Studies of Peptide Antibiotics. XVII. Analogs of Gramicidin S Containing Glycine or Alanine in Place of Leucine

In order to investigate the contribution to antibacterial activity of the leucine residues at 3- and 3′-position in gramicidin S, 3,3′-glycine- and 3,3′-L-alanine-gramicidin S (XII-G and XII-A) were prepared and tested for antibacterial properties. A crude product obtained after cyclization of a linear pentapeptide active ester consisted of a protected monomer and a dimer. The pure protected dimer was obtained by a Sephadex LH-20 column from the crude product. Hydrogenolysis of the pure protected dimer afforded the crystalline hydrochloride of XII-G or XII-A. It was found that XII-G showed no activity in any of the microorganisms tested, whereas XII-A exhibited substantial activity though weaker than that of gramicidin S.