Scope and limitation of the acid-catalyzed isomerization of Aib-containingthiopeptides

The use of amino thio S-acids in thr 'azirine/oxazolone method' and a novel isomerization ion led to Aib-containing endothiopeptides. With the aim of generalizing this method, a variety of Aib-containing dipeptide thioanilide s have been prepared. Bq their treatment with ZnCl2 in AcOH, followed by HC l-saturated AcOH, the C=S group was shifted from the last to the penultimat e amino acid in high yield and without epimerization. As this methodology i s very useful for the specific introduction of a thioamide group. it was ex tended to Aib-containing tripeptides. In addition. it could he shown that a mechanism via spirocyclic intermediates (cf. Scheme 4) is most likely for this isomerization. To establish the proposed neighboring-group participati on of the N-acyl group, model dipeptide thioanilides containing no N-termin al C - O group were synthesized. These derivatives did not undergo rearrang ement.