Abstract: | Derivatives of gramicidin S (GS) and its mono- and di-d-cyclohexylalanine (d-Cha) analogs possessing various protecting groups on Orn side chains were prepared. 1H NMR spectra of the unsymmetrically protected analogs Orn(X)2,Orn(X )2 ,d-Cha4]GS were similar to the composites of the spectra of the symmetrical derivatives Orn(X)2,2 ,d-Cha4,4 ]GS and Orn(X )2,2 ]GS, revealing the proximity of the protecting groups of N H of Orn residues at the 2 and 2 positions to the side chains of d-Phe (or d-Cha) residues at the 4 and 4 positions, respectively. The results indicated the presence of H-bonds between the N H of Orn and the carbonyl of d-Phe residues in the i i + 2 sense and not in i i – 3, which was also supported by the ROESY analysis. The substantially strong H-bonds can explain the observed resistance of the urethane NH of the Orn side chains in the GS derivatives to the N-methylation with CH3I–Ag2O in DMF. |