Convergence Leads to Success: Total Synthesis of the Complex Nonribosomal Peptide Polytheonamide B


  • The author thanks the Deutsche Forschungsgemeinschaft (SFB 803 “Functionality controlled by organization in and between membranes”) and the Fonds der Chemischen Industrie (Sachkostenzuschuss) for financial support.


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Beyond the ribosome: The highly cytotoxic 48 residue nonribosomal peptide polytheonamide B, proposed to act as an ion channel, was synthesized by the coupling of four building blocks. The assembly of these peptide segments required the synthesis of eight nonproteinogenic amino acids, including a unique sulfoxide. This first synthetic route towards polytheonamide B (see scheme) demonstrates the potential of state-of-the-art peptide chemistry.