Synthesis of Cyclic Depsipeptides and Peptides via Direct Amide Cyclization

The 2,2‐disubstituted 2 H ‐azirin‐3‐amines 7 (2,2‐disubstituted 3‐amino‐2 H ‐azirines) were used as amino‐acid synthons in the preparation of medium‐sized cyclic depsipeptides and peptides derived from salicylic acids 6 and anthranilic acid 19 , respectively ( Schemes 2‐‐4 and 5 , resp.). The combination of the ‘azirine/oxazolone method’ for the synthesis of linear peptides containing α,α‐disubstituted α‐amino acids and the acid‐catalyzed amide cyclization in DMF at 60° proved to be an excellent preparative route to ten‐membered cyclic depsipeptides and peptides. In the case of the anthranilic‐acid derivative, a transannular ring‐closure reaction was observed ( 24 → 25 ). Larger rings proved to be extremely sensitive to hydrolysis.