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Synthesis of Cyclic Depsipeptides and Peptides via Direct Amide Cyclization
Author(s) -
Villalgordo José M.,
Heimgartner Heinz
Publication year - 1997
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.19970800312
Subject(s) - chemistry , depsipeptide , synthon , oxazolone , anthranilic acid , azirine , amide , cyclic peptide , stereochemistry , ring (chemistry) , hydrolysis , amino acid , derivative (finance) , peptide , combinatorial chemistry , organic chemistry , biochemistry , financial economics , economics
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.