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 medium-sized cyclic depsipeptides and peptides derived from salicylic acids 6 and anthranilic acid 19, respectively (Schemes2-4 and 5, resp.). The combination of the ‘azirine/oxazolone method’ for the synthesis of linear peptides containing alpha,alpha-disubstituted alpha-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 to 25). Larger rings proved to be extremely sensitive to hydrolysis.

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