Direct synthesis of gramicidin S via cyclization of pentapeptide active-esters without protecting delta-amino group of Orn residue.

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Five linear pentapeptide succinimide esters (-ONSu) related to gramicidin S(GS), in which Val, Orn, Leu, D-Phe, and Pro residue occupys at C-terminal and delta-amino group of Orn residue is not protected, is cyclized in order to investigate an Influence of delta-amino group of Orn residue on the cyclization. The cyclization of H-D-Phe-Pro-Val-Orn-Leu-ONSu in pyridine at 25 ﾟC (concentration of peptide in pyridine : 3 x 10^<-3> M) produced semi-GS (cyclic monomer) and GS (cyclic dimer) in a yield of 15 and 38 %, respectively. On the other hand, the cyclization of other pentapeptide-ONSu gave mainly cyclic pentapeptides involving amide bond between the carboxyl group of amino acid residue at C-terminal of each active ester and the delta-amino group of Orn residue, but did not any amount of GS. From these studies, it was found that in the cyclization of pentapeptlde-ONSu without protecting delta-amino group of Orn residue, the special sequence is necessary to synthesize directly GS by the cyclic dimerization and is identical with the linear pentapeptide precusor(D-Phe-Pro-Val-Orn-Leu)used in the biosynthesis of natural GS. A simular result was obtained in the study of the cyclization of H-D-Phe-Pro-D-Tyr-Val-Orn-Leu-ONSu related to gratisn.