Studies of Peptide Antibiotics. VIII. Synthesis of Gly4,4′-gramicidin S

Abstract
Gly4,4′-gramicidin S dihydrochloride, cyclo-(l-valyl-l-ornithyl-l-leucylglycyl-l-prolyl)2·2HCl, which is an analog of gramicidin S, was synthesized for the purpose of comparing its antibacterial activity with that of gramicidin S. The cyclization reaction via the linear decapeptide active ester or via the linear pentapeptide active ester yielded the same cyclic benzyloxycarbonyl-substituted decapeptide; this was then converted to Gly4,4′-gramicidin S dihydrochloride by hydrogenolysis. The effect of the Gly4,4′-gramicidin S on bacterial growth was tested; the peptide exhibited weak antibacterial activity against Bacillus Subtilis.