Die Synthese von Gramicidin S

Abstract

AbstractThe synthesis of gramicidin S10), a peptide antibiotic from Bac. brevis, is described in detail. The decapeptide derivative trityl · (Val‐p‐Tos · Orn‐Leu‐Phe‐Pro)2· OCH3 (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 H2O (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 dihydrochloride21) respectively. This proves the structure of gramicidin S as cyclic decapeptide, and constitutes the first synthesis of a naturally occurring cyclic peptide.