transport potassium ion efficiently. These compounds also display the same selectivity for alkali cations and their spectral characteristics are similar to that of the natural antibiotic. (DX86221)

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