Sarah Kappler, Andreas Siebert and Uli Kazmaier* Pages 1 - 7 ( 7 )
Introduction: Miuraenamides belong to marine natural compounds with interesting biological properties.
Materials and Methods: They initiate polymerization of monomeric actin and therefore show high cytotoxicity by influencing the cytoskeleton. New derivatives of the miuraenamides have been synthesized containing a N-methylated amide bond instead of the more easily hydrolysable ester in the natural products.
Results: Incorporation of an aromatic side chain onto the C-terminal amino acid of the tripeptide fragment also led to highly active new miuraenamides.
Conclusion: We could show that the ester bond of the natural product miuraenamide can be replaced by an N-methyl amide. The yields in the cyclization step are high and generally much better that with the corresponding esters. On the other hand, the biological activity of the new amide analogs are lower compared to the natural products, but the activity can significantly be increased by incorporation of a p-nitrophenyl group at the C-terminus of the peptide fragment.
Actin, cyclodepsipeptides, cyclopeptides, cytoskeleton, cytotoxic compounds, myxobacteria, natural products.
Institute of Organic Chemistry, Saarland University, P.O. Box 151150, 66041 Saarbrücken, Institute of Organic Chemistry, Saarland University, P.O. Box 151150, 66041 Saarbrücken, Institute of Organic Chemistry, Saarland University, P.O. Box 151150, 66041 Saarbrücken