Cylic Peptides

Two diastereomeric cyclic tetrapeptides with a sequence of cyclo (‐D (and L)‐Tyr (Me)‐L‐Ile‐L‐Pro‐L‐Leu‐) (ID and IL) have been synthesized, which are simplified analogs of a phytotoxic peptide Cyl‐2, and contain an L‐proline and an L‐leucine residue in place of an L‐pipecolic acid and a 2‐amino‐8‐oxo‐9,10‐epoxydecanoic acid residue, respectively, in Cyl‐2. The cyclization of the H‐D‐Tyr(Me)‐L‐Ile‐L‐Pro‐L‐Leu‐ONSu proceeded smoothly to give ID in excellent yield (50%), but the cyclization of H‐L‐Tyr(Me)‐L‐Ile‐L‐Pro‐L‐Leu‐ONSu gave IL in much lower yield (10%). Based on the results of 1H‐ and 13C‐n.m.r. studies, differential N‐methylation and model buildings of ID, the backbone structure of ID has been proposed to be a unique trans‐trans‐cis‐trans conformation, the L‐Ile‐L‐Pro bond being cis.