SYNTHESIS OF CYCLIC DEPSIPEPTIDES AND PEPTIDES VIA DIRECT AMIDE CYCLIZATION

The 2,2-disubstituted 2H-azirin-3-amines 7 (2.2-disubstituted 3-amino- 2H-azirines) were used as amino-acid synthons in the preparation of me dium-sized cyclic depsipeptides and peptides derived from salicylic ac ids 6 and anthranilic acid 19, respectively (Schemes 2-4 and 5, reap.) . The combination of the 'azirine/oxazolone method' for the synthesis of linear peptides containing alpha,alpha-disubstitutcd alpha-amino ac ids and the acid-catalyzed amide cyclization in DMF at 60 degrees prov ed to be an excellent preparative route to ten-membered cyclic depsipe ptides and peptides. In the case of the anthranilic-acid derivative, a transannular ring-closure reaction was observed (24 --> 25). Larger r ings proved to be extremely sensitive to hydrolysis.