Syntheses of Cyclic Decapeptides with Four Ornithyl Residues Related to Gramicidin S

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Abstract
Three cyclic decapeptides with four l-ornithyl residues related to gramicidin S (GS), cyclo(–Orn–Leu–Orn–d-Phe–Pro–)2 (D-L-12), cyclo(–Orn–Leu–Orn–Phe–Pro–)2 (L-L-12), and cyclo(–Orn–Leu–Orn–Phe–d-Pro–)2 (L-D-12), were synthesized to investigate the contribution of increase of the basic amino acid residues and of configurations of phenylalanyl and prolyl residues toward antibacterial activity. These GS-like analogs were synthesized by the solution method of peptide synthesis. Protected cyclic decapeptides were synthesized through a cyclization reaction of linear decapeptide azide in pyridine. Hydrogenolysis of the protected cyclic decapeptides afforded crystalline tetrahydrochlorides of the desired analogs. In the experiment of circular dichroism, D-L-12 gave a curve similar to that of GS, while L-L-12 and L-D-12 gave different curves. Antibacterial assays showed L-L-12 exhibited substantial activities against Gram-negative bacteria, whereas D-L-12 and L-D-12 negligible activity.