Studies of Peptide Antibiotics. XII. Syntheses of [2,2′-α,γ-Diaminobutyric acid]- and [2,2′-Lysine]-gramicidin S

Abstract
To investigate the contribution for the antibacterial activity of the ornithine residues in gramicidin S, two analogs of gramicidin S, [2, 2′-l-α,γ-diaminobutyric acid]- and [2, 2′-lysine]-gramicidin S, were synthesized by the cyclization reaction of linear pentapeptide active esters with pyridine. It was indicated that the crude product of the cyclization of each of the linear active esters was composed of two components. The protected cyclic decapeptide, a less soluble material, was easily isolated by fractional crystallization, and the hydrogenolysis of this product in the presence of hydrogen chloride afforded the crystalline hydrochloride of [2, 2′-diaminobutyric acid]-or [2, 2′-lysine]-gramicidin S. These cyclic decapeptides were as active as natural gramicidin S; the results indicated that the side chains of the ornithines in gramicidin S could be replaced by other chains without a loss of activity.