Studies of Peptide Antibiotics. XXXIII. Syntheses of Gramicidin S Analogs Containing N-Methyl-l-valine in Place of l-Valine

Two analogs of gramicidin S, [1-N-methyl-l-valine]–gramicidin S and [1,1'-di-N-methyl-l-valine]–gramicidin S, were prepared for the purpose of investigating the contribution of NH group of l-valyl residue in gramicidin S to antibacterial activity. They exhibit weak activity as compared with gramicidin S in the antibacterial test toward microorganisms. The optical rotatory dispersions of these analogs and gramicidin S were measured in ethanol and 8 M urea. It was suggested that both analogs have a different molecular conformation from that of gramicidin S, and that the NH group of valyl residues is necessary for stabilizing the conformation to exhibit biological activity.