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Formation of 1,3‐Thiazol‐5(4 H )‐imines and 1,3‐Oxazol‐5(4 H )‐imines in Aib‐Containing Thiopeptides
Author(s) -
Breitenmoser Roland A.,
Linden Anthony,
Heimgartner Heinz
Publication year - 2002
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 - 10.1002/1522-2675(200204)85:4<990::aid-hlca990>3.0.co;2-6
Subject(s) - chemistry , imine , azirine , tripeptide , thioamide , moiety , isomerization , reagent , stereochemistry , combinatorial chemistry , peptide , medicinal chemistry , organic chemistry , catalysis , ring (chemistry) , biochemistry
When tripeptides of type Axx t ‐Aib‐Axx‐OH were coupled with amino acid methyl esters by means of commonly used coupling reagents, the formation of 1,3‐thiazol‐5(4 H )‐imines and 1,3‐oxazol‐5(4 H )‐imines was observed. With the aim of understanding which structure elements are required for this reaction, several model peptides have been prepared according to our recently described methodology, a modification of the ‘azirine/oxazolone method', followed by selective isomerization of the peptide thioamides. In addition, attempts to prepare peptides that contain more than one C=S group by the same methodology also led to the formation of 1,3‐thiazol‐5(4 H )‐imine‐containing derivatives. An additional C=S group can be introduced into the peptide, when the 1,3‐thiazol‐5(4 H )‐imines were treated with H 2 S, although mixtures of epimers were obtained. The structures of an endothiohexapeptide, two 1,3‐thiazol‐5(4 H )‐ones, and two peptides containing a 1,3‐thiazol‐5(4 H )‐imine moiety have been established by X‐ray crystal‐structure analysis.