Studies of Peptide Antibiotics. V. Syntheses of Cyclic Penta- and Decapeptides with the l -Valyl- l -ornithyl- l -leucyl- d -phenylalanylsarcosyl Sequence

Abstract A cyclic decapeptide dihydrochloride cyclo-(l-valyl-l-ornithyl-l-leucyl-d-phenylalanylsarcosyl)2·2HCl, which is an analog of gramicidin S and a cyclic pentapeptide monohydrochloride cyclo-l-valyl-l-ornithyl-l-leucyl-d-phenylalanylsarcosyl·HCl, were synthesized for the purpose of comparing their antibacterial activities with gramicidin S. The cyclic decapeptide dihydrochloride was obtained by hydrogenolysis in the presence of hydrogen chloride of a cyclic benzyloxycarbonyl-substituted decapeptide, which had been prepared by the cyclization of a corresponding linear decapeptide active ester. The cyclization reaction of a linear pentapeptide active ester yielded a mixture of a cyclic benzyloxycarbonyl-substituted pentapeptide as a major component, and a cyclic decapeptide and an unidentified cyclic peptide as minor components. The effects of two cyclic peptide hydrochlorides on bacterial growth were tested. The cyclic decapeptide was as active as gramicidin S; however, the cyclic pentapeptide showed no activity in relation to any of the microorganisms tested.