The completion of efforts on the total synthesis of the naturally occurring antitumor antibiotics related to deoxybouvardin and RA-I-VII are detailed and include efforts to address the total synthesis of bouvardin based on implementation of an intramolecular Ullmann macrocyclization reaction for formation of the functionalized 14-memberedcycloisodityrosine subunit. Extensions of the studies to conduct a totalsynthesis of piperazinomycin and to model studies that will establish theirviability for application in the synthesis of the vancomycin class of glycopeptide antibiotics are described. Additional studies on the synthesis, biological evaluation, and conformational properties of deoxybouvardin analogs are detailed and include efforts to experimentally define the conformational properties of the agents and their relationship to the agent biological properties, and the conduct of structure-activity relationships within the newlyassigned deoxybouvardin pharmacophore. The total syntheses of the naturally occurring antitumor antibiotics sandramycin and luzopeptin A-C, E2, cyclic decadepsipeptides, are detailed and studies to systematically evaluate their biological properties are described. The agents constitute effective DNA binding agents that interact with DNA through bifunctional intercalation and complementary minor groove binding. Studies will be pursued to delineate the structural features of the agents contributing to their DNA binding affinityand specificity.
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