Ra. Breitenmoser et H. Heimgartner, Scope and limitation of the acid-catalyzed isomerization of Aib-containingthiopeptides, HELV CHIM A, 84(4), 2001, pp. 786-796
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.