Studies of Peptide Antibiotics. X. Syntheses of Cyclosemigramicidin S and Gramicidin S

Abstract
The possibility of the occurrence of benzyloxycarbonyl-substituted cyclosemigramicidin S in the course of the cyclization reaction of a linear-pentapeptide-active ester with pyridine was investigated. It was indicated that the crude product of the cyclization of the linear-active ester was composed of two components. The protected gramicidin S, a less soluble material, was easily isolated by fractional crystallization, while the protected cyclosemigramicidin S, a more soluble material, was isolated by a column chromatography of Sephadex LH-20. The hydrogenolyses of these products in the presence of hydrogen chloride afforded the crystalline hydrochlorides of gramicidin S and cyclosemigramicidin S. The cyclic decapeptide was as active as the natural gramicidin S, however, cyclosemigramicidin S showed no activity in response to any of the microorganisms tested.