Die Synthese von Gramicidin S

The synthesis of gramicidin S 10 ), a peptide antibiotic from Bac. brevis , is described in detail. The decapeptide derivative trityl · (Val‐p‐Tos · Orn‐Leu‐Phe‐Pro) 2 · OCH 3 ( L ‐ L ‐ L ‐ D ‐ L ) 2 is converted to the corresponding p‐nitrophenyl ester, the trityl group is removed selectively, and the resulting product is cyclised to cyclo‐(Val‐p‐Tos ·Orn‐Leu‐Phe‐Pro) 2 · 2 H 2 O ( L ‐ L ‐ L ‐ D ‐ L ) 2 . Sodium in liquid ammonia removes the p‐toluene‐sulfonyl groups, and cyclo‐(Val‐Orn‐Leu‐Phe‐Pro) 2 ( L ‐ L ‐ L ‐ D ‐ L ) 2 is obtained as dihydrochloride (I). The cyclic products are purified by countercurrent distribution and identified with gramicidin S ditosylate and gramicidin S dihydrochloride 21 ) respectively. This proves the structure of gramicidin S as cyclic decapeptide, and constitutes the first synthesis of a naturally occurring cyclic peptide.