Studies of Peptide Antibiotics. II. Cyclo- l -valyl- l -ornithyl- l -leucyl- d -phenylalanyl- l -prolylglycyl

A cyclic hexapeptide, cyclo-l-valyl-l-ornithyl-l-leucyl-d-phenylalanyl-l-prolylglycyl, was synthesized for the purpose of comparing its antibacterial action, if any, with the cyclopeptide antibiotics, such as gramicidin S, with which it shares several common structural features. Synthesis was achieved by condensation of p-methoxybenzyloxycarbonyl-l-valyl-δ- benzyl-oxycarbonyl-l-ornithine azide with l-leucyl-d-phenylalanyl-l-prolylglycine ethyl ester, followed by treatment of the resulting diacyl hexapeptide ester with alkali to remove the ethyl ester group. The diacyl hexapeptide so derived was converted to the p-nitrophenyl ester by the action of di-p-nitrophenyl sulfite, and after removal of the p-methoxybenzyloxycarbonyl group with trifluoroactetic acid, the hexapeptide p-nitrophenyl ester was transformed to the cyclic benzyloxycarbonyl-substituted hexapeptide by treatment with a large excess of pyridine. The cyclic benzyloxycarbonyl-substituted peptide was hydrogenated in the presence of palladium black to yield the desired cyclic hexapeptide hydrochloride. The effects of the synthesized cyclic peptide on bacterial growth were examined. No antibacterial activities were observed against the microorganisms utilized here.